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A cross-sectional study was conducted on 92 female donkeys. Blood samples were collected, and the following parameters were evaluated: red blood cell (RBC), white blood cell, neutrophil, lymphocyte, monocyte (MON), eosinophil (EOS) and basophil counts, hemoglobin concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and the hematocrit (HCT), alanine aminotransferase (GPT), aspartate aminotransferase, total proteins, γ-glutamyl-transferase, alkaline phosphatase, creatinine, urea, and blood urea nitrogen and electrophoretic profile. Age (≥2 years ≤ 3 [very young], >3 years ≤ 10 [young], and >10 years ≤ 17 [adult]) and lactation (early lactation [≤3 months], middle [>3 months ≤ 6], and late lactation [>6 months]). Groups were independently analyzed using one-way analysis of variance or Kruskal–Wallis (post hoc test: Bonferroni's or Dunn's multiple test) tests; P was set as

The objective was to determine the effect of stockpiled forage type and protein supplementation on VFA production, serum metabolites, and heifer BW. Over 2 yr, spring-born, crossbred heifers (n = 45) were stratified by BW at weaning and randomly assigned to 1 of 3 forage treatments: 1) endophyte-infected tall fescue (TF; Festuca arundinacea), 2) big bluestem (Andropogon gerardi Vitman) and indiangrass (Sorghastrum nutans L.) combination (BI), or 3) switchgrass (SG; Panicum virgatum L.). Forage treatments were then randomly assigned to receive 1 of 2 supplement types: 1) 0.68 kg·heifer-1·d-1 of dried distiller's grains with solubles (DDGS; 28% CP, 74% RUP, and 88% TDN) or 2) 0.22 kg·heifer-1·d-1 of blood meal and fish meal (BF; 72.5% CP, 67.5% RUP, and 69.5% TDN), resulting in a 3 × 2 factorial arrangement of treatments. Treatments were initiated every year in January and terminated in April at the onset of a 60-d breeding season. Body weights and serum samples were collected approximately every 28 d from initiation of grazing until breeding. Serum glucose concentrations were greater (P = 0.05) for heifers grazing SG. Circulating NEFA concentrations were greater (P = 0.04) in TF heifers. Serum urea N (SUN) was not influenced (P = 0.37) by forage type. Ruminal acetate concentration and acetate:propionate ratio were greater (P = 0.04) in heifers grazing SG pastures. Heifer BW change from January to February and overall BW change were greater (P < 0.01) for TF heifers. However, BW change from March to April was not different (P = 0.84) among forage types. Serum glucose and SUN concentrations exhibited (P < 0.05) supplement type × sampling time interactions. Ruminal acetate tended to be greater (P = 0.09) and butyrate concentrations were greater (P < 0.01) for BF-supplemented heifers. The acetate:propionate ratio was not influenced (P = 0.15) by supplement type. Supplement type did not influence (P > 0.13) BW or BW change from January to February and January to April; however, heifers fed DDGS gained (P = 0.03) more BW from March to April. Heifer BW change from February to March exhibited (P < 0.05) a forage type × supplement interaction with BF heifers gaining more BW on BI pastures than DDGS heifers. Overall, developing heifers on low-quality native forages initially delayed BW gain; however, heifers seemed to quickly adapt to the lower-quality forage, resulting in similar BW gains in March and April. [ABSTRACT FROM AUTHOR]

Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This cross-sectional study investigates the methicillin-resistant Staphylococcus aureus (MRSA): its prevalence, antimicrobial resistance, and molecular characteristics in healthy swine populations in central Portugal. A total of 213 samples were collected from pigs on twelve farms, and MRSA prevalence was assessed using selective agar plates and confirmed via molecular methods. Antimicrobial susceptibility testing and whole genome sequencing (WGS) were performed to characterize resistance profiles and genetic determinants. Among the 107 MRSA-positive samples (83.1% prevalence), fattening pigs and breeding sows exhibited notably high carriage rates. The genome of 20 isolates revealed the predominance of the ST398 clonal complex, with diverse spa types identified. Antimicrobial susceptibility testing demonstrated resistance to multiple antimicrobial agents, including penicillin, cefoxitin, and tetracycline. WGS analysis identified a diverse array of resistance genes, highlighting the genetic basis of antimicrobial resistance. Moreover, virulence gene profiling revealed the presence of genes associated with pathogenicity. These findings underscore the significant prevalence of MRSA in swine populations and emphasize the need for enhanced surveillance and control measures to mitigate zoonotic transmission risks. Implementation of prudent antimicrobial use practices and targeted intervention strategies is essential to reducing MRSA prevalence and safeguarding public health. Continued research efforts are warranted to elucidate transmission dynamics and virulence potential, ultimately ensuring food safety and public health protection.

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA monitoring in wastewater has become an important tool for Coronavirus Disease 2019 (COVID-19) surveillance. Grab (quantitative) and passive samples (qualitative) are two distinct wastewater sampling methods. Although many viral concentration methods such as the usage of membrane filtration and skim milk are reported, these methods generally require large volumes of wastewater, expensive lab equipment, and laborious processes., Methods: The objectives of this study were to compare two workflows (Nanotrap ® Microbiome A Particles coupled with MagMax kit and membrane filtration workflows coupled with RNeasy kit) for SARS-CoV-2 recovery in grab samples and two workflows (Nanotrap ® Microbiome A Particles and skim milk workflows coupled with MagMax kit) for SARS-CoV-2 recovery in Moore swab samples. The Nanotrap particle workflow was initially evaluated with and without the addition of the enhancement reagent 1 (ER1) in 10 mL wastewater. RT-qPCR targeting the nucleocapsid protein was used for detecting SARS-CoV-2 RNA., Results: Adding ER1 to wastewater prior to viral concentration significantly improved viral concentration results ( P < 0.0001) in 10 mL grab and swab samples processed by automated or manual Nanotrap workflows. SARS-CoV-2 concentrations in 10 mL grab and Moore swab samples with ER1 processed by the automated workflow as a whole showed significantly higher ( P < 0.001) results than 150 mL grab samples using the membrane filtration workflow and 250 mL swab samples using the skim milk workflow, respectively. Spiking known genome copies (GC) of inactivated SARS-CoV-2 into 10 mL wastewater indicated that the limit of detection of the automated Nanotrap workflow was ~11.5 GC/mL using the RT-qPCR and 115 GC/mL using the digital PCR methods., Discussion: These results suggest that Nanotrap workflows could substitute the traditional membrane filtration and skim milk workflows for viral concentration without compromising the assay sensitivity. The manual workflow can be used in resource-limited areas, and the automated workflow is appropriate for large-scale COVID-19 wastewater-based surveillance., Competing Interests: RBarb, BL, RBarc, and CC were employed by Ceres Nanosciences, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Guo, Cavallo, Cantrell, Hilton, Nguyen, Long, Dunbar, Barbero, Barclay, Sablon, Wolfe, Lepene and Moe.)

Climate teleconnections (CT) remotely influence weather conditions in many regions on Earth, entailing changes in primary drivers of fire activity such as vegetation biomass accumulation and moisture. We reveal significant relationships between the main global CTs and burned area that vary across and within continents and biomes according to both synchronous and lagged signals, and marked regional patterns. Overall, CTs modulate 52.9% of global burned area, the Tropical North Atlantic mode being the most relevant CT. Here, we summarized the CT-fire relationships into a set of six global CT domains that are discussed by continent, considering the underlying mechanisms relating weather patterns and vegetation types with burned area across the different world's biomes. Our findings highlight the regional CT-fire relationships worldwide, aiming to further support fire management and policy-making., (© 2023. The Author(s).)

Infectious uveitis is a sight-threatening infection commonly caused by herpesviruses. Vitreous humor is often collected for molecular confirmation of the causative agent during vitrectomy and mixed in large volumes of buffered saline, diluting the pathogen load. Here, we explore affinity-capture hydrogel particles (Nanotrap ® ) to concentrate low abundant herpesviruses from diluted vitreous. Simulated samples were prepared using porcine vitreous spiked with HSV-1, HSV-2, VZV and CMV at 10 5 copies/mL. Pure undiluted samples were used to test capturing capability of three custom Nanotrap particles (red, white and blue) in a vitreous matrix. We found that all particles demonstrated affinity to the herpesviruses, with the Red Particles having both good capture capability and ease of handling for all herpesviruses. To mimic diluted vitrectomy specimens, simulated-infected vitreous were then serially diluted in 7 mL TE buffer. Diluted samples were subjected to an enrichment protocol using the Nanotrap Red particles. Sensitivity of pathogen detection by qPCR in diluted vitreous increased anywhere between 2.3 to 26.5 times compared to non-enriched specimens. This resulted in a 10-fold increase in the limit of detection for HSV-1, HSV-2 and VZV. These data demonstrated that Nanotrap particles can capture and concentrate HSV-1, HSV-2, VZV and CMV in a vitreous matrix.

Different studies have suggested that during speech processing readers with dyslexia present atypical levels of neural entrainment as well as atypical functional hemispherical asymmetries in comparison with typical readers. In this study, we evaluated these differences in children and the variation with age before and after starting with formal reading instruction. Synchronized neural auditory processing activity was quantified based on auditory steady-state responses (ASSRs) from EEG recordings. The stimulation was modulated at syllabic and phonemic fluctuation rates present in speech. We measured the brain activation patterns and the hemispherical asymmetries in children at three age points (5, 7, and 9 years old). Despite the well-known heterogeneity during developmental stages, especially in children and in dyslexia, we could extract meaningful common oscillatory patterns. The analyses included (1) the estimations of source localization, (2) hemispherical preferences using a laterality index, measures of neural entrainment, (3) signal-to-noise ratios (SNRs), and (4) connectivity using phase coherence measures. In this longitudinal study, we confirmed that the existence of atypical levels of neural entrainment and connectivity already exists at pre-reading stages. Overall, these measures reflected a lower ability of the dyslectic brain to synchronize with syllabic rate stimulation. In addition, our findings reinforced the hypothesis of a later maturation of the processing of beta rhythms in dyslexia. This investigation emphasizes the importance of longitudinal studies in dyslexia, especially in children, where neural oscillatory patterns as well as differences between typical and atypical developing children can vary in the span of a year., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Granados Barbero, Ghesquière and Wouters.)

Phytotherapy is based on the use of plants to prevent or treat human and animal diseases. Recently, the use of essential oils and polyphenol-enriched extracts is also rapidly increasing in the aquaculture sector as a means of greater industrial and environmental sustainability. Previous studies assessed the antibacterial and antiparasitic effects of these bioactive compounds on fish. However, studies on the modulation of oxidative stress biomarkers are still scant to date. Thus, in this study, the modulation of antioxidant defense against oxidative stress exerted by fish diets supplemented with a basil supercritical extract (F1-BEO) was assessed in rainbow trout Oncorhynchus mykiss . The F1-BEO extracted with supercritical fluid extraction was added to the commercial feed flour (0.5, 1, 2, 3% w / w ) and mixed with fish oil to obtain a suitable compound for pellet preparation. Fish were fed for 30 days. The levels of stress biomarkers such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, glyoxalase I, glyoxalase II, lactate dehydrogenase, glutathione and malondialdehyde showed a boost in the antioxidant pathway in fish fed with a 0.5% F1-BEO-supplemented diet. Higher F1-BEO supplementation led to a failure of activity of several enzymes and the depletion of glutathione levels. Malondialdehyde concentration suggests a sufficient oxidative stress defense against lipid peroxidation in all experimental groups, except for a 3% F1-BEO-supplemented diet (liver 168.87 ± 38.79 nmol/mg prot; kidney 146.86 ± 23.28 nmol/mg prot), compared to control (liver 127.76 ± 18.15 nmol/mg prot; kidney 98.68 ± 15.65 nmol/mg prot). Our results suggest supplementing F1-BEO in fish diets up to 0.5% to avoid potential oxidative pressure in farmed trout.

Modeling wildfire activity is crucial for informing science-based risk management and understanding the spatiotemporal dynamics of fire-prone ecosystems worldwide. Models help disentangle the relative influences of different factors, understand wildfire predictability, and provide insights into specific events. Here, we develop Firelihood, a two-component, Bayesian, hierarchically structured, probabilistic model of daily fire activity, which is modeled as the outcome of a marked point process: individual fires are the points (occurrence component), and fire sizes are the marks (size component). The space-time Poisson model for occurrence is adjusted to gridded fire counts using the integrated nested Laplace approximation (INLA) combined with the stochastic partial differential equation (SPDE) approach. The size model is based on piecewise-estimated Pareto and generalized Pareto distributions, adjusted with INLA. The Fire Weather Index (FWI) and forest area are the main explanatory variables. Temporal and spatial residuals are included to improve the consistency of the relationship between weather and fire occurrence. The posterior distribution of the Bayesian model provided 1,000 replications of fire activity that were compared with observations at various temporal and spatial scales in Mediterranean France. The number of fires larger than 1 ha across the region was coarsely reproduced at the daily scale, and was more accurately predicted on a weekly basis or longer. The regional weekly total number of larger fires (10-100 ha) was predicted as well, but the accuracy degraded with size, as the model uncertainty increased with event rareness. Local predictions of fire numbers or burned areas also required a longer aggregation period to maintain model accuracy. The estimation of fires larger than 1 ha was also consistent with observations during the extreme fire season of the 2003 unprecedented heat wave, but the model systematically underrepresented large fires and burned areas, which suggests that the FWI does not consistently rate the actual danger of large fire occurrence during heat waves. Firelihood enabled a novel analysis of the stochasticity underlying fire hazard, and offers a variety of applications, including fire hazard predictions for management and projections in the context of climate change., (© 2021 by the Ecological Society of America.)

Twelve biochemical parameters were measured in serum blood samples from rainbow trout ( Oncorhynchus mykiss ) maintained under controlled conditions. Forty-five samples were taken every 3 months (T1-T4) over the course of one year to define baseline values. The effect of fish total weight (TW) was also evaluated. Principal component analysis showed a clear separation between T4 and T1, and T2 and T3, indicating an increase in certain biochemical parameters with weight. Linear regression analysis showed how TW significantly explained 11-67% of the variability observed for nine parameters out of 12. Pearson's correlation matrix showed a significant positive correlation ( p < 0.05) between TW and albumin, alkaline phosphatase, alanine-aminotransferase, creatinine, gamma-glutamyl transferase, magnesium, phosphorus and total protein. Furthermore, significant correlations ( p < 0.05) between the majority of the biochemical parameters were found, indicating that growth can influence several parameters at the same time. The present study provides several useful baseline values for assessing the health of O. mykiss , indicating that fish weight is an important factor for interpreting the blood biochemical profile.

One of the ways to make cost-competitive electricity, from concentrated solar thermal energy, is increasing the thermoelectric conversion efficiency. To achieve this objective, the most promising scheme is a molten salt central receiver, coupled to a supercritical carbon dioxide cycle. A key element to be developed in this scheme is the molten salt-to-CO 2 heat exchanger. This paper presents a heat exchanger design that avoids the molten salt plugging and the mechanical stress due to the high pressure of the CO 2 , while improving the heat transfer of the supercritical phase, due to its compactness with a high heat transfer area. This design is based on a honeycomb-like configuration, in which a thermal unit consists of a circular channel for the molten salt surrounded by six smaller trapezoidal ducts for the CO 2 . Further, an optimization based on the exergy destruction minimization has been accomplished, obtained the best working conditions of this heat exchanger: a temperature approach of 50 °C between both streams and a CO 2 pressure drop of 2.7 bar.

Lactococcosis is a fish disease of major concern in Mediterranean countries caused by Lactococcus garvieae . The most susceptible species is the rainbow trout ( Oncorhynchus mykiss ), suffering acute disease associated with elevated mortalities compared to other fish species. References reported that other salmonids are also susceptible to the disease, but no mortality outbreak has been described to date. The aim of this study was to present a mortality outbreak that occurred in brook trout ( Salvelinus fontinalis ) farmed in northwestern Italy during the summer of 2018. Fish exhibited clinical signs, such as exophthalmos, diffused hemorrhages localized in the ocular zone, hemorrhagic enteritis, and enlarged spleen. L. garvieae was isolated in all fish. Molecular and epidemiological characterization of the isolates, through Pulsed Field Gel Electrophoresis (PFGE), confirmed the initial hypothesis of water as vehicle of infection favoring transmission between rainbow trout farmed in upstream compartments and brook trout located in downstream tanks. Moreover, several environmental conditions affected and promoted the outbreak, among them the high-water temperature, which probably induced a physiological stress in brook trout, being way above the optimal temperature for this species, increasing the susceptibility to infection.

Endophthalmitis is a rare, but serious, intravitreal inflammatory disorder that can arise after cataract surgery. The intracameral injection of 1 mg cefuroxime (CEF) followed by three-times daily antibiotic topical administration for a week is generally recognized as the routine method of prophylaxis after cataract surgery. This procedure is controversial because of both the low efficacy and the low adherence to therapy by elderly patients. A unique slow release antibiotic intravitreal injection could solve these problems. The objective of the present study was to design ophthalmic nanocomposite delivery systems based on in situ gelling formulations that undergo sol-to-gel transition upon change in temperature to prolong the effect of CEF. Oil in water (O/W) microemulsion (µE) and solid lipid nanoparticles (SLN), obtained with an innovative formulation technology called cold microemulsion dilution , were evaluated as ocular drug delivery systems for CEF. Drug entrapment efficiency up to 80% was possible by esterifying CEF with 1-dodecanol to obtain dodecyl-CEF (dCEF). Both dCEF-loaded SLN and µE were then added with Pluronic®F127 (20% w / v ) to obtain a nanocomposite hydrogel-based long acting system. The prepared thermosensitive formulations were evaluated for their physical appearance, drug content, gelation temperature, injectability and rheological properties, in vitro release studies and stability studies. Moreover, cell proliferation assays on human retinal pigment epithelial ARPE-19 cells were performed to evaluate the influence of this innovative system on the cellular viability. In addition, minimal inhibitory concentration (MIC) was assessed for both CEF and dCEF, revealing the need of dCEF hydrolysis for the antimicrobial activity. Although further experimental investigations are required, the physico-chemical characterization of the nanocomposite hydrogels and the preliminary in vitro release studies highlighted the potential of these systems for the sustained release of CEF.

Urban parks are green areas of cities where families and children spend hours outside. Turtles often inhabit urban parks. However, even if the animals seem harmless, they may serve as both reservoirs or accidental hosts for different serotypes of Leptospira spp. Leptospira spp. is a waterborne zoonotic bacterium relevant for public health. Reptiles and amphibians may play a role in the epidemiology, transmission, and persistence of Leptospira spp. In the present study, we observed the presence of anti-leptospiral agglutinins in a group of freshwater turtles ( Trachemys scripta ) captured in three urban ponds of the metropolitan city of Turin, Italy., Competing Interests: The authors declare no conflict of interest.

Background: The breeding of lactating donkeys is increasing in Western Europe; with it the evaluation of body condition is growing in importance since it is considered a key principle for their welfare. However, assessment of body condition is a complex task, since several factors are involved. The aim of the present study is to investigate which animal-based indicators are the most reliable to describe the body condition of lactating donkeys. For this purpose, new animal-based indicators, which are easy to measure in field conditions (including body measurements, fatty neck score (FNS), dental score), are recorded and their relationship with BCS (a proxy measure for overall adiposity) was assessed. The ones that reveal an association with the BCS are included in an integrated principal component analysis to understand which are the most related to BCS., Methods: Fifty-three healthy lactating donkeys of various breeds, including 7 Martina Franca, 10 Ragusano, 2 Romagnolo and 34 crossbreeds, were evaluated. The animal-based indicators that were recorded were: length (OP, olecranon tuber-pinbone and SH, shoulder-hip), heart girth (HG), abdominal circumference (AC), neck length (NL), neck height (NH) and neck thickness (NT) at 0.50 and neck circumference (NC) at 0.25, 0.50 and 0.75, body condition score (BCS) and fatty neck score (FNS). The owners' evaluation of the BCS was also considered. A dental assessment was performed and the month of lactation and age of each animal was recorded., Results: No correlation was found between BCS and the other morphometric body measurements. On the contrary the FNS was correlated with the morphometric measurements of the neck (positive correlation to 0.50 NH and 0.50 NT, 0.50 NC, 0.75 mean NC, and negative correlation to the mean NC:NH and mean NC:NT, 0.50 NC:NT and 0.50 NC:NH ratios). A significant inverse relationship was identified between BCS and dental score. A Principal Component analysis (PCA) separated the BCS classes on the first principal component (PC1). PC1 revealed a meaningful positive correlation between the BCS and the neck measurements (NT, NH and FNS), with high positive loadings, while a negative correlation was found for dental abnormalities. The owners' evaluation of BCS was different from the expert evaluator' assessment, since they tended to give higher score that was slightly but significantly correlated to AC., Discussion: A new scoring system, called Fatty Neck Score (FNS), has been proposed for the judgement of the adiposity status of donkey neck. The results suggest that caregivers might use the proposed animal based indicators (BCS, FNS and dental scores) together as a tool for the evaluation of the body condition of lactating donkeys. Our findings highlight that caregivers need to be trained in order to be able to properly record these indicators. Ultimately use of these indicators may help to improve the welfare of lactating donkeys., Competing Interests: The authors declare there are no competing interests.

Purpose: Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel belonging to the transient receptor potential family, and it is expressed in different neoplastic tissues. Its activation is associated with regulation of cancer growth and progression. The aim of this research was to study the expression and pharmacological characteristics of TRPV1 in cells derived from human breast cancer MCF-7 cells., Methods: TRPV1 presence was assessed by binding studies and Western blotting. Receptor binding characteristics were evaluated through competition assays, while 3-(4,5-dimethylthiazol-2-yl)-2,5,-dipheyltetrazolium bromide reduction assays were performed to confirm an early hypothesis regarding the modulation of cancer cell proliferation. The functionality of TRPV1 was evaluated by measuring Ca(2+) uptake in the presence of increasing concentrations of TRPV1 agonists and antagonists., Results: Binding studies identified a single class of TRPV1 (Bmax 1,492±192 fmol/mg protein), and Western blot showed a signal at 100 kDa corresponding to the molecular weight of human TRPV1. Among the different tested agonists and antagonists, anandamide (Ki: 2.8×10(-11) M) and 5-iodoresiniferatoxin (5-I-RTX) (Ki: 5.6×10(-11) M) showed the highest degrees of affinity for TRPV1, respectively. All tested TRPV1 agonists and antagonists caused a significant (p<0.05) decrease in cell growth rate in MCF-7 cells. For agonists and antagonists, the efficacy of tested compounds displayed the following rank order: resiniferatoxin>anandamide>capsaicin and 5-I-RTX=capsazepine, respectively., Conclusion: These data indicate that both TRPV1 agonists and antagonists induce significant inhibition of MCF-7 cell growth. Even though the mechanisms involved in the antiproliferative effects of TRPV1 agonists and antagonists should be further investigated, it has been suggested that agonists cause desensitization of the receptor, leading to alteration in Ca(2+)-influx regulation. By contrast, antagonists cause a functional block of the receptor with consequent fatal dysregulation of cell homeostasis.

Objective: Only a limited proportion of patients needing pharmacological control of portal hypertension are hemodynamic responders to propranolol. Here we analyzed the effects of zolmitriptan on portal pressure and its potential interaction with propranolol., Methods: ZOLMITRIPTAN, PROPRANOLOL OR BOTH WERE TESTED IN TWO RAT MODELS OF PORTAL HYPERTENSION: common bile duct ligation (CBDL) and CCl4-induced cirrhosis. In these animals we measured different hemodynamic parameters including portal venous pressure, arterial renal flow, portal blood flow and cardiac output. We also studied the changes in superior mesenteric artery perfusion pressure and in arterial wall cAMP levels induced by zolmitriptan, propranolol or both. Moreover, we determined the effect of splanchnic sympathectomy on the response of PVP to zolmitriptan., Results: In both models of portal hypertension zolmitriptan induced a dose-dependent transient descent of portal pressure accompanied by reduction of portal flow with only slight decrease in renal flow. In cirrhotic rats, splanchnic sympathectomy intensified and prolonged zolmitriptan-induced portal pressure descent. Also, propranolol caused more intense and durable portal pressure fall when combined with zolmitriptan. Mesenteric artery perfusion pressure peaked for about 1 min upon zolmitriptan administration but showed no change with propranolol. However propranolol enhanced and prolonged the elevation in mesenteric artery perfusion pressure induced by zolmitriptan. In vitro studies showed that propranolol prevented the inhibitory effects of β2-agonists on zolmitriptan-induced vasoconstriction and the combination of propranolol and zolmitriptan significantly reduced the elevation of cAMP caused by β2-agonists., Conclusion: Zolmitriptan reduces portal hypertension and non-selective beta-blockers can improve this effect. Combination therapy deserves consideration for patients with portal hypertension failing to respond to non-selective beta-blockers.

Familial acromegaly may occur as an isolated pituitary disorder or as a feature of hereditary syndromes, such as multiple endocrine neoplasia type 1 (MEN1) or the Carney complex. Herein, we characterized a newly identified kindred with isolated acromegaly and searched for germline mutation in genes that have been associated with endocrine tumors [i.e. MEN1, Gs alpha (GNAS1), and Gi2 alpha (GNAI2)], as well as the GHRH receptor (GHRH-R) gene. Genomic DNA was used to amplify exons 2-10 of MEN1, followed by dideoxy fingerprinting mutation analysis and direct sequencing. The GHRH-R gene was analyzed via direct sequencing of PCR-amplified fragments representing the coding exons and intron-exon junctions. To exclude mutation at hot spot areas of GNAS1 and GNAI2, exons 8 and 9 of GNAS1 and exons 5 and 6 of GNAI2 were amplified and screened for mutation via denaturing gradient gel electrophoresis. No mutations were detected in any of the four genes. The present data extend prior reports of the absence of mutation in MEN1, GHRH-R, and GNAS1 and describe the first family with isolated acromegaly in which germline mutation in GNAI2 has been searched.