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1.
Int J Biometeorol ; 67(11): 1853-1868, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37718383

ABSTRACT

Aerobiological studies are still scarce in northwestern Mexico where allergenic pollen have great impacts on health. Current global pollution and climate change problems are closely related to many allergic diseases, enhancing the need to continue researching these issues and improve life quality. This study provides the first Pollen Calendar for Hermosillo, Sonora, México. Airborne pollen were continuously collected for 5 years (2015-2019). The standardized methodology with a Hirst-type spore trap proposed for global aerobiological studies was used. Weather data were also taken from a station located in the city and used to explore correlations between climate and airborne pollen concentrations in different seasons. The most important pollen taxa recorded in air belongs to herbaceous pollen, such as Poaceae, Ambrosia, Asteraceae, Chenopodiaceae-Amaranthaceae, and some shrub trees typical of this arid region, such as Nyctaginaceae, Prosopis, Parkinsonia, and Fabaceae. The most critical herbaceous pollen related to allergies have a long mean pollen season throughout the years, and the most critical periods with high pollen concentration in air occur in two seasons, spring (March-April) and summer-fall (August-October). In these 5 years, the correlation analyses for these two peaks indicate that a link exists between pollen in the air and decreases in precipitation and temperatures, and an increase in relative humidity. An inter-annual variability in pollen concentrations was recorded related to different weather conditions. Although pollen calendars are location-specific, they are useful for future research on biological air quality scenarios in different cities. Using this standardized method for other regions can provide pollen calendars that have been proven clinically important in allergic disease management worldwide.

2.
Phys Chem Chem Phys ; 22(37): 21108-21118, 2020 Sep 30.
Article in English | MEDLINE | ID: mdl-32954397

ABSTRACT

To gain better understanding of the stabilizing interactions between metal ions and DNA quadruplexes, dispersion-corrected density functional theory (DFT-D) based calculations were performed on double-, triple- and four-layer guanine tetrads interacting with alkali metal cations. All computations were performed in aqueous solution that mimics artificial supramolecular conditions where guanine bases assemble into stacked quartets as well as biological environments in which telomeric quadruplexes are formed. To facilitate the computations on these significant larger systems, optimization of the DFT description was performed first by evaluating the performance of partial reduced basis sets. Analysis of the stabilizing interactions between alkali cations and the DNA bases in double and triple-layer guanine quadruplex DNA reproduced the experimental affinity trend of the order Li+< Rb+ < Na+ < K+. The desolvation and the size of alkali metal cations are thought to be responsible for the order of affinity. Nevertheless, for the alkali metal cation species individually, the magnitude of the bond energy stays equal for binding as first, second or third cation in double, triple and four-layer guanine quadruplexes, respectively. This is the result of an interplay between a decreasingly stabilizing interaction energy and increasingly stabilizing solvation effects, along the consecutive binding events. This diminished interaction energy is the result of destabilizing electrostatic repulsion between the hosted alkali metal cations. This work emphasizes the stabilizing effect of aqueous solvent on large highly charged biomolecules.


Subject(s)
DNA/chemistry , G-Quadruplexes , Guanine/chemistry , Metals, Alkali/chemistry , DNA/genetics , Density Functional Theory , Models, Chemical , Thermodynamics
3.
J Endocrinol Invest ; 43(10): 1447-1452, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32239476

ABSTRACT

BACKGROUND: Assessing adherence to growth hormone (GH) is challenging. The Easypod™ connect device delivers pre-set doses of recombinant human GH (r-hGH) and stores a digital record of adherence that can be shared with healthcare provider. We assessed adherence to r-hGH delivered with Easypod™ according to the approved pediatric indications for r-hGH: growth hormone deficiency (GHD), born small for gestational age (SGA) who failed to show catch-up growth and Turner syndrome (TS). METHODS: ECOS (NCT01555528) was a multicenter (24 countries), 5-year, longitudinal, observational study, which aimed to evaluate country-specific adherence to r-hGH therapy prescribed via the Easypod™ electronic injection device. The primary endpoint was yearly adherence. Secondary endpoints were height velocity, height velocity standard deviation scores (SDS), height, height SDS and IGF-1 concentrations. Clinical and auxological data were obtained from medical records and adherence from Easypod™ logs. RESULTS: This study included 147 Easypod™-naïve Mexican children assessed during 3 years (mean age: 9.96 ± 3.41 years, 56.8% boys, mean height SDS at baseline: - 2.17 ± 0.97): 118 with GHD, 24 SGA and 5 with TS. A total of 105 (71.4%) patients were GH naïve. Overall median adherence was > 90% over the first year of treatment and > 80% at 3 years. Adherence was not different by r-hGH indication or between GH-naïve or experienced patients. At 1-year follow-up, mean change in height SDS was 0.57 ± 0.34, whereas mean height velocity SDS was 2.85 ± 2.51. In all, 84.7% patients had normal IGF-1 concentrations at 1-year follow-up. Adherence was associated with change in height SDS (r = 0.239, p = 0.005) and height velocity SDS (r = 0.194, p = 0.027). CONCLUSION: Adherence rates with the Easypod™ device are high and maintained over time in GHD, SGA and TS Easypod™-naïve Mexican patients. High adherence is associated with better outcomes. Easypod™ assists physicians in monitoring adherence to r-hGH.


Subject(s)
Growth Disorders/drug therapy , Human Growth Hormone/therapeutic use , Medication Adherence/statistics & numerical data , Adolescent , Child , Dwarfism, Pituitary/drug therapy , Dwarfism, Pituitary/epidemiology , Female , Growth Disorders/epidemiology , Hormone Replacement Therapy/methods , Hormone Replacement Therapy/statistics & numerical data , Humans , Infant, Newborn , Infant, Small for Gestational Age/growth & development , Longitudinal Studies , Male , Mexico/epidemiology , Recombinant Proteins/therapeutic use , Turner Syndrome/drug therapy , Turner Syndrome/epidemiology
4.
Int J Biometeorol ; 62(9): 1721-1732, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29948412

ABSTRACT

Pollen allergies have a remarkable clinical impact all over world. Quercus pollen is the main allergen in many parts of world. Due to the health impacts caused by exposure to oak pollen, the objectives of this study are to characterise the aerobiological behaviour of Quercus pollen and to determine its potential sources as well as their transport through the atmosphere of Mexico City and surrounding areas between January 2012 and June 2015. Airborne Quercus pollen monitoring was carried out simultaneously in five zones of Mexico City. The percentage of Quercus pollen of the total pollen collected from the air showed that the highest concentration was recorded in 2014, followed by 2012. The annual seasonal variation indicated that flowering and pollen emission into the atmosphere began between February and March. The maximum concentration of Quercus pollen was reached at Cuajimalpa. In 2012, the amount of pollen grains was distributed in March and April uniformly, whilst in 2014, the largest amount of pollen was concentrated in March. In 2012 and 2014 (years with the highest pollen concentrations), corresponding intraday variations were quite similar, with a low relative maximum in the morning and the highest concentrations in the evening. The largest values were recorded in 2014, and two processes can explain these. In the afternoon, pollen from secondary forest is carried by southwesterly converging winds, increasing the pollen concentration in Cuajimalpa. In the evening, there is an additional pollen contribution from primary forest via transport by NW winds.


Subject(s)
Environmental Monitoring , Pollen , Quercus , Allergens , Atmosphere , Cities , Mexico , Seasons
5.
Photochem Photobiol Sci ; 16(6): 883-889, 2017 Jun 14.
Article in English | MEDLINE | ID: mdl-28379252

ABSTRACT

Several studies suggest that light in the UVA range (320-400 nm) activates signaling pathways that are anti-inflammatory and antioxidative. These effects have been attributed to Nrf2-mediated upregulation of "phase 2" genes such as heme oxygenase-1 (HO-1) that neutralize oxidative stress and metabolize electrophiles. Proteomics analysis previously had shown that small doses of blue light (400-500 nm) increased levels of peroxiredoxin phase 2 proteins in THP-1 monocytes, which led to our hypothesis that blue light activates Nrf2 signaling and thus may serve as an anti-inflammatory agent. THP-1 monocytes were treated with doses of blue light with and without lipopolysaccharide (LPS) inflammatory challenge. Cell lysates were tested for Nrf2 activation and HO-1 production. Treated cells were assessed for viability/mitochondrial activity via trypan blue exclusion and MTT assay, and secretion of two major pro-inflammatory cytokines, interleukin 8 (IL8) and tumor necrosis factor alpha (TNFα) was measured using ELISA. Blue light activated the phase 2 response in cultured THP-1 cells and was protective against LPS-induced cytotoxicity. Light pre-treatment also significantly reduced cytokine secretion in response to 0.1 µg ml-1 LPS, but had no anti-inflammatory effect at high LPS levels. This study is the first to report these effects using a light source that is approved for routine use on dental patients. Cellular responses to these light energies are worth further study and may provide therapeutic interventions for inflammation.


Subject(s)
Inflammation/metabolism , Light , NF-E2-Related Factor 2/metabolism , Signal Transduction/radiation effects , Cells, Cultured , Humans , THP-1 Cells
6.
Br J Anaesth ; 119(4): 750-764, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-29121285

ABSTRACT

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesic drugs. Recent studies have indicated a potential beneficial effect on long-term survival outcomes after cancer surgery but a negative impact on anastomotic leaks. The objective of this study was to objectively assess the implications of the perioperative NSAIDs use on anastomotic leaks and cancer recurrence. METHODS: We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to mid-January 2017. Randomized controlled trials (RCTs) and observational studies in adults undergoing cancer surgery were included for quality assessment. We excluded animal studies, in vitro experiments and case reports. The selected sudies were graded using the Jadad score or Newcastle-Ottawa scale for RCTs and observational retrospective studies, respectively. RESULTS: The systematic review identified 25 trials that explored the impact of NSAIDs on anastomotic leaks and 16 trials that assessed the association between perioperative NSAIDs and cancer recurrence. Meta-analyses were not performed because of high heterogeneity and low quality of the included studies. CONCLUSIONS: The literature is not conclusive on whether the use of NSAIDs is associated with anastomotic leaks after gastrointestinal cancer surgery. Also, the current evidence is equivocal regarding the effects of short-term NSAIDs on cancer recurrence after major cancer surgery. Three RCTs are being conducted to assess the impact of NSAIDs on cancer recurrence. There are no registered RCTs that are testing the hypothesis of whether the perioperative use of NSAIDs increases the rate of anastomotic leaks.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Intraoperative Care/methods , Neoplasms/surgery , Pain, Postoperative/prevention & control , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Humans
7.
J Comput Chem ; 37(26): 2360-73, 2016 10 05.
Article in English | MEDLINE | ID: mdl-27510431

ABSTRACT

Predicting NMR properties is a valuable tool to assist the experimentalists in the characterization of molecular structure. For heavy metals, such as Pt-195, only a few computational protocols are available. In the present contribution, all-electron Gaussian basis sets, suitable to calculate the Pt-195 NMR chemical shift, are presented for Pt and all elements commonly found as Pt-ligands. The new basis sets identified as NMR-DKH were partially contracted as a triple-zeta doubly polarized scheme with all coefficients obtained from a Douglas-Kroll-Hess (DKH) second-order scalar relativistic calculation. The Pt-195 chemical shift was predicted through empirical models fitted to reproduce experimental data for a set of 183 Pt(II) complexes which NMR sign ranges from -1000 to -6000 ppm. Furthermore, the models were validated using a new set of 75 Pt(II) complexes, not included in the descriptive set. The models were constructed using non-relativistic Hamiltonian at density functional theory (DFT-PBEPBE) level with NMR-DKH basis set for all atoms. For the best model, the mean absolute deviation (MAD) and the mean relative deviation (MRD) were 150 ppm and 6%, respectively, for the validation set (75 Pt-complexes) and 168 ppm (MAD) and 5% (MRD) for all 258 Pt(II) complexes. These results were comparable with relativistic DFT calculation, 200 ppm (MAD) and 6% (MRD). © 2016 Wiley Periodicals, Inc.

8.
J Biol Regul Homeost Agents ; 30(2): 323-32, 2016.
Article in English | MEDLINE | ID: mdl-27358117

ABSTRACT

Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non–invasive therapy, in many cases it can represent a first–line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle–skeletal field will grow, not only for standard indications, but also in post–traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses.


Subject(s)
High-Energy Shock Waves/therapeutic use , Musculoskeletal Diseases/therapy , Orthopedics , Traumatology , Biomedical Research , Humans , Regeneration , Tendons/pathology , Tissue Engineering , Wound Healing
9.
Phys Chem Chem Phys ; 18(31): 20895-904, 2016 Aug 21.
Article in English | MEDLINE | ID: mdl-27185388

ABSTRACT

The alkali metal ion affinity of guanine quadruplexes has been studied using dispersion-corrected density functional theory (DFT-D). We have done computational investigations in aqueous solution that mimics artificial supramolecular conditions where guanine bases assemble into stacked quartets as well as biological environments in which telomeric quadruplexes are formed. In both cases, an alkali metal cation is needed to assist self-assembly. Our quantum chemical computations on these supramolecular systems are able to reproduce the experimental order of affinity of the guanine quadruplexes for the cations Li(+), Na(+), K(+), Rb(+), and Cs(+). The strongest binding is computed between the potassium cation and the quadruplex as it occurs in nature. The desolvation and the size of alkali metal cations are thought to be responsible for the order of affinity. Until now, the relative importance of these two factors has remained unclear and debated. By assessing the quantum chemical 'size' of the cation, determining the amount of deformation of the quadruplex needed to accommodate the cation and through the energy decomposition analysis (EDA) of the interaction energy between the cation and the guanines, we reveal that the desolvation and size of the alkali metal cation are both almost equally responsible for the order of affinity.

10.
Phys Chem Chem Phys ; 18(17): 11624-33, 2016 04 28.
Article in English | MEDLINE | ID: mdl-26800159

ABSTRACT

The substituent effect of the amino and nitro groups on the electronic system of benzene has been investigated quantum chemically using quantitative Kohn-Sham molecular orbital theory and a corresponding energy decomposition analysis (EDA). The directionality of electrophilic substitution in aniline can accurately be explained with the amount of contribution of the 2pz orbitals on the unsubstituted carbon atoms to the highest occupied π orbital. For nitrobenzene, the molecular π orbitals cannot explain the regioselectivity of electrophilic substitution as there are two almost degenerate π orbitals with nearly the same 2pz contributions on the unsubstituted carbon atoms. The Voronoi deformation density analysis has been applied to aniline and nitrobenzene to obtain an insight into the charge rearrangements due to the substituent. This analysis method identified the orbitals involved in the C-N bond formation of the π system as the cause for the π charge accumulation at the ortho and para positions in the case of the NH2 group and the largest charge depletion at these same positions for the NO2 substituent. Furthermore, we showed that it is the repulsive interaction between the πHOMO of the phenyl radical and the πHOMO of the NH2 radical that is responsible for pushing up the πHOMO of aniline and therefore activating this π orbital of the phenyl ring towards electrophilic substitution.

12.
Transpl Infect Dis ; 17(2): 308-13, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25726707

ABSTRACT

BACKGROUND: The incidence of bloodstream infection (BSI) varies according to the transplanted organ. Mortality can be as high as 24%, with a significant impact on graft survival. Transplantation is a risk factor for multidrug-resistant (MDR) organisms, but comparison with a non-transplanted population in a single large cohort has not been described. METHODS: This is a prospective nationwide study (16 centers) reporting data on 2364 monomicrobial nosocomial BSIs, comparing 83 episodes in solid organ transplant patients with 2447 BSIs occurring in the general hospital population. RESULTS: The prevalence of groups of infecting organisms (gram-positive, gram-negative, and fungi) was similar between transplant patients and the general population and a similar crude mortality rate was observed (34.9% in transplant vs. 43.3% in non-transplant patients). Staphylococcus aureus was the single most frequently isolated organism in both groups, and Acinetobacter species was more frequently isolated in the general population. Regarding MDR organisms, Klebsiella species, and Enterobacter species resistant to cefepime, as well as Acinetobacter species resistant to meropenem, were significantly more frequent in transplant patients. CONCLUSION: Antimicrobial resistance is higher, particularly among gram-negative bacteria in the transplant population, although the overall mortality rate between transplant and non-transplant patients with nosocomial BSI is similar.


Subject(s)
Bacteremia/epidemiology , Candidemia/epidemiology , Cross Infection/epidemiology , Transplant Recipients/statistics & numerical data , Acinetobacter Infections/epidemiology , Acinetobacter Infections/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/microbiology , Brazil/epidemiology , Candidemia/microbiology , Child , Child, Preschool , Cross Infection/microbiology , Drug Resistance, Bacterial , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Female , Fungemia/epidemiology , Fungemia/microbiology , Humans , Infant , Infant, Newborn , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Male , Middle Aged , Prospective Studies , Pseudomonas Infections/epidemiology , Pseudomonas Infections/microbiology , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Young Adult
13.
Rev Med Chil ; 143(5): 673-6, 2015 May.
Article in Spanish | MEDLINE | ID: mdl-26203581

ABSTRACT

Anatomic variations of the hepatic artery, which occur in 30 to 50% of patients, are a very important factor to be considered for Whipple procedure. The most common variations are those coming from the superior mesenteric artery, left gastric artery and the aorta. We report a 58-year-old woman with a story of one month of epigastric pain, jaundice and progressive itching. Magnetic resonance imaging showed a mass in the head of the pancreas. During pancreatoduodenectomy a left hepatic artery (LHA) emerging from the gastroduodenal artery and an accessory LHA emerging from the left gastric artery, were observed. The rest of the surgery was performed with no incidents. The patient had an uneventful postoperative evolution.


Subject(s)
Hepatic Artery/abnormalities , Pancreaticoduodenectomy/methods , Anatomic Variation , Female , Hepatic Artery/surgery , Humans , Medical Illustration , Middle Aged
14.
Med Intensiva ; 39(7): 433-41, 2015 Oct.
Article in English, Spanish | MEDLINE | ID: mdl-25444059

ABSTRACT

OBJECTIVE: To study the results of a non-controlled cardiac death (Maastricht type II) donor program in a city of 200,000 inhabitants. The study was initially focused on lung donation and was extended to kidney donation after 9 months. DESIGN: A prospective observational study was conducted between October 2012 and December 2013. SETTING: The Intensive Care Unit of Marqués de Valdecilla University Hospital in Santander (Spain), and surrounding areas. POPULATIONS: Patients (< 55 years) who died of out-of-hospital cardiac arrest. INTERVENTIONS: All out-of-hospital cardiac arrests were treated with mechanical cardiac compression (LUCAS II). The diagnosis of death and organ preservation were performed in the ICU. RESULTS: A total of 14 calls were received, of which three were discarded. Of the 11 potential donors, 7 were effective donors with a median age of 39.5 years (range: 32-48). A total of 5 single lung transplants and four kidney transplants were performed. In addition, corneas and tissues were harvested. The non-valid donors were rejected mainly due to technical problems. There were no donation refusals on the part of the patient relatives. The lung transplant patient survival rate was 100% after one month and 80% after one year. One month after transplantation, the kidney recipients had a serum creatinine concentration of<2mg/dl. The interval from cardiac arrest to renal preservation was 80minutes (range: 71-89), and the interval from cardiac arrest to lung preservation was 84minutes (range: 77-94). CONCLUSIONS: A Maastricht type II donation program in a small city is viable for both abdominal and thoracic organs. The program was initially very cautious, but its potential is easily improvable by increasing donor and by equipping mobile ICU ambulances with mechanical cardiac compression systems. Full management of the donor in the ICU, avoiding the emergency department or operating rooms, reduces the warm ischemia time, thereby improving transplant outcomes.


Subject(s)
Out-of-Hospital Cardiac Arrest/mortality , Tissue Donors , Tissue and Organ Procurement/organization & administration , Adult , Ambulances , Cardiopulmonary Resuscitation/instrumentation , Cities , Female , Graft Survival , Hospitals, University , Humans , Kidney Transplantation , Lung Transplantation , Male , Middle Aged , Organ Preservation/methods , Out-of-Hospital Cardiac Arrest/therapy , Program Evaluation , Prospective Studies , Respiration, Artificial , Spain , Tissue and Organ Harvesting/methods , Tissue and Organ Procurement/methods , Tissue and Organ Procurement/standards , Urban Health Services , Warm Ischemia , Young Adult
15.
Rev Chil Pediatr ; 85(2): 148-56, 2014 Apr.
Article in Spanish | MEDLINE | ID: mdl-25697202

ABSTRACT

Intestinal failure is defined as the reduction of a functional gut mass below the minimal necessary for adequate digestion and absorption of nutrients and fluids. Intestinal failure is the final result of a number of different causes, being short bowel syndrome the most recognized. Its prevalence is low, but the impact in quality of life among patients and their families is critical. Furthermore, is associated with high economic costs, both for the patient and the health provider. Its main feature is the need for long-term parenteral nutritional support with high morbidity and mortality associated complications, such as line-derived bloodstream infections and liver disease. The management of these patients should be performed by a multidisciplinary team, and be aimed at promoting adaptation and recovery of bowel function to achieve intestinal autonomy.


Subject(s)
Intestinal Diseases/therapy , Quality of Life , Short Bowel Syndrome/therapy , Adaptation, Physiological/physiology , Child , Humans , Intestinal Absorption , Intestinal Diseases/etiology , Intestinal Diseases/physiopathology , Parenteral Nutrition/methods , Patient Care Team/organization & administration , Short Bowel Syndrome/physiopathology
16.
Br J Cancer ; 109(4): 926-33, 2013 Aug 20.
Article in English | MEDLINE | ID: mdl-23907428

ABSTRACT

BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fibroblasts/pathology , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Albumins/administration & dosage , Albumins/pharmacology , Animals , CA-19-9 Antigen/blood , Collagen/drug effects , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Disease Models, Animal , Elasticity Imaging Techniques , Endosonography , Female , Fibroblasts/drug effects , Humans , Male , Mice , Middle Aged , Neoadjuvant Therapy , Paclitaxel/administration & dosage , Paclitaxel/pharmacology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Positron-Emission Tomography , Gemcitabine
17.
Article in English | MEDLINE | ID: mdl-23416890

ABSTRACT

Predation is known to impact growth and reproduction, and the physiological state of the prey, including its susceptibility to oxidative stress. In this study, we investigated how prolonged exposure to predators modulates tissue specific antioxidant defense and oxidative damage in the short-lived epibenthic scallop Argopecten ventricosus (2years maximum lifespan). Scallops that were experimentally exposed to predators had not only lower antioxidant capacities (superoxide dismutase and catalase), but also lower oxidative damage (protein carbonyls and TBARS=thiobarbituric acid reactive substances including lipid peroxides) in gills and mantle compared to individuals not exposed to predators. In contrast, oxidative damage in the swimming muscle was higher in predator-exposed scallops. When predator-exposed scallops were on the verge of spawning, levels of oxidative damage increased in gills and mantle in spite of a parallel increase in antioxidant defense in both tissues. Levels of oxidative damage increased also in the swimming muscle whereas muscle antioxidant capacities decreased. Interestingly, post-spawned scallops restored antioxidant capacities and oxidative damage to immature levels, suggesting they can recover from spawning-related oxidative stress. Our results show that predator exposure and gametogenesis modulate oxidative damage in a tissue specific manner and that high antioxidant capacities do not necessarily coincide with low oxidative damage.


Subject(s)
Oxidation-Reduction , Oxidative Stress , Pectinidae/physiology , Reproduction/physiology , Animals , Antioxidants/metabolism , Catalase/metabolism , Gills/metabolism , Gills/physiology , Lipid Peroxidation/physiology , Predatory Behavior/physiology , Superoxide Dismutase/metabolism
18.
Clin Ter ; 174(4): 331-335, 2023.
Article in English | MEDLINE | ID: mdl-37378502

ABSTRACT

Background: The aim of our study was to assess how total intra-venous anaesthesia (TIVA) achieved by propofol and remifentanil continuous infusion could ensure proper success of the endobronchial laser therapy, in optimal conditions for the endoscopist, determining at the same time an adequate hypnosis and a good analgesia. Methods: We studied 50 patients (28M - 22F), ASA class I-IV, mean age 42 ± 32.5 years , subjected to laser endoscopy to repair tracheal stenosis. TIVA was performed in all patients, and spontaneous breathing was maintained. Results: 10.2% of patients experienced episodes of coughing during induction. The depth of the anaesthesia plan, monitored by BIS, was 55 ± 5. The awakening was fast in all patients, with an Aldrete score of 7.71 ± 1.14 at 1 minute and 9.31 ± 1.12 at 10 minutes. Conclusion: The results of this study allow us to state that the continuous infusion of propofol and remifentanil proved to be the gold standard in patients ASA I-II-III undergoing endobronchial laser therapy. The use of TIVA has also allowed to perform endoscopic intervention on patients who suffered from a significant decrease of both cardiac and respiratory functions.


Subject(s)
Laser Therapy , Propofol , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Remifentanil , Propofol/pharmacology , Anesthetics, Intravenous/pharmacology , Anesthesia, Intravenous , Endoscopy , Lasers
19.
Neurologia (Engl Ed) ; 38(6): 379-386, 2023.
Article in English | MEDLINE | ID: mdl-37120112

ABSTRACT

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.


Subject(s)
Cerebellar Ataxia , Spastic Paraplegia, Hereditary , Male , Humans , Female , Middle Aged , Spastic Paraplegia, Hereditary/epidemiology , Spastic Paraplegia, Hereditary/genetics , Cross-Sectional Studies , Retrospective Studies , Spain/epidemiology
20.
Clin Exp Immunol ; 168(1): 142-52, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22385249

ABSTRACT

We characterized the underlying mechanisms by which glutathione (GSH)-enhanced natural killer (NK) cells inhibit the growth of Mycobacterium tuberculosis (M. tb) inside human monocytes. We observed that in healthy individuals, treatment of NK cells with N-acetyl cysteine (NAC), a GSH prodrug in conjunction with cytokines such as interleukin (IL)-2 + IL-12, resulted in enhanced expression of NK cytotoxic ligands (FasL and CD40L) with concomitant stasis in the intracellular growth of M. tb. Neutralization of FasL and CD40L in IL-2 + IL-12 + NAC-treated NK cells resulted in abrogation in the growth inhibition of M. tb inside monocytes. Importantly, we observed that the levels of GSH are decreased significantly in NK cells derived from individuals with HIV infection compared to healthy subjects, and this decrease correlated with a several-fold increase in the growth of M. tb inside monocytes. This study describes a novel innate defence mechanism adopted by NK cells to control M. tb infection.


Subject(s)
Acetylcysteine/pharmacology , Killer Cells, Natural/immunology , Mycobacterium tuberculosis/immunology , CD40 Ligand/antagonists & inhibitors , CD40 Ligand/biosynthesis , Fas Ligand Protein/biosynthesis , Female , Glutathione/pharmacology , HIV Infections/immunology , Humans , Immunity, Innate , Interleukin-12/metabolism , Interleukin-2/metabolism , Killer Cells, Natural/drug effects , Killer Cells, Natural/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/microbiology , Lymphocyte Activation , Male , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/pathogenicity , NK Cell Lectin-Like Receptor Subfamily K/analysis , Tuberculosis/immunology
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