Publications by authors named "Caroline Baldo"

24 Publications

  • Page 1 of 1

Novel Pathway of Adenosine Generation in the Lungs from NAD: Relevance to Allergic Airway Disease.

Molecules 2020 Oct 27;25(21). Epub 2020 Oct 27.

Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.

Adenosine and uric acid (UA) play a pivotal role in lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). In the present experiments, we measured adenosine synthesis from nicotinamide adenine dinucleotide (NAD) in membranes prepared from wild type (WT) and CD38 knockout (CD38KO) mouse lungs, from cultured airway smooth muscle and epithelial cells, and in bronchoalveolar lavage fluid after airway challenge with epidemiologically relevant allergens. Adenosine was determined using an enzymatically coupled assay that produces ATP and is detected by luminescence. Uric acid was determined by ELISA. Exposure of cultured airway epithelial cells to extract caused significant nucleotide (NAD and ATP) release in the culture media. The addition of NAD to membranes prepared from WT mice resulted in faster generation of adenosine compared to membranes from CD38KO mice. Formation of adenosine from NAD affected UA and ATP concentrations, its main downstream molecules. Furthermore, NAD and adenosine concentrations in the bronchoalveolar lavage fluid decreased significantly following airway challenge with house-dust mite extract in WT but not in CD38KO mice. Thus, NAD is a significant source of adenosine and UA in the airways in mouse models of allergic airway disease, and the capacity for their generation from NAD is augmented by CD38, a major NADase with high affinity for NAD. This novel non-canonical NAD-adenosine-UA pathway that is triggered by allergens has not been previously described in the airways.
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http://dx.doi.org/10.3390/molecules25214966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663290PMC
October 2020

Owner evaluation of quality of life and mobility in osteoarthritic cats treated with amantadine or placebo.

J Feline Med Surg 2021 Jun 28;23(6):568-574. Epub 2020 Oct 28.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA.

Objectives: The aim of the study was to determine if amantadine improves owner-identified mobility impairment and quality of life associated with osteoarthritis in cats.

Methods: Using a blinded, placebo-controlled, randomized, crossover design, 13 healthy client-owned cats with clinical and radiographic evidence of osteoarthritis and owner-identified mobility impairment were studied. Cats received 5 mg/kg amantadine or placebo q24h PO for 3 weeks each with no washout period in between. Locomotor activity was continuously assessed with a collar-mounted activity monitor system, and owners chose and rated two mobility-impaired activities using a client-specific outcome measures (CSOM) questionnaire on a weekly basis. Locomotor activity on the third treatment week was analyzed with two-tailed paired -tests. The CSOM scores were analyzed using a mixed-effect model and the Bonferroni post-hoc test. Owner-perceived changes in quality of life were compared between treatments using the χ test. Statistical significance was set at 0.05.

Results: Mean ± SD activity counts during the third week of each treatment were significantly lower with amantadine (240,537 ± 53,880) compared with placebo (326,032 ± 91,759). CSOM scores assigned by the owners were significantly better with amantadine on the second (3 ± 1) and third (3 ± 1) weeks compared with placebo (5 ± 2 and 5 ± 1, respectively). A significantly greater proportion of owners reported improvement in quality of life with amantadine compared with placebo.

Conclusions And Relevance: Amantadine significantly decreased activity, but improved owner-identified impaired mobility and owner-perceived quality of life in cats with osteoarthritis. Amantadine appears to be an option for the symptomatic treatment of osteoarthritis in cats.
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http://dx.doi.org/10.1177/1098612X20967639DOI Listing
June 2021

Anesthetic risk during subsequent anesthetic events in brachycephalic dogs that have undergone corrective airway surgery: 45 cases (2007-2019).

J Am Vet Med Assoc 2020 Oct;257(7):744-749

Objective: To determine whether previous corrective upper airway surgery in brachycephalic dogs would decrease perianesthetic complications in subsequent anesthetic events.

Animals: 45 client-owned dogs.

Procedures: Brachycephalic dogs undergoing any combination of staphylectomy, nasal alaplasty, or laryngeal sacculectomy that were anesthetized at a later date for additional surgical procedures or imaging from August 2, 2007, to February 8, 2019, had their medical records reviewed during both anesthetic events for signalment, American Society of Anesthesiologists status, perianesthetic drug administration, anesthetic duration, presence and total time of positive-pressure ventilation, procedure invasiveness, and perianesthetic complications such as bradycardia, hypothermia, hypotension, cardiac arrhythmias, hypertension, vomiting or regurgitation, dysphoria, respiratory distress, hypoxemia, reintubation, and prolonged periods of recovery.

Results: The odds of having complications during the postanesthetic period following subsequent anesthetic events were decreased by 79% in dogs having previous surgical intervention to correct clinical signs of brachycephalic airway syndrome. Intra-anesthetic bradycardia increased the odds of developing a postanesthetic complication by 4.56 times. Every 15-minute increase in anesthetic duration increased the odds of having a postanesthetic complication by 12% and having an intra-anesthetic complication by 11%.

Conclusions And Clinical Relevance: Previous corrective upper airway surgery decreased odds of postanesthetic complications in brachycephalic dogs that underwent subsequent anesthetic events. Findings in this study indicated that corrective upper airway surgery for brachycephalic dogs may reduce postanesthetic complications following subsequent anesthetic events, which may reduce perianesthetic morbidity in patients undergoing multiple surgical or diagnostic imaging procedures.
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http://dx.doi.org/10.2460/javma.257.7.744DOI Listing
October 2020

Pharmacokinetics and clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia.

J Vet Pharmacol Ther 2020 Jul 12;43(4):369-376. Epub 2020 Mar 12.

Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, Minneapolis, MN, USA.

This study determined the pharmacokinetics and compared the clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. Six healthy horses aged 8.5 ± 3 years and weighing 462 ± 50 kg were anesthetized with isoflurane for 2 hr under standard conditions on two occasions one-week apart. In recovery, horses received 200 μg/kg xylazine or 0.875 μg/kg dexmedetomidine intravenously and were allowed to recover without assistance. These doses were selected because they have been used for postanesthetic sedation in clinical and research studies. Serial venous blood samples were collected for quantification of xylazine and dexmedetomidine, and the pharmacokinetic parameters were calculated. Two individuals blinded to treatment identity evaluated recovery quality with a visual analog scale. Times to stand were recorded. Results (mean ± SD) were compared using paired t tests or Wilcoxon signed-ranked test with p < .05 considered significant. Elimination half-lives (62.7 ± 21.8 and 30.1 ± 8 min for xylazine and dexmedetomidine, respectively) and steady-state volumes of distribution (215 ± 123 and 744 ± 403 ml/kg) were significantly different between xylazine and dexmedetomidine, whereas clearances (21.1 ± 17.3 and 48.6 ± 28.1 ml/minute/kg), times to stand (47 ± 24 and 53 ± 12 min) and recovery quality (51 ± 24 and 61 ± 22 mm VAS) were not significantly different. When used for postanesthetic sedation following isoflurane anesthesia in healthy horses, dexmedetomidine displays faster plasma kinetics but is not associated with faster recoveries compared to xylazine.
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http://dx.doi.org/10.1111/jvp.12855DOI Listing
July 2020

Rabbit supraglottic airway device (V-GEL) for successful airway control in a hedgehog (Atelerix albiventris).

Vet Anaesth Analg 2020 01 29;47(1):141-143. Epub 2019 Aug 29.

Veterinary Medical Center, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.

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http://dx.doi.org/10.1016/j.vaa.2019.07.003DOI Listing
January 2020

ECG of the Month.

J Am Vet Med Assoc 2018 Jul;253(1):46-48

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http://dx.doi.org/10.2460/javma.253.1.46DOI Listing
July 2018

Why Methylene Blue Have to Be Always Present in the Stocking of Emergency Antidotes.

Curr Drug Targets 2018 ;19(13):1550-1559

Department of Surgery and Anatomy, Ribeirao Preto School of Medicine, University of Sao Paulo, SP, Brazil.

Evidence-based review of the existing literature ultimately recommends stocking of Methylene Blue (MB) as an emergency antidote in the United States. The same is reported around the world in Japan, Greece, Italy and Canada. The observation that MB is always present as the main antidote required in emergency and critical care units calls for a revisit on its effects on the NO/cGMP system to reemphasize its multisystem actions. Therefore, the present review aimed to display the role of MB in emergency units, concerning: 1) Polytrauma and circulatory shock; 2) Neuroprotection, 3) Anaphylaxis and, 4) Overdose and poisoning.
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http://dx.doi.org/10.2174/1389450119666180403100410DOI Listing
October 2019

Transversus abdominis plane block in ponies: a preliminary anatomical study.

Vet Anaesth Analg 2018 May 7;45(3):392-396. Epub 2018 Feb 7.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.

Objective: To describe a single-site transversus abdominis plane (TAP) block technique in horses.

Study Design: Prospective, descriptive, experimental anatomical study.

Animals: Four adult pony cadavers.

Methods: Freshly euthanized ponies were positioned in dorsal recumbency. A 6-13 MHz linear ultrasonic probe was used to scan the abdominal wall bilaterally midway between the last rib and iliac crest in search of the TAP location. By modifying the technique to accommodate the equine anatomy, the TAP was successfully visualized with the transducer positioned in a transverse plane with its side indicator over the intercept of two lines, one connecting the most cranial aspect of the iliac crest and the most caudal extent of the last rib and another originating just caudal to the umbilicus and extending laterally. Each hemiabdomen was injected with 0.5 mL kg of a 1:1 solution of 1% methylene blue and 0.5% bupivacaine via a 21 gauge 10 cm stimulating needle inserted ventral-dorsally and in plane with the ultrasound beam. Approximately 3 hours after injection, the abdomen was dissected and nerves stained over 1 cm in length were identified.

Results: Staining was evident from the fourteenth thoracic (T14) to the third lumbar (L3) nerves. The ventral branches of the fifteenth to the eighteenth thoracic nerves (T15-T18) and first and second lumbar nerves (L1 and L2) were stained in three, six, eight, eight, eight and seven of eight injections, respectively.

Conclusions And Clinical Relevance: Nerves T16-L2 had over 75% success rate in staining, suggesting that this technique would block transmission from T16 to L2, assuming that staining indicates potential nerve block. Dorsal spread occurred in three of eight hemiabdomens. Further studies developing techniques for the cranial abdomen and adjusting volume and concentration of injectate are warranted.
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http://dx.doi.org/10.1016/j.vaa.2018.01.009DOI Listing
May 2018

Guanylate cyclase inhibition by methylene blue in circulatory shock caused by acute necrotizing pancreatitis: a word of caution based on a porcine model.

Rev Col Bras Cir 2013 Nov-Dec;40(6):480-9

Objective: To study the therapeutic application of guanylate cyclase inhibition by methylene blue in an experimental model of acute pancreatitis in pigs.

Methods: acute necrotizing pancreatitis was induced in anesthetized pigs by the retrograde infusion of 1 ml/kg of 5% sodium taurocholate and 8 U/kg enterokinase in the pancreatic duct. Three groups were studied (n = 5): control (C), pancreatitis (AP), and MB bolus followed by pancreatitis (MB+P). The data included serum and abdominal fluid enzymes, hemodynamic variables, arterial hemogasometry, abdominal fluid volume, inflammatory markers, plasma nitrite/nitrate (NOx), plasma myeloperoxidase (MPO) and plasma malondialdehyde (MDA). One- and two-way analysis of variance (ANOVA) was performed, followed by the Bonferroni test (p < 0.05).

Results: amylase and lipase were three and 10-fold higher in the AP group. Myeloperoxidase activity was 50% higher in the AP group. The hemodynamic data indicated early hypovolemic shock followed by cardiogenic shock. Severe fluid translocation to the peritoneal cavity was observed. Plasma NOx remained unchanged. The MB+P group had a five-fold increase in MDA compared with the C group.

Conclusion: preemptive application of MB in pigs with AP demonstrated no significant effects on hemodynamic and inflammatory variables. The use of MB is inadequate in cases of exponential NO release, and extreme caution must be exercised, given the increase in lipid peroxidation based on the malondialdehyde dosage.
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http://dx.doi.org/10.1590/s0100-69912013000600011DOI Listing
April 2015

Effects of anesthetic drugs on canine splenic volume determined via computed tomography.

Am J Vet Res 2012 Nov;73(11):1715-9

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Objective: To evaluate effects of commonly used anesthetics administered as single bolus injections on splenic volume.

Animals: 10 adult Beagles.

Procedures: A randomized crossover study was conducted. Computed tomography was performed on dogs to determine baseline splenic volume and changes after IV injection of assigned drug treatments. Dogs were allowed to acclimate for 10 minutes in a plastic crate before acquisition of abdominal CT images. Treatments were administered at 7-day intervals and consisted of IV administration of saline (0.9% NaCl) solution (5 mL), acepromazine maleate (0.03 mg/kg), hydromorphone (0.1 mg/kg), and dexmedetomidine (0.005 mg/kg) to all 10 dogs; thiopental (8 mg/kg) to 5 of the dogs; and propofol (5 mg/kg) to the other 5 dogs. Splenic volume was calculated from the CT images with image processing software. A repeated-measures ANOVA was performed, followed by a Bonferroni post hoc test.

Results: No significant difference in splenic volume was detected between the acepromazine, propofol, and thiopental treatments, but splenic volume was greater with these drugs than with saline solution, hydromorphone, and dexmedetomidine. Splenic volume was less with hydromorphone, compared with dexmedetomidine, but splenic volume with hydromorphone and dexmedetomidine did not differ significantly from that with saline solution.

Conclusions And Clinical Relevance: Administration of acepromazine, thiopental, and propofol resulted in splenomegaly. Dexmedetomidine did not alter splenic volume. Hydromorphone slightly decreased splenic volume. Propofol should not be used when splenomegaly is not desirable, whereas hydromorphone and dexmedetomidine may be used when it is best to avoid splenic enlargement.
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http://dx.doi.org/10.2460/ajvr.73.11.1715DOI Listing
November 2012

Conservation of avian germplasm by xenogeneic transplantation of spermatogonia from sexually mature donors.

Stem Cells Dev 2013 Mar 28;22(5):735-49. Epub 2012 Nov 28.

Departamento de Reprodução Animal, Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, São Paulo, Brazil.

Approximately 12.5% of all 9,920 extant bird species in the world are threatened with extinction, and yet conservation efforts through natural breeding of captive species continue to encounter difficulties. However, sperm cryopreservation and artificial insemination offer potential benefits over natural breeding, but their applicability is still limited in nondomestic species. In this study, we aimed to exploit the potential of germ cell xenotransplantation as an alternative tool for preserving germplasm of endangered birds. The study was designed to investigate whether transfer of either spermatogonia-enriched cell fraction (SEF) or crude testicular cell fraction (CTF) from adult Japanese quails (as a model for wild species) would result in recolonization of gamma-irradiated gonads of adult recipient chickens. One month after transplantation, 75% of recipients injected with SEF and 25% of recipients injected with CTF resumed spermatogenesis. However, it took more than 3 months for 33% of the negative controls to resume marginal production of sperm. Some SEF recipients produced more spermatozoa bearing head morphology compared with donor controls. DNA analysis using quail-specific primers did not detect donor's DNA in these recipients' semen. However, 6 months after xenotransplantation, presence of quail germ cells was demonstrated by polymerase chain reaction and by immunohistochemistry in 1 rooster injected with SEF. These findings indicate that spermatogonia from adult quails were capable of colonizing immunocompetent testis of adult chickens but failed to produce sufficient sperm. Despite this limitation, the present approach represents a potential conservation tool that may be used to rescue germ cells of endangered adult male birds.
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http://dx.doi.org/10.1089/scd.2012.0497DOI Listing
March 2013

[Emergency care for victims of violence and accidents: differences in the epidemiological profile between the public and private health services. VIVA--Campinas, São Paulo, Brazil, 2009].

Cien Saude Colet 2012 Sep;17(9):2279-90

Departamento de Saúde Coletiva, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Rua Tessália Vieira de Camargo 126, CCAS/Depto de Saúde Coletiva, Cid. Universitária Zeferino Vaz, 13083-887 Campinas SP.

The scope of this study is to analyze the differences in the profile of emergency care for external causes between public and private emergency departments. With data come from VIVA-Campinas 2009, the association between the nature of healthcare and the characteristics of the victims was verified using the chi-square test. Using Poisson regression, proportion ratios of care in the public and private network were estimated. In the sample of 1094 victims, 67.8% were treated by public health. Traffic accidents, animal-related accidents, and assaults were 2 times higher in public units, whereas collisions with objects and sprains were 75% and 2.7 times higher in private units. Cranium-encephalic trauma/polytrauma and cuts/lacerations were 3.8 times and 61% more frequent in public care, while victims with no injuries, with dislocations/sprains or fractures being predominant in private care. Head and multiple organ injuries, road accident and work-related injuries, the use of public transport or mobile emergency care services/ambulances were predominant in public care. Revealing significant differences in care in public and private care can contribute to the organization of healthcare.
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http://dx.doi.org/10.1590/s1413-81232012000900010DOI Listing
September 2012

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats.

Arq Bras Endocrinol Metabol 2010 Aug;54(6):530-9

Departamento de Cirurgia e Anatomia, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Objectives: To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters.

Methods: Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats.

Results: MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups.

Conclusions: NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress.
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http://dx.doi.org/10.1590/s0004-27302010000600004DOI Listing
August 2010

Vascular relaxation of canine visceral arteries after ischemia by means of supraceliac aortic cross-clamping followed by reperfusion.

Scand J Trauma Resusc Emerg Med 2010 Jul 19;18:41. Epub 2010 Jul 19.

Department of Surgery and Anatomy, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.

Background: The supraceliac aortic cross-clamping can be an option to save patients with hipovolemic shock due to abdominal trauma. However, this maneuver is associated with ischemia/reperfusion (I/R) injury strongly related to oxidative stress and reduction of nitric oxide bioavailability. Moreover, several studies demonstrated impairment in relaxation after I/R, but the time course of I/R necessary to induce vascular dysfunction is still controversial. We investigated whether 60 minutes of ischemia followed by 30 minutes of reperfusion do not change the relaxation of visceral arteries nor the plasma and renal levels of malondialdehyde (MDA) and nitrite plus nitrate (NOx).

Methods: Male mongrel dogs (n = 27) were randomly allocated in one of the three groups: sham (no clamping, n = 9), ischemia (supraceliac aortic cross-clamping for 60 minutes, n = 9), and I/R (60 minutes of ischemia followed by reperfusion for 30 minutes, n = 9). Relaxation of visceral arteries (celiac trunk, renal and superior mesenteric arteries) was studied in organ chambers. MDA and NOx concentrations were determined using a commercially available kit and an ozone-based chemiluminescence assay, respectively.

Results: Both acetylcholine and calcium ionophore caused relaxation in endothelium-intact rings and no statistical differences were observed among the three groups. Sodium nitroprusside promoted relaxation in endothelium-denuded rings, and there were no inter-group statistical differences. Both plasma and renal concentrations of MDA and NOx showed no significant difference among the groups.

Conclusion: Supraceliac aortic cross-clamping for 60 minutes alone and followed by 30 minutes of reperfusion did not impair relaxation of canine visceral arteries nor evoke biochemical alterations in plasma or renal tissue.
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http://dx.doi.org/10.1186/1757-7241-18-41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913934PMC
July 2010

Exhaled breath condensate collection for nitrite dosage: a safe and low cost adaptation.

Acta Cir Bras 2010 Apr;25(2):206-13

Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine, USP, Ribeirão Preto - São Paulo, Brazil.

Purpose: Standardization of a simple and low cost technique of exhaled breath condensate (EBC) collection to measure nitrite.

Methods: Two devices were mounted in polystyrene boxes filled either with crushed ice/salt crystals or dry ice/crushed ice. Blood samples were stored at -70 degrees C for posterior nitrite dosages by chemiluminescence and the Griess reaction.

Results: a) The use of crushed ice/dry ice or salt revealed sufficient EBC room air collection, but was not efficient for patients under ventilation support; b) the method using crushed ice/salt collected greater EBC volumes, but the nitrite concentrations were not proportional to the volume collected; c) The EBC nitrite values were higher in the surgical group using both methods; d) In the surgical group the nasal clip use diminished the EBC nitrite concentrations in both methods.

Conclusions: The exhaled breath condensate (EBC) methodology collection was efficient on room air breathing. Either cooling methods provided successful EBC collections showing that it is possible to diminish costs, and, amongst the two used methods, the one using crushed ice/salt crystals revealed better efficiency compared to the dry ice method.
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http://dx.doi.org/10.1590/s0102-86502010000200015DOI Listing
April 2010

Diabetes and vascular disease: basic concepts of nitric oxide physiology, endothelial dysfunction, oxidative stress and therapeutic possibilities.

Curr Vasc Pharmacol 2010 Jul;8(4):526-44

Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

The vascular manifestations associated with diabetes mellitus (DM) result from the dysfunction of several vascular physiology components mainly involving the endothelium, vascular smooth muscle and platelets. It is also known that hyperglycemia-induced oxidative stress plays a role in the development of this dysfunction. This review considers the basic physiology of the endothelium, especially related to the synthesis and function of nitric oxide. We also discuss the pathophysiology of vascular disease associated with DM. This includes the role of hyperglycemia in the induction of oxidative stress and the role of advanced glycation end-products. We also consider therapeutic strategies.
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http://dx.doi.org/10.2174/157016110791330834DOI Listing
July 2010

Glycol methacrylate-embedding medium to study morphological alterations of saphenous vein under brief and crescent pressurizations.

Acta Cir Bras 2008 ;23 Suppl 1:77-82; discussion 82

Department of Pathology, Ribeirão Preto Faculty of Medicine, University of São Paulo, SP, Brazil.

Purpose: This study sought to evaluate the efficiency of glycol methacrylate-embedding medium to detect morphological alterations of human saphenous vein submitted to brief and crescent pressurizations.

Methods: Saphenous veins of 20 CABG patients were randomly distributed into four experimental groups (control, 100, 200 and 300 mmHg pressures during 15 seconds). To quantify the percentage of endothelium spread over vein surface a microscope magnification of 100x was used for measurements. Morphometric analysis was performed using videomicroscopy with the Leica Qwin software in conjunction with a Leica microscope, videocamera, and an on-line computer.

Results: A slight tendency of quantitative increase was observed in all parameters including percentage of endothelium spread over vein surface and thickness of saphenous vein walls (intima and media layers).

Conclusions: The glycol methacrylate-embedding allowed sections with adequate resolution of structural details and revealed to be an extremely useful method to study pressurized human saphenous veins.
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http://dx.doi.org/10.1590/s0102-86502008000700014DOI Listing
June 2009

Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction.

Acta Cir Bras 2008 ;23 Suppl 1:66-71; discussion 71

Division of Digestive Surgery, Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine, University of São Paulo, SP, Brazil.

Purpose: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature.

Methods: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and analysis. Mitochondrial oxygen consumption was determined by stage 3 velocity and stage 4 velocity. The respiratory control ratio (RCR) was obtained by the ratio of stage 3 to stage 4 velocity. Statistical analysis was performed by the Mann-Whitney test, with the level of significance set at 5% (p<0.05).

Results: Statistical analysis revealed a significant drop in oxygen consumption during stage 3 mitochondrial respiration in group IC compared with SO, whereas the values obtained during stage 4 were basically identical for the two groups. Likewise, RCR values exhibited a significant reduction.

Conclusion: The cellular respiration of the "jaundiced heart" is depressed. This was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, supporting the idea of a latent cardiac impairment responsible for the hemodynamic decompensation occurring during cholestasis.
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http://dx.doi.org/10.1590/s0102-86502008000700012DOI Listing
June 2009

Methylene blue improves hemodynamic shock but increases lipoperoxidation in severe acute pancreatitis pig model.

Acta Cir Bras 2008 ;23 Suppl 1:8-16; discussion 16

Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine, University of São Paulo, SP, Brazil.

Purpose: Study hemodynamic pattern and lipoperoxidation during methylene blue (MB) treatment on taurocholate - enterokinase induced acute pancreatitis (AP).

Methods: Thirty pigs were equally divided in control group; MB group; AP group; MB previous AP group; and MB after 90 min of induced AP group. MB was given iv in a bolus dose (2 mg.kg-1) followed by maintenance dose (2 mg.kg-1.h-1). Hemodynamic parameters were recorded continuously during 180 min by Swan-Ganz catheter. Blood samples were taken every 60 min to determine arterial and venous nitrate, malondialdehyde (MDA) and amylase. Pancreatic tissue was removed for histopathologic study.

Results: In AP group MBP and CO decreased over time 33% (p<0.05) and 52% (p<0.05), respectively. In MB previous induced-AP group, there was 70 minutes delay (p<0.05) to decrease MBP and CO. In MB group arterial and venous nitrite decreased (p<0.05) over time. MB infusion increased (p>0.05) serum MDA when associated to AP. After induced AP, MB did not reverse MBP and CO decrease. There was no difference in serum amylase and necro-hemorrhagic findings with MB treatment.

Conclusions: In this taurocholate-induced AP model MB treatment delayed hemodynamic shock and decreases serum nitrate levels but increases serum MDA levels. No volemic replacement was done and it may have been a mitigated factor to a poor tissue perfusion and impairment microcirculation. Further investigations are needed to elucidate MB treatment role during AP treatment.
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http://dx.doi.org/10.1590/s0102-86502008000700003DOI Listing
June 2009

Liver histological, portal flow and plasmatic nitric oxide alterations caused by biliary obstruction and drainage in rats.

Acta Cir Bras 2008 ;23 Suppl 1:2-7; discussion 7

Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine, University of São Paulo, SP, Brazil.

Purpose: To evaluate liver alterations caused by biliary obstruction and drainage.

Methods: Thirty-nine male Wistar rats were randomly distributed in 4 groups: BO (n=18) bile duct ligation for 20 days, with a periodic evaluation of liver histological alterations, Doppler echography portal flow and measurements of NO and malondialdehyde (MDA); BO/DB (n=13) bile duct occlusion for 20 days followed by biliary drainage by choledochoduodenal anastomosis, 5 days follow-up, same BO group parameters evaluations; group CED (n=4) sham operation and portal flow evaluation trough 20 days; CHB (n=4) sham operation, with hepatic biopsy on 25th day and followed-up trough 25 days, by the same parameters of group BO, with exception of portal flow. Direct bilirubin (DB) and alkaline phosphatase (AP) were evaluated in the group BO, BO/DB and CHB.

Results: The bile duct ligation led to an increase of DB and AP, development of liver histological alterations, reduction of portal flow and increase of plasmatic NO and of MDA levels. The bile duct clearing resulted in a reduction of DB, AP, NO, MDA histological alterations and increase of portal flow.

Conclusion: The biliary occlusion resulted in cholestasis and portal flow reduction, besides the increase of plasmatic NO and of hepatic MDA levels, and histological liver alterations, with a tendency of normalization after the bile duct clearing.
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http://dx.doi.org/10.1590/s0102-86502008000700002DOI Listing
June 2009

Endothelium dysfunction classification: why is it still an open discussion?

Int J Cardiol 2009 Oct 3;137(2):175-6. Epub 2008 Aug 3.

In the nineties, the present author developed a didactic endothelium dysfunction classification based on personal experience while waiting for a consensus about the need of such an accomplishment. As time went by and no publications regarding this subject were released, he published a text entitled "An open discussion about endothelial dysfunction: is it timely to propose a classification? Eight years later and the question about endothelium dysfunction classification remains "an open discussion". Nevertheless, we still keep using our proposed classification although always questioning its suitability and wondering reasons for why the scientific communities avoid discussing this very subject. Based on these thoughts we attempted to hypothesize the causes of why this proposed discussion is not an inciting issue: (I) First hypothesis: An endothelium dysfunction classification is not important; (II) Second hypothesis: Such classification is still a "premature reductionism"; (III) Third hypothesis: Endothelium dysfunction is a multifaceted disorder and involves uncountable variations becoming impossible to propose an adequate classification; (IV) Fourth hypothesis: Vasoplegic syndrome and massive nitric oxide release accounts for the functional classification, thus, it seems that cardiovascular journals feel apprehensive about this since their point of view is closely associated with impaired endothelium nitric oxide release as a cause to increased risk of spasm and thrombosis and; (V) Fifth hypothesis: The classification is so fulfilling that it discards the need of discussion or the pioneer attitude to propose such classification has incited some degree of jealousy. Obviously, the fifth hypothesis is pretentiously and overwhelmed, but we again attempt to reopen this discussion because it is time to update the presented classification. In this manner, we are sure that this issue demands special attention of the scientific community. Therefore, the aim of this text is exclusively to "reopen" the discussion about the need of an effective endothelium dysfunction classification.
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http://dx.doi.org/10.1016/j.ijcard.2008.05.031DOI Listing
October 2009

Plasma nitrate/nitrite (NOx) is not a useful biomarker to predict inherent cardiopulmonary bypass inflammatory response.

J Card Surg 2008 Jul-Aug;23(4):336-8

Division of Thoracic and Cardiovascular Surgery, Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine,University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Background And Aim: There were strong evidences that nitric oxide has capital importance in the progressive vasodilatation associated with varied circulatory shock forms, including systemic inflammatory response syndrome (SIRS), in patients undergoing cardiac surgeries for cardiopulmonary bypass (CPB). If CPB procedures, per se, are the inciting stimulus for inflammation, plasma nitrate/nitrite (NOx) excretion would be expected to be higher in these patients rather than in patients operated without CPB. In consequence, we hypothesized that increased levels of NOx would be predictive for vasoplegic syndrome.

Methods: Thirty patients were assigned to three groups: Group 1--coronary artery bypass graft (CABG) roller pump CPB; Group 2--CABG centrifugal vortex pump CPB; and Group 3--heart valve surgery roller pump CPB. Sampling of venous blood for chemiluminescence plasma NOx dosage was achieved at the following time points: (1) before anesthesia induction; (2) after anesthesia induction; (3) before heparin infusion; (4) after heparin infusion; (5) CPB-30 minutes; (6) CPB-60 minutes; (7) before protamine infusion; (8) after protamine infusion; and (9) on return to the recovery area.

Results: There were no intergroup differences regarding age and anesthetic regimen, and the number of arteries grafted was not different between the CABG groups. There were no NOx statistic differences, neither among the three groups of patients or among the surgery time. In addition, there was no correlation among NOx, lactate, and hemoglobin.

Conclusions: Considering the inflammatory process intrinsic to CPB, this study reinforces the idea that plasma NOx is not useful as a biomarker of inflammatory response onset, which may or may not lead to SIRS and/or vasoplegic syndrome.
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http://dx.doi.org/10.1111/j.1540-8191.2008.00649.xDOI Listing
October 2008

Compound 48/80 induces endothelium-dependent and histamine release-independent relaxation in rabbit aorta.

Nitric Oxide 2008 Mar 28;18(2):87-92. Epub 2007 Nov 28.

Department of Surgery and Anatomy, Ribeirão Preto Medical School, São Paulo University, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brazil.

Compound 48/80 (C48/80) is a synthetic condensation product of N-methyl-p-methoxyphenethylamine with formaldehyde and is an experimental drug used since the 1950s to induce anaphylactic shock through histamine release. This study was carried out to further elucidate the mechanism by which this drug induces nitric oxide (NO) release. Our specific goals were: (a) to verify if C48/80's relaxation occurs through the stimulation of histamine receptors; (b) to evaluate the endothelium-dependent relaxation induced by C48/80; (c) to identify NO as the endothelium-relaxing factor released by C48/80; (d) to identify the NO synthase (NOS) responsible for NO release; and (e) to verify if the relaxation induced by C48/80 is calcium and cyclic guanidine monophosphate (cGMP) dependent. Rabbit aorta segments, with and without endothelium, were suspended in organ chambers (25ml) filled with Krebs solution maintained at 37 degrees C, bubbled with 95% O(2)/5% CO(2) (pH 7.4). Phenylephrine was used to contract the segments. Other protocol drugs included H(1)- and H(2)-receptor antagonists, cyclooxygenase, NOS, guanylyl cyclase and phospholipase C (PLC) inhibitors. Endothelium-dependent relaxation induced by C48/80 was also studied in calcium-free Krebs solution associated with a calcium chelator. In summary, our investigation demonstrated that the C48/80 vasodilating action: (a) does not depend on H(1) and H(2) histamine receptors; (b) is NO endothelium-dependent; (c) is dependent on the endothelial constitutive NOS (NOS-3) isoform activation; (d) is cGMP-dependent; and that NOS-3 activation by C48/80: (a) is independent of PLC up to 25mug/ml and (b) is partially dependent of this lipase in higher doses.
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http://dx.doi.org/10.1016/j.niox.2007.11.004DOI Listing
March 2008