Papers by Paulina Sannomiya

Brazilian Journal of Medical and Biological Research, 2007
Neutrophils act as first-line-of-defense cells and the reduction of their functional activity con... more Neutrophils act as first-line-of-defense cells and the reduction of their functional activity contributes to the high susceptibility to and severity of infections in diabetes mellitus. Clinical investigations in diabetic patients and experimental studies in diabetic rats and mice clearly demonstrated consistent defects of neutrophil chemotactic, phagocytic and microbicidal activities. Other alterations that have been reported to occur during inflammation in diabetes mellitus include: decreased microvascular responses to inflammatory mediators such as histamine and bradykinin, reduced protein leakage and edema formation, reduced mast cell degranulation, impairment of neutrophil adhesion to the endothelium and migration to the site of inflammation, production of reactive oxygen species and reduced release of cytokines and prostaglandin by neutrophils, increased leukocyte apoptosis, and reduction in lymph node retention capacity. Since neutrophil function requires energy, metabolic changes (i.e., glycolytic and glutaminolytic pathways) may be involved in the reduction of neutrophil function observed in diabetic states. Metabolic routes by which hyperglycemia is linked to neutrophil dysfunction include the advanced protein glycosylation reaction, the polyol pathway, oxygenfree radical formation, the nitric oxide-cyclic guanosine-3'-5'monophosphate pathway, and the glycolytic and glutaminolytic pathways. Lowering of blood glucose levels by insulin treatment of diabetic patients or experimental animals has been reported to have significant correlation with improvement of neutrophil functional activity. Therefore, changes might be primarily linked to a continuing insulin deficiency or to secondary hyperglycemia occurring in the diabetic individual. Accordingly, effective control with insulin treatment is likely to be relevant during infection in diabetic patients.
Transplant International, 2017
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed São Paulo, Fac Med, Inst Co... more Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed São Paulo, Fac Med, Inst Coracao, Hosp Clin, São Paulo, BrazilUniv Fed São Paulo, Fac Med, Inst Coracao, Hosp Clin, São Paulo, BrazilFAPESP: 2016/03651-0Web of Scienc

Critical Care, 2015
Introduction: Failure to accurately estimate energy requirements may result in an impaired recove... more Introduction: Failure to accurately estimate energy requirements may result in an impaired recovery. Overfeeding has been associated with increased carbon dioxide production, respiratory failure, hyperglycemia and fat deposits in the liver, while underfeeding can lead to malnutrition, muscle weakness and impaired immunity. Objective: This study aimed to determine the metabolic profile of infant and preschool children submitted to mechanical ventilation in the ICU. Methods: A prospective study was carried out in a pediatric ICU in Rio de Janeiro that included children aged from 1 month to 6 years submitted to mechanical ventilation from June 2013 to May 2015. Indirect calorimetry was used to obtain resting energy expenditure (REE) and oxygen consumption (VO 2) in the first 48 hours of admission. The predicted basal metabolic rate (PBMR) was calculated using the Schofield equation. The metabolic state of each patient was assigned as hypermetabolic (REE/PBMR >110%), hypometabolic (REE/PBMR <90%) or normal (REE/PBMR 90-110%). The ratio of caloric intake to REE was also calculated and ratios of >1.5 and <0.5 were classified as overfeeding and underfeeding respectively. Results: A total of 35 infants and 17 preschool children were included. The male/female ratio was 34/18. In respect of severity of sepsis, 19 patients had septic shock, 24 had sepsis, five had severe sepsis and four had systemic inflammatory response syndrome. We observed a high incidence of hypometabolism (88.5%) and a low incidence of normal metabolism (7.7%) and hypermetabolism (3.8%). A low value of VO 2 was observed in 46.1% of the patients (VO 2 ≤120 ml/minute/m 2), a normal value in 40.4% (VO 2 >120 to ≤160 ml/minute/m 2) and a high value in only 13.5% of the patients (VO 2 > 160 ml/minute/m 2). Among the 52 included patients, 18 were fasting at the moment of the examination. The ratio of caloric intake to REE for the remaining 34 patients showed 38.2% overfeeding, 11.8% underfeeding and 50.0% normal feeding. Conclusion: Predictive equations do not accurately predict REE in critically ill infants and preschool children, resulting in inadequate feeding. Although hypermetabolism and enhanced energy expenditure are the main clinical features of critical illness in adults, the majority of our patients were found to be hypometabolic which reinforces the need for a different approach between adult and pediatric critically ill patients.

Interactive CardioVascular and Thoracic Surgery, 2017
OBJECTIVES: Despite research into protective pharmacological adjuncts, paraplegia persists as a d... more OBJECTIVES: Despite research into protective pharmacological adjuncts, paraplegia persists as a dreaded complication after thoracic and thoracoabdominal aortic interventions. Reports on gender-related neurological outcomes after ischaemic and traumatic brain injuries have led to increased interest in hormonal neuroprotective effects and have generated other studies seeking to prove the neuroprotective effects of the therapeutic administration of 17b-oestradiol and of progesterone. We hypothesised that acute administration of oestradiol or progesterone would prevent or attenuate spinal cord ischaemic injury induced by occlusion of the descending thoracic aorta. METHODS: Male rats were divided into groups receiving 280 mg/kg of 17b-oestradiol or 4 mg/kg of progesterone or vehicle 30 min before transitory endovascular occlusion of the proximal descending thoracic aorta for 12 min. Hindlimb motor function was assessed by a functional grading scale (that of Basso, Beattie and Bresnahan) for 14 days after reperfusion. On the 14th day, a segment of the thoracolumbar spinal cord was harvested and prepared for histological and immunohistochemical analyses. RESULTS: There was significant impairment of the motor function of the hindlimb in the 3 study groups, with partial improvement noticed over time, but no difference was detected between the groups. On Day 1 of assessment, the 17b-oestradiol group had a functional score of 9.8 (0.0-16.5); the progesterone group, a score of 0.0 (0-17.1) and the control group, a score of 6.5 (0-16.9); on the 14th day, the 17boestradiol group had a functional score of 18.0 (4.4-19.4); the progesterone group had a score of 7.5 (0-18.5) and the control group had a score of 17.0 (0-19.9). Analysis of the grey matter showed that the number of viable neurons per section was not different between the study groups on the 14th day. Immunostaining of the spinal cord grey matter was also similar among the 3 groups. CONCLUSIONS: Acute administration of oestradiol or of progesterone 30 min before transitory occlusion of the proximal descending thoracic aorta of male rats could not prevent or attenuate spinal cord ischaemic injury based on an analysis of functional and histological outcomes.

Defective leukocyte-endothelial interactions are observed in experimental diabetes mellitus. Endo... more Defective leukocyte-endothelial interactions are observed in experimental diabetes mellitus. Endogenous substances, including nitric oxide (NO), have anti-inflammatory effects within the vasculature by reducing leukocyte adherence to post-capillary venules. The purpose of this study was to examine the activity and expression of NO synthase in neutrophils from alloxan-induced diabetic rats. Glycogen-elicited peritoneal neutrophils were obtained from diabetic rats and matching controls 10, 30, and 180 days after alloxan (42 mg/kg, i.v.) or saline injection. NO synthase activity was determined by the [3H]l-citrulline assay method. Expression of the enzyme was investigated by western blot analysis. Relative to controls, neutrophils obtained from diabetic rats presented a 2-fold increase in the activity of inducible NO synthase (iNOS), accompanied by an increase in the expression of the enzyme depicted by western blot. Treatment of diabetic animals with NPH insulin (2 IU/day, for 3 days)...

Clinics, 2012
OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability... more OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage.
Cellular Physiology and Biochemistry, 2014
This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCo... more This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Inflammation, 1999
Acute thermal trauma is well known to produce evidence of a “systemic inflammatory response” in v... more Acute thermal trauma is well known to produce evidence of a “systemic inflammatory response” in vivo, as manifested by evidence of complement activation, appearance in plasma of a variety of inflammatory factors, and development of multi-organ injury. The current studies were focused on acute thermal injury of rat skin and factors responsible for accompanying activation of blood neutrophils. Acute thermal

Journal of Pharmacy and Pharmacology, 1981
Denervation supersensitivity of the guinea-pig isolated vas deferens is the sum of preand postjun... more Denervation supersensitivity of the guinea-pig isolated vas deferens is the sum of preand postjunctional components (Westfall et al 1972). The prejunctional component, which is cocaine-like, results from the impairment of the neuronal uptake process after degeneration of the adrenergic nerve endings (Trendelenburg 1966). The postjunctional component is caused by alterations of the electrophysiological and/or biochemical properties of the smooth muscle cells and is responsible for the non-specific increase in drug sensitivity (Fleming et al 1973; Fleming 1976). It is generally accepted that decentralization supersensitivity of the guinea-pig vas deferens possesses only the postjunctional component (Westfall et al 1972). Our aim has been to compare the effects of denervation, decentralization and cocaine on the responsiveness of the guinea-pig vas deferens to phenylephrine in vivo and in vitro. The evidence confirms the findings of a recent report (Sannomiya & De Moraes 1979) suggesting the absence of the postjunctional component of denervation supersensitivity to noradrenaline in the guinea-pig vas deferens in experiments performed in vivo. In addition, decentralization-induced supersensitivity to phenylephrine was not demonstrable in the guinea-pig vas deferens in vivo. Guinea-pigs, 350 to 500 g, were anaesthetized with ether and bilateral decentralization was performed by removing 2 cm of the hypogastric nerve (Westfall et al 1972). Unilateral denervation was according to Birmingham (1970). Control animals were shamoperated. In all experiments the animals were used on the 7th day after surgery at a time when postjunctional supersensitivity is fully developed (Westfall 1970). To assess the effectiveness of the decentralization procedure the animals were anaesthetized with ether and the hypogastric nerves, central to the area of transection, were stimulated (I0 Hz, 1 ms duration, 20 V, during IS s). Any vas deferens that contracted was discarded. To reduce the presence of smooth muscle tonus in the in vivo experiments animals were pretreated with reserpine (2 mg kg-') and (&)-a-methylp-tyrosine (250 mg kg-') 24 and 6 h, respectively, before the experiments began. This pretreatment did not interfere with the response of the vasa deferentia of the control group to electrical stimulation. Dose-response curves to phenylephrine were obtained in vivo according to Sannomiya & De Moraes (1977).

Hypertension, 1994
We designed experiments to study the interaction of activated rat peritoneal neutrophils with aor... more We designed experiments to study the interaction of activated rat peritoneal neutrophils with aortas from spontaneously hypertensive rats (SHR) compared with those from normotensive rats. In aortic rings precontracted with phenylephrine, neutrophils obtained from normotensive rats caused a cell number-dependent relaxation of normotensive rat aorta with or without endothelium, whereas relaxation (at lower concentrations) followed by contraction (at higher concentrations) was observed in SHR aorta with endothelium. In SHR aortic rings denuded of endothelium, neutrophils did not induce contraction. The relaxation might be due to a factor indistinguishable from nitric oxide. The contraction might be due to prostaglandin H2 because it was blocked by indomethacin, a cyclooxygenase inhibitor, and ridogrel, a thromboxane A2 synthetase inhibitor/thromboxane A2-prostaglandin H2 antagonist, but not by superoxide dismutase, a superoxide anion scavenger, or dazoxiben, a thromboxane A2 synthetase...

Biochemical Pharmacology, 2001
Defective leukocyte-endothelial interactions are observed in experimental diabetes mellitus. Endo... more Defective leukocyte-endothelial interactions are observed in experimental diabetes mellitus. Endogenous substances, including nitric oxide (NO), have anti-inflammatory effects within the vasculature by reducing leukocyte adherence to post-capillary venules. The purpose of this study was to examine the activity and expression of NO synthase in neutrophils from alloxan-induced diabetic rats. Glycogen-elicited peritoneal neutrophils were obtained from diabetic rats and matching controls 10, 30, and 180 days after alloxan (42 mg/kg, i.v.) or saline injection. NO synthase activity was determined by the [ 3 H]L-citrulline assay method. Expression of the enzyme was investigated by western blot analysis. Relative to controls, neutrophils obtained from diabetic rats presented a 2-fold increase in the activity of inducible NO synthase (iNOS), accompanied by an increase in the expression of the enzyme depicted by western blot. Treatment of diabetic animals with NPH insulin (2 IU/day, for 3 days) reduced both the activity and expression of iNOS to normal levels. Results presented suggest that overexpression of the inducible isoform of NO synthase by neutrophils may be responsible, at least in part, for the defects in leukocyteendothelial interactions in diabetes mellitus.
Arquivos de Neuro-Psiquiatria, 1975
Os AA fazem revisão sobre a unidade motora em seu aspecto morfológico, fisiológico e farmacológic... more Os AA fazem revisão sobre a unidade motora em seu aspecto morfológico, fisiológico e farmacológico como base para o estudo e tratamento da miastenia grave e da síndrome miastênica. Estudos eletromiográficos, farmacológicos e eletrofisiológicos, realizados por diversos autores, determinam características especiais que definem a miastenia grave e a síndrome miastênica. Certos sinais e sintomas, comumente observados em casos de envenenamento por elapídeos, são semelhantes aos causados por drogas bloqueadoras neuromusculares.
Revista de Medicina, 2015
XXXIV COMU-Congresso Médico Universitário da FMUSP Trabalhos Classificados-Prêmio Painéis-Área Bá... more XXXIV COMU-Congresso Médico Universitário da FMUSP Trabalhos Classificados-Prêmio Painéis-Área Básica Avaliação dos efeitos do 17β-estradiol na lesão mesentérica induzida pela oclusão da porção proximal da aorta descendente em ratos machos
Critical Care Medicine, 2001
Uploads
Papers by Paulina Sannomiya