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1.
Sci Rep ; 14(1): 8215, 2024 04 08.
Article in English | MEDLINE | ID: mdl-38589479

ABSTRACT

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.


Subject(s)
Agaricus , Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Animals , Rats , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology , Diphosphonates , Maxilla/pathology , Tooth Extraction , Wnt Signaling Pathway , Zoledronic Acid
2.
J Dent (Shiraz) ; 25(1): 59-67, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38544779

ABSTRACT

Statement of the Problem: Periodontitis is an inflammatory disease that causes bone loss. Some patients do not respond well to the classic treatment and need therapies that minimize bone loss, the main sequel of the disease. Chenopodium ambrosioides L. has stood out due to its anti-inflammatory and anti-oxidative activities. However, no study has yet investigated its effect on periodontitis. Purpose: This study aimed to evaluate the bone protective effect of Chenopodium ambrosioides L. (CAL) extract on ligature-induced periodontitis model in rats. Materials and Method: For this, a pre-clinical assay was performed, using male Wistar rats divided into 3 groups: Naive (N) (n=6), not submitted to any procedure; Saline (SAL) (n=6), submitted to ligature-induced periodontitis and receiving 2 ml/kg of 0.9% saline solution; and CAL extract, which was subdivided into 3 subgroups (n=6/subgroup) receiving the CAL at 3 (CAL3), 10 (CAL10) or 30 mg/kg (CAL30). All agents were given, by oral gavage, 30 min before periodontitis induction and daily until euthanasia (11th day). By then, maxillae were removed for macroscopic, histological, and histometric analyses. Kidneys, liver, and stomach were collected to evaluate the safety of CAL extract. High-performance liquid chromatography (HPLC) assay was used to investigate the flavonoid content in the extract. Results: Chenopodium ambrosioides L. extract at 30mg/kg showed a reduction by 58% in bone loss marked by an increase (+35%) in the number of osteoblasts and a reduction (-51%) on the number of osteoclasts (p< 0.05). No significant alteration in the liver, kidney, or stomach was seen. Rutin was the main flavonoid found. Conclusion: In summary, it was observed that Chenopodium ambrosioides L. extract has shown important anti-inflammatory and bone anabolic and anti-resorptive properties without causing toxicity in the main organs. Rutin, as the main flavonoid of the extract, seems to be responsible for the beneficial effect of this agent.

3.
Clin Oral Investig ; 22(6): 2175-2185, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29288400

ABSTRACT

OBJECTIVE: The aim of this work was to evaluate the anti-inflammatory and antiresorptive effects of Calendula officinalis (CLO) on alveolar bone loss (ABL) in rats. MATERIAL AND METHODS: Male Wistar rats were subjected to ABL by ligature with nylon thread around the second upper left molar. The contralateral hemimaxillae were used as control. Rats received saline solution (SAL) or CLO (10, 30, or 90 mg/kg) 30 min before ligature and daily until the 11th day. The maxillae were removed and prepared for macroscopic, radiographic, micro-tomographic, histopathologic, histometric analysis, and immunohistochemical localization of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). The gingival tissues were used to quantify the myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1ß (IL-1ß) concentrations by ELISA. Blood samples were collected for leukogram and to evaluate the bone-specific alkaline phosphatase (BALP) activity and serum levels of aspartate and alanine transaminases (AST/ALT). RESULTS: The bone loss induced by 11 days of ligature induced bone loss, reduced levels of BALP, leukocyte infiltration, increased MPO activity, gingival concentrations of TNF-α and IL-1ß, and RANKL while reduced OPG immunoexpressions in the periodontal tissue and leukocytosis. Of the CLO, 90 mg/kg reduced bone loss, neutrophilia, the levels of pro-inflammatory mediators, and RANKL expression, while it increased OPG immunopositive cells and BALP serum levels, when compared to SAL. CLO did not affect either kidney or liver function, indicated by serum AST/ALT levels. CONCLUSION: The present data suggests that CLO reduced inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti-inflammatory properties and its effects on bone metabolism. CLINICAL RELEVANCE: CLO can be a potential therapeutical adjuvant in the treatment of periodontitis.


Subject(s)
Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/metabolism , Calendula , Plant Extracts/pharmacology , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Biomarkers/metabolism , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Interleukin-1beta/metabolism , Ligation , Male , Maxilla , Molar , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism
4.
J Cachexia Sarcopenia Muscle ; 8(1): 89-101, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27897405

ABSTRACT

BACKGROUND: The 'obesity paradox' of critical illness refers to better survival with a higher body mass index. We hypothesized that fat mobilized from excess adipose tissue during critical illness provides energy more efficiently than exogenous macronutrients and could prevent lean tissue wasting. METHODS: In lean and premorbidly obese mice, the effect of 5 days of sepsis-induced critical illness on body weight and composition, muscle wasting, and weakness was assessed, each with fasting and parenteral feeding. Also, in lean and overweight/obese prolonged critically ill patients, markers of muscle wasting and weakness were compared. RESULTS: In mice, sepsis reduced body weight similarly in the lean and obese, but in the obese with more fat loss and less loss of muscle mass, better preservation of myofibre size and muscle force, and less loss of ectopic lipids, irrespective of administered feeding. These differences between lean and obese septic mice coincided with signs of more effective hepatic fatty acid and glycerol metabolism, and ketogenesis in the obese. Also in humans, better preservation of myofibre size and muscle strength was observed in overweight/obese compared with lean prolonged critically ill patients. CONCLUSIONS: During critical illness premorbid obesity, but not nutrition, optimized utilization of stored lipids and attenuated muscle wasting and weakness.


Subject(s)
Critical Illness , Muscle Weakness , Muscular Atrophy , Overweight , Sepsis , 3-Hydroxybutyric Acid/blood , Aged , Animals , Body Composition , Fasting/metabolism , Fatty Acids/blood , Female , Glycerol/blood , Humans , Liver/metabolism , Male , Mice, Inbred C57BL , Middle Aged , Muscle Proteins/genetics , Muscle Proteins/metabolism , Muscle Weakness/metabolism , Muscle Weakness/pathology , Muscular Atrophy/metabolism , Muscular Atrophy/pathology , Nutritional Status , Overweight/metabolism , Overweight/pathology , Parenteral Nutrition , Quadriceps Muscle/anatomy & histology , Quadriceps Muscle/metabolism , Quadriceps Muscle/physiology , Rectus Abdominis/anatomy & histology , Rectus Abdominis/metabolism , Rectus Abdominis/physiology , Sepsis/metabolism , Sepsis/pathology , Triglycerides/metabolism
5.
J Periodontol ; 87(10): 1206-16, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27240474

ABSTRACT

BACKGROUND: Atorvastatin (ATV) has shown pleiotropic effects on bone tissue, and osteoporosis can aggravate periodontitis. Thus, the effects of ATV on experimental periodontitis (EP) in rats subjected to glucocorticoid-induced osteoporosis (GIOP) was assessed. METHODS: Male Wistar rats were divided into the following groups: 1) naive; 2) EP; 3) GIOP + EP; and 4) ATV. Groups GIOP + EP and ATV received 7 mg/kg dexamethasone intramuscularly once per week for 5 weeks, and the others received saline (SAL). Groups EP, GIOP + EP, and ATV were submitted to EP by ligature around the maxillary left second molars for 11 days. Group ATV received 27 mg/kg ATV orally, and the others received SAL 30 minutes before EP. Periodontium was analyzed by macroscopy, microtomography, and histopathology; by immunohistochemical examination of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), wingless (WNT) 10b, dickkopf-related protein 1 (DKK-1), and ß-catenin; and by enzyme-linked immunosorbent assay analysis of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, IL10, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Leukogram, liver and kidney enzymes, and bone-specific alkaline phosphatase (BALP) serum levels were evaluated. RESULTS: ATV decreased bone loss, reduced MPO, TNF-α, IL-1ß, IL-6, and IL-8, and increased IL-10, GSH, SOD, and CAT levels. ATV reduced RANKL and DKK-1 and increased OPG, WNT10b, and ß-catenin expressions and BALP activity. CONCLUSION: ATV reduced inflammation, oxidative stress, and bone loss in rats with EP and GIOP, with participation of the WNT signaling pathway.


Subject(s)
Atorvastatin/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Osteoporosis/drug therapy , Periodontitis/drug therapy , Alveolar Bone Loss , Animals , Gene Expression/drug effects , Glucocorticoids , Male , Osteoporosis/complications , Periodontitis/etiology , Rats , Rats, Wistar
6.
Shock ; 44(3): 245-51, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26009823

ABSTRACT

Glucose toxicity may play a crucial role in evoking neurologic complications of critical illness. We studied whether the neuropathological alterations in fatal human critical illness observed under hyperglycemia are present and can be attenuated by maintaining normoglycemia in a mouse model of prolonged sepsis induced by cecal ligation and puncture. Mice were randomized to moderate hyperglycemia (>8.3 mmol/L, n = 8) or normoglycemia (4.4-6.7 mmol/L, n = 8). After 5 days, hippocampus and frontal cortex from septic mice were compared with those from healthy controls (n = 8). Blood glucose was 7.8 ± 1.3 mmol/L in hyperglycemic and 6.1 ± 0.7 mmol/L in normoglycemic critically ill mice (P = 0.007). The percentage of damaged neurons was twofold higher in frontal cortex (P = 0.01) and hippocampus (P = 0.06) of hyperglycemic ill mice than that of healthy mice. In frontal cortex, neuronal damage was attenuated under normoglycemia (P = 0.04). Critical illness reduced astrocyte density and activation status fourfold in hippocampus (P ≤ 0.02), but not in frontal cortex, irrespective of glycemic control. Microglia were twofold to fourfold more abundant in both brain areas of hyperglycemic critically ill mice (P ≤ 0.002), but only in frontal cortex were they reduced in number with normoglycemia (P = 0.0008). The density of apoptotic cells and abundance of carbonylated proteins were significantly higher than normal in frontal cortex of hyperglycemic ill mice only (P = 0.05). In a mouse model of prolonged polymicrobial sepsis, remarkable neuropathological changes develop with neuronal damage, impaired astrocyte activation, increased microglia, apoptosis, and accumulation of carbonylated proteins. These changes were partially prevented or attenuated when hyperglycemia was prevented with insulin. Frontal cortex appeared more vulnerable to hyperglycemic insults than hippocampus.


Subject(s)
Frontal Lobe/pathology , Hippocampus/pathology , Hyperglycemia/pathology , Sepsis/pathology , Animals , Apoptosis , Astrocytes/pathology , Blood Glucose/metabolism , Hyperglycemia/blood , Hyperglycemia/microbiology , Male , Mice, Inbred C57BL , Microglia/pathology , Sepsis/blood , Sepsis/complications
7.
J Renin Angiotensin Aldosterone Syst ; 16(3): 481-7, 2015 Sep.
Article in English | MEDLINE | ID: mdl-23950549

ABSTRACT

INTRODUCTION: adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor, and it has recently been suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating the AMPK system. This study aimed to evaluate the effects of candesartan, an angiotensin II receptor blocker, on cardiac and hepatic AMPK activity basally as well as after surgical stress under general anesthesia. MATERIALS AND METHODS: Male Wistar rats were treated with 5 mg/kg/day candesartan in their drinking water for two weeks. Levels of cardiac and hepatic AMPK activity were determined, using a kinase activity assay, basally and after surgical stress under general anesthesia. RESULTS: Chronic administration of candesartan increased hepatic AMPK activity approximately 4 times (p<0.05) while no significant change was demonstrated in cardiac AMPK. Cardiac and hepatic AMPK activities were not significantly increased by surgical stress alone performed under anesthesia. However, chronic treatment with candesartan decreased AMPK activity in both liver and heart after surgical stress under anesthesia (p<0.01 for both comparisons). CONCLUSIONS: While chronic candesartan treatment may stimulate AMPK activity in certain organs such as the liver, when combined with surgical stress under anesthesia it inhibits pathways regulating AMPK activity.


Subject(s)
Adenylate Kinase/metabolism , Benzimidazoles/pharmacology , Laparotomy , Liver/enzymology , Myocardium/enzymology , Stress, Physiological , Tetrazoles/pharmacology , Animals , Benzimidazoles/administration & dosage , Biphenyl Compounds , Liver/drug effects , Male , Rats, Wistar , Stress, Physiological/drug effects , Tetrazoles/administration & dosage
8.
Crit Care ; 17(5): R193, 2013 Sep 10.
Article in English | MEDLINE | ID: mdl-24020372

ABSTRACT

INTRODUCTION: We previously reported that in artificially-fed critically ill patients, adipose tissue reveals an increase in small adipocytes and accumulation of M2-macrophages. We hypothesized that nutrient-independent factors of critical illness explain these findings, and that the M2-macrophage accumulation may not be limited to adipose tissue. METHODS: In a long-term cecal ligation and puncture (CLP) mouse model of sepsis, we compared the effect of parenteral nutrition (CLP-fed, n = 13) with nutrient restriction (CLP-restricted, n = 11) on body composition, adipocyte size and macrophage accumulation in adipose tissue, liver and lungs. Fed healthy mice (n = 11) were studied as controls. In a human study, in vivo adipose tissue biopsies were studied from ICU patients (n = 40) enrolled in a randomized control trial which compared early initiation of parenteral nutrition (PN) versus tolerating nutrient restriction during the first week of ICU stay. Adipose tissue morphology was compared with healthy human controls (n = 13). RESULTS: Irrespective of nutritional intake, critically ill mice lost weight, fat and fat-free mass. Adipocyte number, proliferation marker Proliferating Cell Nuclear Antigen (PCNA) and adipogenic markers PPARγ and CCAAT/enhancer binding protein-ß (C/EBPß) increased with illness, irrespective of nutritional intake. M2-macrophage accumulation was observed in adipose tissue, liver and lungs of critically ill mice. Macrophage M2-markers correlated with CCL2 expression. In adipose tissue biopsies of critically ill patients, increased adipogenic markers and M2 macrophage accumulation were present irrespective of nutritional intake. CONCLUSIONS: Adipogenesis and accumulation of tissue M2-macrophages are hallmarks of prolonged critical illness, irrespective of nutritional management. During critical illness, M2-macrophages accumulate not only in adipose tissue, but also in the liver and lungs.


Subject(s)
Adipogenesis/physiology , Adipose Tissue/metabolism , Critical Illness , Macrophage Activation/physiology , Macrophages/metabolism , Nutritional Status/physiology , Adipose Tissue/pathology , Aged , Animals , Female , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged
9.
J Clin Endocrinol Metab ; 98(3): 1006-13, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23348400

ABSTRACT

CONTEXT: Both critical illness and fasting induce low circulating thyroid hormone levels in the absence of a rise in TSH, a constellation-labeled nonthyroidal illness syndrome (NTI). The contribution of restricted nutrition during critical illness in the pathophysiology of NTI remains unclear. OBJECTIVE: The objective of the study was to investigate the impact of nutrient restriction early during critical illness on the NTI, in relation to outcome. DESIGN AND PATIENTS: A preplanned subanalysis in a group of intensive care unit (ICU) patients admitted after complicated surgery and for whom enteral nutrition was contraindicated (n = 280) of a randomized controlled trial, which compared tolerating pronounced nutritional deficit for 1 week in the ICU [late parenteral nutrition (PN)] with early initiation of parenteral nutrition (early PN). MEASUREMENTS: Circulating TSH, total T4, T3, rT3, and leptin levels were quantified upon admission and on ICU day 3 or the last day when patients were discharged earlier. After correction for baseline risk factors, the role of these changes from baseline in explaining the outcome benefit of late PN was assessed with the multivariable Cox proportional hazard analysis. RESULTS: Late PN reduced complications and accelerated recovery. Circulating levels of TSH, total T4, T3, the T3 to rT3 ratio, and leptin levels were all further reduced by late PN. The further lowering of T4 appeared to reduce the outcome benefit of late PN, whereas the further reduction of T3 to rT3 ratio appeared to statistically explain part of the outcome benefit. CONCLUSIONS: Tolerating nutrient restriction early during critical illness, shown to accelerate recovery, further aggravated the NTI. The statistical analyses suggested that the more pronounced peripheral inactivation of the thyroid hormone with nutrient restriction during critical illness could be a beneficial adaptation, whereas the lowering of T4 could be deleterious.


Subject(s)
Critical Care/methods , Critical Illness/therapy , Food Deprivation/physiology , Parenteral Nutrition/methods , Thyroid Gland/physiology , Aged , Critical Illness/epidemiology , Fasting/physiology , Female , Humans , Leptin/blood , Male , Middle Aged , Parenteral Nutrition/adverse effects , Proportional Hazards Models , Prospective Studies , Recovery of Function/physiology , Risk Factors , Thyrotropin/blood , Thyroxine/blood , Treatment Outcome , Triiodothyronine/blood
10.
Crit Care Med ; 41(1): 317-25, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23135416

ABSTRACT

OBJECTIVE: Observational studies report lower mortality in obese than in lean critically ill patients, an association referred to as the "obesity paradox." This may suggest a possible protective role for adipose tissue during severe illness. DATA SOURCES: Relevant publications were identified based on searches in PubMed and on secondary searches of their bibliographies. DATA SYNTHESIS: The endocrine functions of adipose tissue might play a role in the adaptation to critical illness. In the acute phase of illness, the anti-inflammatory adiponectin is reduced, whereas proinflammatory cytokine expression in adipose tissue is up-regulated. In the prolonged phase of critical illness, both adiponectin and anti-inflammatory cytokine production are increasing. Studies on the proinflammatory adipokine leptin during critical illness are inconsistent, possibly due to confounders such as gender, body mass index, and feeding. Morphologically, adipose tissue of critically ill patients reveals an increased number of newly differentiated, smaller adipocytes. Accentuated macrophage accumulation showing a phenotypic switch to M2-type suggests an adaptive response to the microenvironment of severe illness. Functionally, adipose tissue of critically ill patients develops an increased ability to store glucose and triglycerides. CONCLUSIONS: Endocrine, metabolic, and morphologic properties of adipose tissue change during critical illness. These alterations may suggest a possible adaptive, protective role in optimizing chances of survival. More research is needed to understand the exact role of adipose tissue in lean vs. obese critically ill patients, in order to understand how illness-associated alterations contribute to the obesity paradox.


Subject(s)
Adipose Tissue/metabolism , Critical Illness , Endocrine System/metabolism , Adaptation, Physiological , Adipocytes/metabolism , Adiponectin/metabolism , Adipose Tissue/immunology , Adipose Tissue/physiopathology , Body Mass Index , Critical Illness/mortality , Cytokines/metabolism , Endocrine System/immunology , Endocrine System/physiopathology , Energy Metabolism , Humans , Leptin/metabolism , Macrophage Activation , Obesity/metabolism
11.
Stress ; 15(5): 554-61, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22217206

ABSTRACT

5' adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor. The role of hypothalamic AMPK in response to restraint and surgical stress has not been previously investigated. It has been recently suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating metabolic pathways including the regulation of the AMPK system. This study was thus aimed to evaluate the effects of candesartan, an angiotensin II AT1 receptor blocker drug, on hypothalamic AMPK activity under basal conditions and after restraint in conscious rats or after surgical stress under general anesthesia. Male Wistar rats were treated with 5 mg/kg/day candesartan in the drinking water for 2 weeks. The hypothalamic AMPK activity was determined under basal and stress conditions, using a kinase activity assay. Chronic administration of candesartan significantly increased hypothalamic AMPK activity. Hypothalamic AMPK activity was also increased by restraint stress whereas no change was observed during surgical stress under anesthesia. The high levels of hypothalamic AMPK activation observed in candesartan-treated rats were not changed by restraint stress but were reduced to control levels by anesthesia and surgery. In conclusion, chronic candesartan treatment and restraint stress in conscious rats stimulate the hypothalamic AMPK activity, whereas surgical stress under anesthesia inhibits pathways regulating the AMPK activity even in candesartan-treated rats.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Angiotensin II Type 1 Receptor Blockers/pharmacology , Benzimidazoles/pharmacology , Hypothalamus/drug effects , Stress, Physiological , Tetrazoles/pharmacology , Animals , Biphenyl Compounds , Hypothalamus/metabolism , Male , Rats , Rats, Wistar , Renin-Angiotensin System/drug effects
12.
Crit Care ; 15(5): R245, 2011.
Article in English | MEDLINE | ID: mdl-22018099

ABSTRACT

INTRODUCTION: We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown. METHODS: We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients. RESULTS: Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels. CONCLUSIONS: Unlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2 macrophages, which have local anti-inflammatory and insulin sensitizing features. This M2 macrophage accumulation may contribute to the previously observed protective metabolic activity of adipose tissue during critical illness.


Subject(s)
Adipose Tissue/chemistry , Critical Illness , Macrophage Activation , Macrophages/chemistry , Adipose Tissue/cytology , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Case-Control Studies , Female , Humans , Male , Middle Aged
13.
Rev. bras. anestesiol ; 61(4): 462-468, jul.-ago. 2011. tab
Article in Portuguese | LILACS | ID: lil-593242

ABSTRACT

JUSTIFICATIVA E OBJETIVOS: É necessário proceder a relaxamento cerebral durante cirurgia intracraniana e a terapia hiperosmolar é uma das medidas para sua produção. Com frequência, pacientes neurocirúrgicos apresentam distúrbios de sódio. O objetivo deste trabalho foi quantificar e determinar o relaxamento cerebral e a duração das alterações hidroeletrólíticas decorrentes do uso do manitol versus solução isoncótica hipertônica (SIH) durante neurocirurgia. MÉTODO: Foram avaliados relaxamento cerebral e alterações hidroeletrolíticas de 29 pacientes adultos antes, 30 e 120 minutos após o término da infusão de carga aproximadamente equiosmolar de manitol 20 por cento (250 mL) ou SIH (120 mL). Registraram-se volume de líquidos intravenosos infundidos e diurese. Considerou-se p < 0,05 como significativo. RESULTADOS: Não houve diferença estatística significativa entre os dois grupos quanto ao relaxamento cerebral. Embora várias diferenças nos eletrólitos e no equilíbrio ácido-básico com o uso de manitol ou SIH tenham alcançado significância estatística, apenas a redução do sódio plasmático, 30 minutos após o uso do manitol, em média de 6,42 ± 0,40 mEq.L-1 e a elevação do cloro em média 5,41 ± 0,96 mEq.L-1 e 5,45 ± 1,45 mEq.L-1, 30 e 120 minutos, respectivamente, após a SIH deslocaram transitoriamente os níveis séricos desses íons da faixa de normalidade laboratorial. O grupo do manitol (20 por cento) apresentou diurese significativamente maior nos dois tempos estudados em comparação com o grupo da SIH. CONCLUSÕES: Solução salina isoncótica hipertônica [NaCl 7,2 por cento/HES (200/0,5) 6 por cento] e manitol (20 por cento), em dose única com cargas osmolares equivalentes, foram efetivos e seguros em produzir relaxamento cerebral durante os procedimentos neurocirúrgicos eletivos sob anestesia geral.


BACKGROUND AND OBJECTIVE: Cerebral relaxation during intracranial surgery is necessary, and hiperosmolar therapy is one of the measures used to this end. Frequently, neurosurgical patients have sodium imbalances. The objective of the present study was to quantify and determine cerebral relaxation and duration of hydroelectrolytic changes secondary to the use of mannitol versus hypertonic isoncotic solution (HIS) during neurosurgery. METHODS: Cerebral relaxation and hydroelectrolytic changes were evaluated in 29 adult patients before de beginning of infusion, and 30 and 120 minutes after the infusion of equiosmolar loads of approximately 20 percent mannitol (250 mL) or HIS (120 mL). The volume of intravenous fluids infused and diuresis were recorded. A p < 0.05 was considered significant. RESULTS: A statistically significant difference in cerebral relaxation between both groups was not observed. Although several changes in electrolyte levels and acid-base balance with mannitol or HIS reached statistical significance only the reduction in plasma sodium 30 minutes after infusion of mannitol, mean of 6.42 ± 0.40 mEq.L-1, and the increase in chloride, mean of 5.41 ± 0.96 mEq.L-1 and 5.45 ± 1.45 mEq.L-1 30 and 120 minutes after infusion of HIS, caused a transitory dislocation of serum ion levels from normal range. The mannitol (20 percent) group had a significantly greater diuresis at both times studied compared with HIS group. CONCLUSIONS: A single dose of hypertonic isoncotic saline solution [7.2 percent NaCl/6 percent HES (200/0.5)] and mannitol (20 percent) with equivalent osmolar loads were effective and safe in producing cerebral relaxation during elective neurosurgical procedures under general anesthesia.


JUSTIFICATIVA Y OBJETIVOS: La relajación cerebral es necesaria durante la cirugía intracraneana, y la terapia hiperosmolar es una de las medidas para su producción. Los pacientes neuroquirúrgicos a menudo presentan disturbios del sodio. El objetivo del trabajo fue cuantificar y determinar la relajación cerebral y la duración de las alteraciones hidroelectrolíticas provenientes del uso del manitol versus solución isoncótica hipertónica (SIH), durante la neurocirugía. MÉTODO: Se evaluaron la relajación cerebral y las alteraciones hidroelectrolíticas de 29 pacientes adultos antes, 30 y 120 min después del término de la infusión de carga aproximadamente equiosmolar de manitol 20 por ciento (250 mL) o SIH (120 mL). Se registró el volumen de los líquidos intravenosos infundidos y la diuresis. El P < 0,05 fue considerado significativo. RESULTADOS: No hubo ninguna diferencia estadística significativa entre los dos grupos en cuanto a la relajación cerebral. Aunque varias diferencias en los electrólitos y el equilibrio ácido-básico con el uso de manitol o SIH, hayan alcanzado una significancia estadística, solamente la reducción del sodio plasmático 30 min después del uso del manitol, como promedio de 6,42 ± 0,40 mEq.L-1, y la elevación del cloro como promedio 5,41 ± 0,96 mEq.L-1 y 5,45 ± 1,45 mEq.L-1, 30 y 120 min respectivamente después de la SIH, alteraron transitoriamente los niveles séricos de esos iones del rango de la normalidad laboratorial. El grupo del manitol (20 por ciento) tuvo una diuresis significativamente mayor en los dos tiempos estudiados en comparación con el grupo de la SIH. CONCLUSIONES: La solución salina isoncótica-hipertónica [NaCl 7,2 por ciento/HES (200/0,5) 6 por ciento] y manitol (20 por ciento), en dosis única con carga osmolar equivalente, fueron efectivos y seguros para generar la relajación cerebral durante los procedimientos neuroquirúrgicos electivos bajo la anestesia general.


Subject(s)
Humans , Saline Solution/pharmacology , Anesthesia, General/instrumentation , Mannitol/pharmacology , Neurosurgery/instrumentation
14.
Rev Bras Anestesiol ; 61(4): 456-68, 2011.
Article in English, Mul | MEDLINE | ID: mdl-21724008

ABSTRACT

BACKGROUND AND OBJECTIVES: Cerebral relaxation during intracranial surgery is necessary, and hiperosmolar therapy is one of the measures used to this end. Frequently, neurosurgical patients have sodium imbalances. The objective of the present study was to quantify and determine cerebral relaxation and duration of hydroelectrolytic changes secondary to the use of mannitol versus hypertonic isoncotic solution (HIS) during neurosurgery. METHODS: Cerebral relaxation and hydroelectrolytic changes were evaluated in 29 adult patients before de beginning of infusion, and 30 and 120 minutes after the infusion of equiosmolar loads of approximately 20% mannitol (250 mL) or HIS (120 mL). The volume of intravenous fluids infused and diuresis were recorded. A p < 0.05 was considered significant. RESULTS: A statistically significant difference in cerebral relaxation between both groups was not observed. Although several changes in electrolyte levels and acid-base balance with mannitol or HIS reached statistical significance only the reduction in plasma sodium 30 minutes after infusion of mannitol, mean of 6.42 ± 0.40 mEq.L(-1), and the increase in chloride, mean of 5.41 ± 0.96 mEq.L(-1) and 5.45 ± 1.45 mEq.L(-1) 30 and 120 minutes after infusion of HIS, caused a transitory dislocation of serum ion levels from normal range. The mannitol (20%) group had a significantly greater diuresis at both times studied compared with HIS group. CONCLUSIONS: A single dose of hypertonic isoncotic saline solution [7.2% NaCl/6% HES (200/0.5)] and mannitol (20%) with equivalent osmolar loads were effective and safe in producing cerebral relaxation during elective neurosurgical procedures under general anesthesia.


Subject(s)
Anesthesia , Brain/surgery , Craniotomy , Diuretics, Osmotic/therapeutic use , Hypertonic Solutions/therapeutic use , Mannitol/therapeutic use , Water-Electrolyte Balance , Adult , Female , Humans , Male
15.
Rev Bras Anestesiol ; 58(6): 623-30, 2008.
Article in English, Portuguese | MEDLINE | ID: mdl-19082409

ABSTRACT

BACKGROUND AND OBJECTIVES: Tako-Tsubo syndrome is a rare postoperative complication with a 5% mortality rate. The objective of this report was to present residual neuromuscular blockade as a trigger for this syndrome, discuss this disorder, and call attention to the risks of residual neuromuscular blockade. CASE REPORT: A 61-year old female, physical status ASA I, who underwent general anesthesia associated with paravertebral cervical block for arthroscopic repair of a rotator cuff lesion. Physical exam after extubation detected residual neuromuscular blockade. In the post-anesthetic care unit the patient developed somnolence, tachycardia, hypertension, and severe respiratory acidosis. After reintubation the patient evolved for cardiac arrest with electrical activity without a pulse, which was reverted with the administration of adrenaline and external cardiac massage. In the postoperative period the patient presented elevation of the ST segment, increased troponin, and left ventricular medial-apical akinesia with an estimated ejection fraction of 30%. Cardiac catheterization showed absence of significant atheromatous lesions in the coronary vessels, and severe disruption of the systolic function with inferior and antero-septo-apical akinesia and compensatory basal hypercontractility. The patient had complete functional recovery with the treatment instituted. CONCLUSIONS: Residual neuromuscular blockade associated with diaphragmatic paralysis and possible pulmonary atelectasis leading to respiratory failure, hypercapnia, and adrenergic discharge triggered the Tako-Tsubo syndrome with severe clinical repercussion.


Subject(s)
Nerve Block/adverse effects , Takotsubo Cardiomyopathy/etiology , Female , Humans , Middle Aged
16.
Rev. bras. anestesiol ; 58(6): 623-630, nov.-dez. 2008. ilus
Article in English, Portuguese | LILACS | ID: lil-497049

ABSTRACT

JUSTIFICATIVA E OBJETIVOS: A síndrome de Tako-Tsubo é uma complicação pós-operatória rara, com mortalidade em torno de 5 por cento. O objetivo deste relato é apresentar o bloqueio neuromuscular residual como fator desencadeante da referida síndrome, discutir sobre a mesma e alertar sobre o bloqueio neuromuscular residual. RELATO DO CASO: Paciente do sexo feminino, 61 anos, estado físico ASA I, submetida à anestesia geral associada a bloqueio paravertebral cervical para reparo artroscópico de lesão de manguito rotator. Após extubação foi evidenciado bloqueio neuromuscular residual por meio do exame clínico. Na sala de recuperação pós-anestésica evoluiu com sonolência, taquicardia, hipertensão arterial e acidose respiratória grave. Após a reintubação, evoluiu com parada cardíaca em atividade elétrica sem pulso, revertida com adrenalina e massagem cardíaca externa. Apresentou no pós-operatório elevação de segmento ST, aumento de troponina e acinesia de segmento médio-apical de ventrículo esquerdo com fração de ejeção estimada em 30 por cento. A cineangiocoronariografia mostrou coronárias isentas de ateromatose significativa e grave comprometimento da função sistólica com acinesia inferior e ântero-septo-apical com hipercontratilidade compensatória de suas porções basais. Com o tratamento instituído houve recuperação funcional completa. CONCLUSÕES: O bloqueio neuromuscular residual associado à paralisia diafragmática e possível atelectasia pulmonar levando a insuficiência respiratória, hipercapnia e descarga adrenérgica foram os fatores desencadeantes da síndrome de Tako-Tsubo com sua grave repercussão clínica.


BACKGROUND AND OBJECTIVES: Tako-Tsubo syndrome is a rare postoperative complication with a 5 percent mortality rate. The objective of this report was to present residual neuromuscular blockade as a trigger for this syndrome, discuss this disorder, and call attention to the risks of residual neuromuscular blockade. CASE REPORT: A 61-year old female, physical status ASA I, who underwent general anesthesia associated with paravertebral cervical block for arthroscopic repair of a rotator cuff lesion. Physical exam after extubation detected residual neuromuscular blockade. In the post-anesthetic care unit the patient developed somnolence, tachycardia, hypertension, and severe respiratory acidosis. After reintubation the patient evolved for cardiac arrest with electrical activity without a pulse, which was reverted with the administration of adrenaline and external cardiac massage. In the postoperative period the patient presented elevation of the ST segment, increased troponin, and left ventricular medial-apical akinesia with an estimated ejection fraction of 30 percent. Cardiac catheterization showed absence of significant atheromatous lesions in the coronary vessels, and severe disruption of the systolic function with inferior and antero-septo-apical akinesia and compensatory basal hypercontractility. The patient had complete functional recovery with the treatment instituted. CONCLUSIONS: Residual neuromuscular blockade associated with diaphragmatic paralysis and possible pulmonary atelectasis leading to respiratory failure, hypercapnia, and adrenergic discharge triggered the Tako-Tsubo syndrome with severe clinical repercussion.


JUSTIFICATIVA Y OBJETIVOS: El Síndrome de Tako-Tsubo es una complicación postoperatoria rara con una mortalidad en torno de un 5 por ciento. El objetivo de este relato es presentar el bloqueo neuromuscular residual como factor desencadenante del referido síndrome, discutir sobre él y alertar sobre el bloqueo neuromuscular residual. RELATO DEL CASO: Paciente del sexo femenino, 61 años, estado físico ASA I, sometida a la anestesia general asociada al bloqueo paravertebral cervical para la reparación artroscópica de lesión de manguito de los rotadores. Después de la extubación, quedó demostrado el bloqueo neuromuscular residual a través del examen clínico. En la sala de recuperación postanestésica, evolucionó con somnolencia, taquicardia, hipertensión arterial y acidosis respiratoria grave. Después de la reintubación evolucionó con parada cardíaca en actividad eléctrica sin pulso, revertida con adrenalina y masaje cardíaco externo. En el postoperatorio presentó una elevación de segmento ST, aumento de troponina y acinesia de segmento medio-apical del ventrículo izquierdo, con fracción de eyección estimada en un 30 por ciento. La cineangiocoronariografía mostró coronarias exentas de ateromatosis significativa y un grave comprometimiento de la función sistólica con acinesia inferior y ántero-septo-apical, con hipercontratilidad compensatoria de sus porciones basales. Con el tratamiento iniciado, hubo una recuperación funcional completa. CONCLUSIONES: El bloqueo neuromuscular residual asociado a la parálisis diafragmática y la posible atelectasia pulmonar, que conlleva a la insuficiencia respiratoria, hipercapnia y descarga adrenérgica, fueron los factores desencadenantes del síndrome de Tako-Tsubo con su grave repercusión clínica.


Subject(s)
Humans , Female , Middle Aged , Neuromuscular Blockade/adverse effects , Takotsubo Cardiomyopathy/etiology
17.
Rev. bras. anestesiol ; 56(6): 654-657, nov.-dez. 2006.
Article in Portuguese | LILACS | ID: lil-447140

ABSTRACT

JUSTIFICATIVA E OBJETIVOS: Durante uma craniotomia em que se realiza o teste de Afasia de Aachen com o paciente acordado e cooperativo, é necessário o uso da técnica anestésica "dormindo-acordado-dormindo". O objetivo deste relato de caso foi descrever a técnica anestésica utilizada em paciente com sinais de via aérea difícil. RELATO DO CASO: Descreveu-se o caso de um paciente submetido à ressecção de um tumor no lobo temporal esquerdo, no giro de Wernicke, com sinais clínicos de via aérea difícil. Foi utilizada a técnica "dormindo-acordado-dormindo", com infusão contínua de propofol e remifentanil. A via aérea foi mantida com o uso da máscara laríngea, por abordagem lateral. CONCLUSÕES: A técnica utilizada foi eficaz para a obtenção de um paciente acordado e cooperativo no intra-operatório, tendo sido assegurada permeabilidade da via aérea com o uso da máscara laríngea. A inserção desse dispositivo por abordagem lateral é de especial interesse por se tratar de um paciente com possível dificuldade de acesso à via aérea, em procedimento cirúrgico em que era necessário evitar deslocamento do paciente e contaminação do campo cirúrgico.


BACKGROUND AND OBJECTIVES: During an awake craniotomy in which the Aachen Aphasia test is performed, it is necessary to use the "asleep-awake-asleep" anesthetic technique. The objective of this case report was to describe the anesthetic technique used in a patient with signs of difficult airway. CASE REPORT: The case of a patient who underwent resection of a tumor in the left temporal lobe, in the Wernicke gyrus, with clinical signs of difficult airway is reported. The "asleep-awake-asleep" anesthetic technique, with continuous infusion of propofol and remifentanil, was used. A laryngeal mask, inserted by the lateral approach, was used to keep the airways patency. CONCLUSIONS: The technique used was effective in obtaining an intraoperative awake and cooperative patient, and the airways were maintained patent with a laryngeal mask. Insertion of this device by the lateral approach is especially interesting since this was a patient who presented difficult airway and underwent a surgical procedure in which in which the patient must remain immobile and the surgical field cannot be contaminated.


JUSTIFICATIVA Y OBJETIVOS: Durante una craniotomía en que se realiza la prueba de Afasia de Aachen con el paciente despierto y cooperativo, se necesita el uso de la técnica anestésica "durmiendo-despierto-durmiendo". El objetivo de este relato de caso fue el de describir la técnica anestésica utilizada en paciente con señales de vía aérea difícil. RELATO DEL CASO: Se ha descrito el caso de un paciente sometido a la resección de un tumor en el lobo temporal izquierdo, en el giro de Wernicke, con señales clínicos de vía aérea difícil. Fue utilizada la técnica "durmiendo-despierto-durmiendo", con infusión continua de propofol y remifentanil. La vía aérea se mantuvo con el uso de la máscara laríngea, a través de abordaje lateral. CONCLUSIONES: La técnica utilizada fue eficaz para la obtención de un paciente despierto y cooperativo en el intraoperatorio, habiendo sido asegurada la permeabilidad de la vía aérea con el uso de la máscara laríngea. La inserción de ese dispositivo a través del abordaje lateral es de especial interés por tratarse de un paciente con una posible dificultad de acceso a la vía aérea, en procedimiento quirúrgico en que era necesario evitar desplazamiento del paciente y contaminación del campo quirúrgico.


Subject(s)
Humans , Male , Middle Aged , Craniotomy , Laryngeal Masks , Patient Compliance , Propofol
18.
Rev Bras Anestesiol ; 56(6): 654-7, 2006 Dec.
Article in Portuguese | MEDLINE | ID: mdl-19468610

ABSTRACT

BACKGROUND AND OBJECTIVES: During an awake craniotomy in which the Aachen Aphasia test is performed, it is necessary to use the 'asleep-awake-asleep' anesthetic technique. The objective of this case report was to describe the anesthetic technique used in a patient with signs of difficult airway. CASE REPORT: The case of a patient who underwent resection of a tumor in the left temporal lobe, in the Wernicke gyrus, with clinical signs of difficult airway is reported. The 'asleep-awake-asleep' anesthetic technique, with continuous infusion of propofol and remifentanil, was used. A laryngeal mask, inserted by the lateral approach, was used to keep the airways patency. CONCLUSIONS: The technique used was effective in obtaining an intraoperative awake and cooperative patient, and the airways were maintained patent with a laryngeal mask. Insertion of this device by the lateral approach is especially interesting since this was a patient who presented difficult airway and underwent a surgical procedure in which in which the patient must remain immobile and the surgical field cannot be contaminated.

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