Low Dose of BPA Induces Liver Injury through Oxidative Stress, Inflammation and Apoptosis in Long-Evans Lactating Rats and Its Perinatal Effect on Female PND6 Offspring.

Bisphenol A (BPA) is a phenolic compound used in plastics elaboration for food protection or packaging. BPA-monomers can be released into the food chain, resulting in continuous and ubiquitous low-dose human exposure. This exposure during prenatal development is especially critical and could lead to alterations in ontogeny of tissues increasing the risk of developing diseases in adulthood. The aim was to evaluate whether BPA administration (0.036 mg/kg b.w./day and 3.42 mg/kg b.w./day) to pregnant rats could induce liver injury by generating oxidative stress, inflammation and apoptosis, and whether these effects may be observed in female postnatal day-6 (PND6) offspring. Antioxidant enzymes (CAT, SOD, GR, GPx and GST), glutathione system (GSH/GSSG) and lipid-DNA damage markers (MDA, LPO, NO, 8-OHdG) were measured using colorimetric methods. Inducers of oxidative stress (HO-1d, iNOS, eNOS), inflammation (IL-1ß) and apoptosis (AIF, BAX, Bcl-2 and BCL-XL) were measured by qRT-PCR and Western blotting in liver of lactating dams and offspring. Hepatic serum markers and histology were performed. Low dose of BPA caused liver injury in lactating dams and had a perinatal effect in female PND6 offspring by increasing oxidative stress levels, triggering an inflammatory response and apoptosis pathways in the organ responsible for detoxification of this endocrine disruptor.

Activation of NLRP3 Inflammasome in Liver of Long Evans Lactating Rats and Its Perinatal Effects in the Offspring after Bisphenol F Exposure.

The liver is the organ responsible for the metabolism and detoxification of BPF, the BPA analogue that is replacing it in plastic-based products. It is not known whether BPF can trigger inflammatory responses via the NLRP3 inflammasome, which plays a major role in the development of liver disease. The aim of this study was to evaluate nitrosative stress species (RNS) and NLRP3 inflammasome activation in the liver of lactating dams after BPF exposure. Moreover, it was studied whether this effect could also be observed in the liver of female and male offspring at postnatal day 6 (PND6). 36 Long Evans rats were randomly distributed according to oral treatment into three groups: Control, BPF-low dose (LBPF; 0.0365 mg/kg b.w./day) group and BPF-high dose (HBPF; 3.65 mg/kg b.w./day) group. The levels of nitrosative stress-inducing proteins (eNOS, iNOS, HO-1d), NLRP3 inflammasome components (NLRP3, PyCARD, CASP1) and proinflammatory cytokines (IL-1ß, IL-18, IFN-γ and TNF-α) were measured by gene and protein expression in the liver of lactating dams and in female and male PND6 offspring. Lactating dams treated with LBPF showed a significant increase in iNOS and HO-1d, activation of NLRP3 components (NLRP3, PyCARD, CASP1) and promoted the release of proinflammatory cytokines such as IL-1ß, IL-18, IFN-γ and TNF-α. Similar effects were found in female and male PND6 offspring after perinatal exposure. LBPF oral administration and perinatal exposure caused an increase of nitrosative stress markers and proinflammatory cytokines. Also, NLRP3 inflammasome activation was significantly increased in in the liver of lactating dams and PND6 offspring.

Effects of GH on the Aging Process in Several Organs: Mechanisms of Action.

In order to investigate the possible beneficial effects of GH administration on the aging process, 24-month-old rats of both sexes and 10-month-old SAMP8 mice were used. Male rats showed increased fat content and decreased lean body mass together with enhanced vasoconstriction and reduced vasodilation of their aortic rings compared to young adult animals. Chronic GH treatment for 10 weeks increased lean body mass and reduced fat weight together with inducing an enhancement of the vasodilatory response by increasing eNOS and a reduction of the constrictory responses. Old SAMP8 male mice also showed insulin resistance together with a decrease in insulin production by the endocrine pancreas and a reduced expression of differentiation parameters. GH treatment decreased plasma levels and increased pancreatic production of insulin and restored differentiation parameters in these animals. Ovariectomy plus low calcium diet in rabbits induced osteoporosis Titanium implants inserted into these rabbit tibiae showed after one month lesser bone to implant (BIC) surface and bone mineral density (BMD). Local application of GH in the surgical opening was able to increase BIC in the osteoporotic group. The hippocampus of old rats showed a reduction in the number of neurons and also in neurogenesis compared to young ones, together with an increase of caspases and a reduction of Bcl-2. GH treatment was able to enhance significantly only the total number of neurons. In conclusion, GH treatment was able to show beneficial effects in old animals on all the different organs and metabolic functions studied.

Protective effects of 17-ß-oestradiol and phytoestrogen on age-induced oxidative stress and inhibition of surfactant synthesis in rat type II pneumocytes.

Epidemiological data suggest protective effects of oestrogen and phytoestrogen on lung tissue. This study aimed to elucidate the role of 17-ß-oestradiol and phytoestrogen in age-related inhibition of surfactant synthesis and oxidative stress in rat type II pneumocytes. Forty male and 66 female Wistar rats were used. Female rats were randomly kept intact or ovariectomized at age 12 months. At age 22 months, ovariectomized rats received 17-ß-oestradiol, soy extract, or no treatment. Oxidative stress markers CO, NO, cGMP and lipid peroxide (LPO), antioxidant enzymes and phosphatidylcholine (PC) were measured in cultured type II pneumocytes isolated at ages 2, 14, 18, 22 and 24 months. Old, male and ovariectomized rats showed significantly higher CO, NO, cGMP and LPO and lower PC content and antioxidant enzymes. 17-ß-oestradiol and phytoestrogen significantly reversed these effects. In conclusion, aging and oestrogen deprivation decreased PC synthesis and altered the redox status in type II pneumocytes, which were partially restored by 17-ß-oestradiol or soy supplementation.

The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity.

Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.

Social environment improves immune function and redox state in several organs from prematurely aging female mice and increases their lifespan.

Aging is associated with a chronic oxidative stress (increase of oxidants and decrease of antioxidants), which contributes to immunosenescence and therefore shorter longevity. Nevertheless, a positive social network has been related to the adequate maintenance of health and deceleration of aging. Adult prematurely aging mice (PAM) are characterized by their inadequate stress response to a T-maze, showing premature immunosenescence and oxidative stress establishment. These impairments contribute to shorter life spans in comparison to exceptional non-PAM (ENPAM). However, it is not known whether these characteristics of PAM could be prevented by a positive cohabitation. Therefore, the aim of the present work was to determine if the premature immunosenescence and oxidative stress shown by PAM could be avoided by the cohabitation with ENPAM, increasing their life span. Female CD1 PAM and ENPAM were divided into three experimental groups: PAM controls, ENPAM controls and a social environment experimental group, containing in the same cage ENPAM and PAM (proportion 5/2, respectively). After 2 months, mice were sacrificed and spleen, thymus, liver and heart removed. Later, several immune functions as well as oxidative stress parameters were assessed in spleen and thymus leukocytes. Also, several oxidative stress parameters were analyzed in liver and heart. The results showed that PAM, after co-housing with ENPAM, had improved immune functions and redox balance in spleen and thymus leukocytes. This improvement of redox state was also observed in liver and heart. Furthermore, all these positive effects seem to be related to the increased life span of PAM.

Xanthohumol exerts protective effects in liver alterations associated with aging.

BACKGROUND AND AIMS: Aging is associated with a deregulation of biological systems that lead to an increase in oxidative stress, inflammation, and apoptosis, among other effects. Xanthohumol is the main preylated chalcone present in hops (Humulus lupulus L.) whose antioxidant, anti-inflammatory and chemopreventive properties have been shown in recent years. In the present study, the possible protective effects of xanthohumol on liver alterations associated with aging were evaluated. METHODS: Male young and old senescence-accelerated prone mice (SAMP8), aged 2 and 10 months, respectively, were divided into four groups: non-treated young, non-treated old, old treated with 1 mg/kg/day xanthohumol, and old treated with 5 mg/kg/day xanthohumol. Male senescence-accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed and livers were collected. mRNA (AIF, BAD, BAX, Bcl-2, eNOS, HO-1, IL-1ß, NF-κB2, PCNA, sirtuin 1 and TNF-α) and protein expressions (BAD, BAX, AIF, caspase-3, Blc-2, eNOS, iNOS, TNF-α, IL1ß, NF-κB2, and IL10) were measured by RT-PCR and Western blotting, respectively. Mean values were analyzed using ANOVA. RESULTS: A significant increase in mRNA and protein levels of oxidative stress, pro-inflammatory and proliferative markers, as well as pro-apoptotic parameters was shown in old non-treated SAMP8 mice compared to the young SAMP8 group and SAMR1 mice. In general, age-related oxidative stress, inflammation and apoptosis were significantly decreased (p < 0.05) after XN treatment. In most cases, this effect was dose-dependent. CONCLUSIONS: XN was shown to modulate inflammation, apoptosis, and oxidative stress in aged livers, exerting a protective effect in hepatic alterations.

Comparison of the Effect of Melatonin Treatment before and after Brain Ischemic Injury in the Inflammatory and Apoptotic Response in Aged Rats.

Aging is associated with an increase in stroke risk. Melatonin, a potent free radical scavenger and broad spectrum antioxidant, has been shown to counteract inflammation and apoptosis in brain injury. However, little is known on the possible protective effects of melatonin in aged individuals affected by brain ischemia. Also, using melatonin before or after an ischemic stroke may result in significantly different molecular outcomes. The objective of the present study was to compare the effects of pre-ischemia vs. post-ischemia melatonin administration in an ischemic lesion in the cortex and hippocampus of senescent Wistar rats. An obstruction of the middle cerebral artery (MCA) to 18-month-old animals was performed. In general, animals treated with melatonin from 24 h prior to surgery until 7 days after the surgical procedure (PrevT) experienced a significant decrease in the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), glial fibrillary acidic protein (GFAP), Bcl-2-associated death promoter (BAD), and Bcl-2-associated X protein (BAX) in both cortex and hippocampus, while hippocampal levels of sirtuin 1 (SIRT1) and B-cell lymphoma 2 (Bcl-2) increased. Treatment of animals with melatonin only after surgery (AT) resulted in similar effects, but to a lesser extent than in the PrevT group. In any case, melatonin acted as a valuable therapeutic agent protecting aged animals from the harmful effects of cerebral infarction.

Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin.

The connection between the innate immune system, clock genes, and mitochondrial bioenergetics was analyzed during aging and sepsis in mouse heart. Our results suggest that the sole NF-κB activation does not explain the inflammatory process underlying aging; the former also triggers the NLRP3 inflammasome that enhances caspase-1-dependent maturation of IL-1ß. In this way, aged mice enter into a vicious cycle as IL-1ß further activates the NF-κB/NLRP3 inflammasome link. The origin of NF-κB activation was related to the age-dependent Bmal1/Clock/RORα/Rev-Erbα loop disruption, which lowers NAD(+) levels, reducing the SIRT1 deacetylase ability to inactivate NF-κB. Consequently, NF-κB binding to DNA increases, raising the formation of proinflammatory mediators and inducing mitochondrial impairment. The cycle is then closed with the subsequent NLRP3 inflammasome activation. This paired contribution of the innate immune pathways serves as a catalyst to magnify the response to sepsis in aged compared with young mice. Melatonin administration blunted the septic response, reducing inflammation and oxidative stress, and enhancing mitochondrial function at the levels of nonseptic aged mice, but it did not counteract the age-related inflammation. Together, our results suggest that, although with different strengths, chronoinflammaging constitutes the biochemical substrate of aging and sepsis, and identifies the NLRP3 inflammasome as a new molecular target for melatonin, providing a rationale for its use in NLRP3-dependent diseases.

Protective Actions of Cannabidiol on Aging-Related Inflammation, Oxidative Stress and Apoptosis Alterations in Liver and Lung of Long Evans Rats.

BACKGROUND: Aging is characterised by the progressive accumulation of oxidative damage which leads to inflammation and apoptosis in cells. This affects all tissues in the body causing the deterioration of several organs. Previous studies observed that cannabidiol (CBD) could extend lifespan and health span by its antioxidant, anti-inflammatory and autophagy properties. However, research on the anti-aging effect of CBD is still in the beginning stages. This study aimed to investigate the role of cannabidiol (CBD) in the prevention of age-related alterations in liver and lung using a murine model. METHODS: 15-month-old Long Evans rats were treated with 10 mg/kg b.w./day of CBD for 10 weeks and compared to animals of the same age as old control and 2-month-old animals as young control. Gene and/or protein expressions, by RT-qPCR and Western blotting, respectively, were assessed in terms of molecules related to oxidative stress (GST, GPx, GR and HO-1d), inflammation (NFκB, IL-1ß and TNF-α) and apoptosis (BAX, Bcl-2, AIF, and CASP-1). In addition, MDA and MPO levels were measured by colorimetric assay. Results were analysed by ANOVA followed by Tukey-Kramer test, considering statistically significant a p < 0.05. RESULTS: GST, GPx and GR expressions were significantly reduced (p < 0.01) in liver samples from old animals compared to young ones and CBD treatment was able to revert it. A significant increase was observed in old animals compared to young ones in relation to oxidative stress markers (MDA and HO-1d), proinflammatory molecules (NFκB, IL-1ß and TNF-α), MPO levels and proapoptotic molecules (BAX, AIF and CASP-1), while no significant alterations were observed in the antiapoptotic molecules (Bcl-2). All these changes were more noticeable in the liver, while the lung seemed to be less affected. In almost all the measured parameters, CBD treatment was able to revert the alterations caused by age restoring the levels to those observed in the group of young animals. CONCLUSIONS: Chronic treatment with CBD in 15-month-old rats showed beneficial effects in lung and more significantly in liver by reducing the levels of inflammatory, oxidative and apoptotic mediators, and hence the cell damage associated with these three processes inherent to aging.

Age-related differences in hepatic ischemia/reperfusion: gene activation, liver injury, and protective effect of melatonin.

BACKGROUND: Ischemia/reperfusion (I/R) causes functional and structural damage to liver cells, this being more pronounced with increasing age of the tissue. Melatonin is a pineal indole that has been shown to play an important role as a free radical scavenger and anti-inflammatory molecule. MATERIAL AND METHODS: The age-dependent responses to I/R were compared in 2-mo-old and 14-mo-old male Wistar rats. After 35 min of hepatic ischemia followed by 36 h of reperfusion, rats were sacrificed. Sham-operated control rats underwent the same protocol without real vascular occlusion. Animals were intraperitoneally injected with 10 mg/kg melatonin 24 h before the operation, at the time of surgery, and 12 and 24 h after it. The tissues were submitted to histopathologic evaluation. The levels of ALT and AST were analyzed in plasma. The expression of TNF-α, IL-1ß, IL-10, MCP-1, IFN-γ, iNOS, eNOS, Bad, Bax, Bcl2, AIF, PCNA, and NFKB1 genes were detected by RT-PCR in hepatic tissue. RESULTS: I/R was associated with significant increases in the expression of pro-inflammatory and pro-apoptotic genes in liver. Older rats submitted to I/R were found to respond with increased liver damage as compared with young rats, with serum ALT and AST levels significantly higher than in young animals. Mature rats also showed more evident increases in expression of pro-inflammatory cytokines (IL-1ß, MCP-1, and IFN-γ) as well as a decrease in the mRNA expression of IL-10 as compared with young animals. Pro-apoptotic genes (Bax, Bad, and AIF) were significantly enhanced in liver after I/R, without differences between young and mature animals. However, the expression of Bcl2 gene did not show any change. Melatonin treatment was able to lower the expression of pro-inflammatory cytokines and pro-apoptotic genes and to improve liver function, as indicated by normalization of plasma AST and ALT levels and by reduction of necrosis and microsteatosis areas. CONCLUSIONS: Melatonin treatment was able to reduce the I/R-stimulated pro-inflammatory and pro-apoptotic genes in the rat liver. Since older animals showed a more marked increase in inflammation and in liver injury, the treatment was more effective in those subjects.

Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases.

The concept of "aging" is defined as the set of gradual and progressive changes in an organism that leads to an increased risk of weakness, disease, and death. This process may occur at the cellular and organ level, as well as in the entire organism of any living being. During aging, there is a decrease in biological functions and in the ability to adapt to metabolic stress. General effects of aging include mitochondrial, cellular, and organic dysfunction, immune impairment or inflammaging, oxidative stress, cognitive and cardiovascular alterations, among others. Therefore, one of the main harmful consequences of aging is the development and progression of multiple diseases related to these processes, especially at the cardiovascular and central nervous system levels. Both cardiovascular and neurodegenerative pathologies are highly disabling and, in many cases, lethal. In this context, melatonin, an endogenous compound naturally synthesized not only by the pineal gland but also by many cell types, may have a key role in the modulation of multiple mechanisms associated with aging. Additionally, this indoleamine is also a therapeutic agent, which may be administered exogenously with a high degree of safety. For this reason, melatonin could become an attractive and low-cost alternative for slowing the processes of aging and its associated diseases, including cardiovascular and neurodegenerative disorders.

Free [NADH]/[NAD(+)] regulates sirtuin expression.

Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[NAD(+)] ratio, which is a major sensor for metabolite availability conserved from invertebrates to vertebrates.

Melatonin, and to a lesser extent growth hormone, restores colonic smooth muscle physiology in old rats.

There is increasing evidence that aging is associated with oxidative damage, inflammation, and apoptosis in different cell types. However, there is limited information regarding aging mechanisms in colon smooth muscle. Old male Wistar rats (22 months) were treated for 10 wks with melatonin or growth hormone (GH). Animals were sacrificed at 24 months of age by decapitation. The colon was dissected and the smooth muscle homogenized. H(2)O(2) and malonyl dialdehyde (MDA) content and catalase and glutathione peroxidase (GPX) activities were determined using colorimetric kits. Expression of nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX-2), caspase-3, and caspase-9 were determined by Western blot. Aging of colon smooth muscle correlated with an increase in H(2)O(2) and MDA levels when compared with young animals in both proximal and distal segments; these changes were associated with a decrease in the catalase activity in the distal colon. Oxidative stress correlated with an increase in COX-2 and NF-κB expression, which were accompanied by an enhanced expression of the pro-apoptotic enzyme caspase-3 and its upstream enzyme, caspase-9. Melatonin treatment normalized the oxidative, inflammatory, and apoptotic patterns, whereas GH replacement, although effective in reducing oxidative stress in distal colon, did not reverse the age-related inflammation or apoptosis. These results suggest that melatonin should be the treatment of choice to most effectively recover physiological functions in aged colonic smooth muscle.

Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences.

Endocrine disrupting chemicals (EDCs) can impair hippocampus-dependent behaviors in rat offspring and in children. In search for key processes underlying this effect, we compared the transcriptomes of rat hippocampus on postnatal day 6 after gestational and lactational exposure to three different EDCs at doses known to impair development of learning and memory. Aroclor 1254, a commercial PCB mixture (5 mg/kg or 0.5 mg/kg), or bisphenol A (5 mg/kg or 0.5 mg/kg) were administered in chow, chlorpyrifos (3 mg/kg or 1 mg/kg) was injected subcutaneously. Male hippocampus exhibited a common effect of all three chemicals on genes involved in cell-autonomous processes, Sox6, Sox11, Pou2f2/Oct2, and Pou3f2/Brn2, all upregulated at the high dose. Additional genes of the Sox and Pou families were affected by only one or two of the chemicals. Real time RT PCR showed a comparable expression change for bisphenol A also at the lower dose. Female hippocampus exhibited much fewer genes with expression changes (almost none with false discovery rate <0.05), and none of the genes of the Sox and Pou families was affected. Since gene network analyses in male hippocampus suggested a link between Sox6 and miR-24, known to be repressed by activation of ER-alpha and to repress Sox6 in other tissues, this microRNA was measured. miR-24 was downregulated by all chemicals at the high dose in males. Values of Sox6 mRNA and miR-24 were inversely correlated in individual male hippocampus samples, supporting the hypothesis that the change in Sox6 expression resulted from an action of miR-24. In contrast, miR-24 levels remained unchanged in hippocampus of females. A sexually dimorphic response of miR-24 may thus be at the basis of the sex difference in Sox6 expression changes following exposure to the three chemicals. ER-alpha expression was also sex-dependent, but the expression changes did not parallel those of potential downstream genes such as Sox6. Sox6 is known to suppress differentiation of Parvalbumin (Pvalb)-expressing interneurons. Individual Sox6 levels (FPKM) were inversely correlated with levels of Pvalb, but not with markers of Sox6-independent interneuron subpopulations, Nos1 and 5HT3aR. Effects on interneuron development are further suggested, in males, by expression changes of Nrg1 and its receptor Erbb4, controlling interneuron migration. Our study disclosed new types of EDC-responsive morphogenetic genes, and illustrated the potential relevance of microRNAs in sexually dimorphic EDC actions.

Growth Hormone As Antiaging Factor in Old Bones.

Aging induces changes in bone. Growth hormone (GH) is reduced by aging, and age-related changes observed in old bones might be due to a decrease in the GH/insulin-like growth factor-I (IGF-I) axis. GH administration on aged individuals is controversial. This study aimed to assess the effect of systemic GH treatment on bone properties, bone metabolism, and bone mineral density (BMD) in long bone of old rats. Aged Wistar rats were treated with GH at a dose of 2 mg/kg/day during 10 weeks. Plasma osteocalcin, IGF-I, and carboxy-terminal telopeptide of type I collagen levels were measured. Cross-sectional bone areas and BMD were measured by morphometric and densitometric analysis, respectively. Femora were analyzed by three point-bending testing. t-Test was used for statistical evaluation. p < 0.05 was considered to be significant. Significantly enhanced bone area, at the expense of the cortical area, was found in treated rats. The densitometric analysis showed 11% higher BMD in the experimental group. Significantly higher bone flexural modulus, stiffness, and ultimate load were observed in the treated rats. Plasma osteocalcin and IGF-I levels were significantly increased in the treated group, while the resorption marker concentration remained unchanged. Within the limitations of this experimental study, systemic GH administration has shown to enhance biomechanical properties, BMD, cortical mass, and plasma IGF-I and osteocalcin in old treated rats, compared to the control group; consequently, GH could be considered as an alternative therapy against age-related changes in the bone.

Does Clinical Photography Influence Satisfaction With Surgery in Adult Patients Operated on for Spinal Deformity?

BACKGROUND: Recently published data suggest that showing patients operated on for adolescent idiopathic scoliosis or kyphosis their preoperative and postoperative photographs may enhance their satisfaction and self-image as measured by Scoliosis Research Society Health-Related Quality of Life Questionnaire (SRS-22) scores. No data exist for adult spinal deformity (ASD) surgery. The aim of this study is to determine the effect on patient postoperative satisfaction and self-image of showing adult deformity patients their preoperative and postoperative whole body photographs. METHODS: This was a nonconcurrent prospective study. Patients operated on for ASD with a minimum 2-year postoperative follow-up who had preoperative full-body photographs taken by a professional photographer were included. Two follow-up visits were arranged 7 days apart. In the first visit, patients completed the SRS-22 questionnaire, and full-body standing photographs were taken. In the second visit, patients were asked to complete again questions 4, 6, 10, 14, 19 (self-image), 21, and 22 (satisfaction) of the SRS-22 after seeing their preoperative and postoperative full-body photographs. RESULTS: Thirty patients (28 female) were included. The median age at surgery was 50 years (26-76). The median follow-up was 51 months (24-120). SRS-22 results at first visit were: activity 2.79 ± 0.75; self-image 2.71 ± 0.82; pain 2.53 ± 1.10; mental health 3.08 ± 0.77; satisfaction 3.46 ± 1.20; global 2.74 ± 0.72. SRS22 results at second visit were: self-image 2.9 ± 0.75; satisfaction 4.02 ± 0.97. After seeing the preoperative and final follow-up photographs, patients experienced an improvement in SRS-22 self-image (P = .000) and satisfaction domains (P = .011). CONCLUSIONS: In patients operated on for ASD, showing preoperative and postoperative photographs improves patient satisfaction with surgery and self-image. LEVEL OF EVIDENCE: 3. CLINICAL RELEVANCE: Our results could be a starting point for introducing full-body clinical photographs as a routine clinical tool in adult deformity patients undergoing surgery.

Photographic sagittal plane analysis and its clinical correlation after surgery for adult spinal deformity: a preliminary study.

PURPOSE: The aim of this study is to determine the correlation between photographic sagittal parameters and patient-reported outcome measures (PROM) results in adult patients operated on spinal deformity. METHODS: Non-concurrent prospective study. INCLUSION CRITERIA: age at surgery older than 25, minimum 2-year follow-up after a 5 or more level fusion for adult spinal deformity (ASD). Full body lateral standing photographs were taken with adhesive markers placed on ten bony landmarks. SRS-22 and SF-36 questionnaires were completed for every patient. The following photographic parameters were measured: lumbar angle, lumbar curve, thoracic inclination (TI), trunk angle, pelvic tilt, head angle, neck angle, cervicothoracic angle, lumbar vector angle (LVA), dorsal vector angle (DVA), cervical vector angle (CVA), cranial pelvic angle (CrPA), cranial sacral angle (CrSA), fibular inclination angle (FIA) and cranial sagittal vertical axis measured to sacrum (Cr-S), greater trochanter (Cr-GT), knee (Cr-K) and ankle (Cr-A). RESULTS: 65 patients (58 female) operated on ASD in a single institution were included. Age at surgery was 61 years (26-67). Postoperative follow-up was 53 months (24-120). Spearman rank order test showed several significant (p ≤ 0.01) correlations. After multivariate linear regression analysis age, LVA and TI remained as predictors for SRS image scores (corrected r2 0.41), LVA for SRS satisfaction (corrected r2 0.27), CrPA and age for SRS total scores (corrected r2 0.33), FIA and age for SF36 physical functioning (corrected r2 0.36) and CrSA for SF36 role physical (corrected r2 0.14). CONCLUSIONS: Some sagittal photographic parameters may predict mid-term clinical results after ASD surgery.

Is the Cranial Sagittal Vertical Axis (Cr-SVA) a Better Midterm Predictor of Clinical Results Than C7-SVA in Adult Patients Operated on Spinal Deformity After a Minimum 2-Year Follow-Up?

STUDY DESIGN: This is nonconcurrent prospective study approved by the Institutional Research Ethics Committee. OBJECTIVE: The purpose of this study is to determine if the cranial sagittal vertical axis (Cr-SVA) measured in full spine standing radiographs is a better predictor of clinical results than the C7 sagittal vertical axis (C7-SVA) in adult patients operated on spinal deformity with a minimum 2-year follow-up after surgery. SUMMARY OF BACKGROUND DATA: The Cr-SVA has recently been described as a better predictor of health-related quality of life outcomes than the C7-SVA for patients with adult spinal deformity (ASD) before undergoing surgery. This has not been confirmed in patients after ASD surgery. METHODS: Inclusion criteria were age at surgery more than 25 years and a minimum 2-year follow-up after a ≥5 level fusion for ASD. Full-length standing lateral radiographs (including nasion-inion line, spine, and femoral heads) and Scoliosis Research Society 22 Questionnaire and SF36 questionnaires were available for every patient at the final follow-up. The distance from the Cr-SVA to the posterior corner of S1 (Cr-SVA-S) and to the centers of the hip (Cr-SVA-H) was measured and also the C7-SVA, lumbar lordosis, pelvic incidence, pelvic tilt, and PI-LL. RESULTS: Sixty-five patients (58 female individuals) operated on ASD in a single institution were included. Age at surgery was 61 years (26-67). The mean follow-up was 53 months (24-120). Spearman rank-order test showed several significant correlations. After multivariable analysis, only Cr-SVA-S and age persisted as predictors for Scoliosis Research Society (SRS) image scores, Cr-SVA-H for SRS satisfaction, Cr-SVA-H and age for SRS total scores, Cr-SVA-H and age for SF36 Physical Function, Cr-SVA-S for SF36 Role Physical, Cr-SVA-H for SF36 Bodily Pain, and Cr-SVA-H for SF36 Role Emotional. CONCLUSIONS: The Cr-SVA measured in full spine standing radiographs seems to be a better predictor of health-related quality of life outcomes than the C7-SVA for adults operated on spinal deformity >2 years after surgery.

Tempol protects the gallbladder against ischemia/reperfusion.

Impairment in gallbladder emptying, increase in residual volume, and reduced smooth muscle contractility are hallmarks of acute acalculous cholecystitis and seem to be related to ischemia/reperfusion (I/R). This study was designed to determine the effects of tempol, a general antioxidant, on I/R-induced changes in gallbladder contractile capacity, the mechanisms involved in the contractile process, and the level of inflammatory mediators. Experimental gallbladder I/R was induced in male guinea pigs by common bile duct ligation for 2 days, then a deligation of the duct was performed and after 2 days the animals were sacrificed. A group of animals was treated with tempol, administered in the drinking water at 1 mmol/l for 10 days prior the bile duct ligation and until animal sacrifice. Isometric tension recordings showed that KCl and cholecystokinin-induced contractions were impaired by I/R, which correlated with decreased F-actin content and detrimental effects on Ca(2+) influx. In addition, I/R depolarized mitochondrial membrane potential, as indicated by the reduction of the heterogeneity of the rhodamine123 fluorescence signal, and increased the expression of NF-kappaB, COX-2, and iNOS. Tempol treatment improved contractility via normalization of Ca(2+) handling and improvement of F-actin content. Moreover, the antioxidant ameliorated mitochondrial polarity and normalized the expression levels of the inflammatory mediators. These results show that antioxidant treatment protects the gallbladder from I/R, indicating the potential therapeutic benefits of tempol in I/R injury.