Metabolic switching is impaired by aging and facilitated by ketosis independent of glycogen.

The ability to switch between glycolysis and ketosis promotes survival by enabling metabolism through fat oxidation during periods of fasting. Carbohydrate restriction or stress can also elicit metabolic switching. Keto-adapting from glycolysis is delayed in aged rats, but factors mediating this age-related impairment have not been identified. We measured metabolic switching between glycolysis and ketosis, as well as glycogen dynamics, in young and aged rats undergoing time-restricted feeding (TRF) with a standard diet or a low carbohydrate ketogenic diet (KD). TRF alone reversed markers of insulin-related metabolic deficits and accelerated metabolic switching in aged animals. A KD+TRF, however, provided additive benefits on these variables. Remarkably, the ability to keto-adapt was not related to glycogen levels and KD-fed rats showed an enhanced elevation in glucose following epinephrine administration. This study provides new insights into the mechanisms of keto-adaptation demonstrating the utility of dietary interventions to treat metabolic impairments across the lifespan.

Sex differences in age-related impairments vary across cognitive and physical assessments in rats.

Inclusion of female subjects in preclinical biomedical research is imperative for understanding mechanisms of age-related cognitive decline, as more than half of individuals older than 65 are female. In rodents, however, few behavioral and physical assessments have been conducted in both sexes within the same study. The current article documents data obtained from young and aged rats of both sexes that performed a battery of cognitive and physical assessments to examine for potential interactions between sex and age. Physical performance was measured with a rotarod test of motor coordination, assessment of maximum grip strength, and swim speed. While females outperformed males in rotarod and grip strength, there was also an age-dependent decline in physical performance in both sexes. Cognitive assessments included the Morris watermaze test of hippocampal dependent spatial memory and a biconditional association task with a working memory (WM) component, both of which were not significantly different across sex. Notably, a cognitive dual task that simultaneously tests working memory (WM) and biconditional association task (BAT) acquisition has previously been shown to be more sensitive to age-related cognitive decline than the watermaze in male rats, which is replicated here in both female and male rats. Furthermore, young and aged females (<27 months) spent a similar percent of time in each estrus cycle phase and phase did not influence WM/BAT performance. Future studies utilizing similar behavioral paradigms to examine the neurobiology of cognitive aging should be representative of the human population they intend to model through the inclusion of female subjects. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Age and Ketogenic Diet Have Dissociable Effects on Synapse-Related Gene Expression Between Hippocampal Subregions.

As the number of individuals living beyond the age of 65 is rapidly increasing, so is the need to develop strategies to combat the age-related cognitive decline that may threaten independent living. Although the link between altered neuronal signaling and age-related cognitive impairments is not completely understood, it is evident that declining cognitive abilities are at least partially due to synaptic dysfunction. Aging is accompanied by well-documented changes in both excitatory and inhibitory synaptic signaling across species. Age-related synaptic alterations are not uniform across the brain, however, with different regions showing unique patterns of vulnerability in advanced age. In the hippocampus, increased activity within the CA3 subregion has been observed across species, and this can be reversed with anti-epileptic medication. In contrast to CA3, the dentate gyrus shows reduced activity with age and declining metabolic activity. Ketogenic diets have been shown to decrease seizure incidence and severity in epilepsy, improve metabolic function in diabetes type II, and improve cognitive function in aged rats. This link between neuronal activity and metabolism suggests that metabolic interventions may be able to ameliorate synaptic signaling deficits accompanying advanced age. We therefore investigated the ability of a dietary regimen capable of inducing nutritional ketosis and improving cognition to alter synapse-related gene expression across the dentate gyrus, CA3 and CA1 subregions of the hippocampus. Following 12 weeks of a ketogenic or calorie-matched standard diet, RTq-PCR was used to quantify expression levels of excitatory and inhibitory synaptic signaling genes within CA1, CA3 and dentate gyrus. While there were no age or diet-related changes in CA1 gene expression, expression levels were significantly altered within CA3 by age and within the dentate gyrus by diet for several genes involved in presynaptic glutamate regulation and postsynaptic excitation and plasticity. These data demonstrate subregion-specific alterations in synaptic signaling with age and the potential for a ketogenic diet to alter these processes in dissociable ways across different brain structures that are uniquely vulnerable in older animals.

Lycopene mitigates pulmonary emphysema induced by cigarette smoke in a murine model.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by a non-fully reversible airflow limitation comprising chronic bronchitis and pulmonary emphysema both being induced by cigarette smoke (CS) exposure. Lycopene has shown antioxidant and anti-inflammatory properties that can prevent acute lung inflammation and emphysema. We hypothesized that administration with lycopene would repair lung damage in emphysema caused by CS exposure. Mice were administered with two different doses of lycopene (25 or 50 mg/kg/day, diluted in sunflower oil by orogastric gavage) and then exposed to 60 days of CS or not (CG). Lycopene promoted a reduction in the number of total leukocytes and it improved pulmonary emphysema. Lycopene was able to minimize redox processes by decreasing lipid peroxidation and DNA damage, and by having an increase in the activities of SOD, CAT and GSH content. Furthermore, it decreased levels of TNF-α, IFN-γ and IL-10. In addition, it was able to decrease MPO activity and nitrite content. In conclusion, our data elucidated the role of lycopene as an antioxidant and anti-inflammatory agent in mice exposed to CS.

A Ketogenic Diet Improves Cognition and Has Biochemical Effects in Prefrontal Cortex That Are Dissociable From Hippocampus.

Age-related cognitive decline has been linked to a diverse set of neurobiological mechanisms, including bidirectional changes in proteins critical for neuron function. Importantly, these alterations are not uniform across the brain. For example, the hippocampus (HPC) and prefrontal cortex (PFC) show distinct patterns of dysfunction in advanced age. Because higher cognitive functions require large-scale interactions across prefrontal cortical and hippocampal networks, selectively targeting an alteration within one region may not broadly restore function to improve cognition. One mechanism for decline that the PFC and HPC share, however, is a reduced ability to utilize glucose for energy metabolism. Although this suggests that therapeutic strategies bypassing the need for neuronal glycolysis may be beneficial for treating cognitive aging, this approach has not been empirically tested. Thus, the current study used a ketogenic diet (KD) as a global metabolic strategy for improving brain function in young and aged rats. After 12 weeks, rats were trained to perform a spatial alternation task through an asymmetrical maze, in which one arm was closed and the other was open. Both young and aged KD-fed rats showed resilience against the anxiogenic open arm, training to alternation criterion performance faster than control animals. Following alternation testing, rats were trained to perform a cognitive dual task that required working memory while simultaneously performing a bi-conditional association task (WM/BAT), which requires PFC-HPC interactions. All KD-fed rats also demonstrated improved performance on WM/BAT. At the completion of behavioral testing, tissue punches were collected from the PFC for biochemical analysis. KD-fed rats had biochemical alterations within PFC that were dissociable from previous results in the HPC. Specifically, MCT1 and MCT4, which transport ketone bodies, were significantly increased in KD-fed rats compared to controls. GLUT1, which transports glucose across the blood brain barrier, was decreased in KD-fed rats. Contrary to previous observations within the HPC, the vesicular glutamate transporter (VGLUT1) did not change with age or diet within the PFC. The vesicular GABA transporter (VGAT), however, was increased within PFC similar to HPC. These data suggest that KDs could be optimal for enhancing large-scale network function that is critical for higher cognition.

Taurine treatment decreases inflammation and oxidative stress in lungs of adult mice exposed to cigarette smoke.

Taurine is the major free amino acid found in mammalian cells and is known to be an antioxidant and membrane-stabilizing agent. This study aimed to evaluate the effects of taurine on oxidative stress and inflammatory response in the lungs of mice exposed to cigarette smoke. Fifty male C57BL/6 mice were divided into 5 groups: control group (CG), vehicle group (VG), taurine group (TG), cigarette smoke group (CSG), and cigarette smoke + taurine group (CSTG). For five consecutive days, CSG and CSTG were exposed to 4 cigarettes 3 times a day. Taurine administration was able to reduce total leukocytes in bronchoalveolar lavage fluid in CSTG compared to CSG. There was an increase in antioxidant superoxide dismutase and catalase activity in CSG compared to that in CG and TG, and a decrease in CSTG compared to CSG. There was an increase in the concentration of TNF and IL-17 in CSG and CSTG compared to CG and TG. There was an increase in the concentration of IL-22 in CSG compared to CG and TG, and a decrease in CSTG compared to CSG. The administration of taurine has been shown to reduce the inflammation and oxidative stress induced by short-term exposure to cigarette smoke.

Dissociable effects of advanced age on prefrontal cortical and medial temporal lobe ensemble activity.

The link between age-related cellular changes within brain regions and larger scale neuronal ensemble dynamics critical for cognition has not been fully elucidated. The present study measured neuron activity within medial prefrontal cortex (PFC), perirhinal cortex (PER), and hippocampal subregion CA1 of young and aged rats by labeling expression of the immediate-early gene Arc. The proportion of cells expressing Arc was quantified at baseline and after a behavior that requires these regions. In addition, PER and CA1 projection neurons to PFC were identified with retrograde labeling. Within CA1, no age-related differences in neuronal activity were observed in the entire neuron population or within CA1 pyramidal cells that project to PFC. Although behavior was comparable across age groups, behaviorally driven Arc expression was higher in the deep layers of both PER and PFC and lower in the superficial layers of these regions. Moreover, age-related changes in activity levels were most evident within PER cells that project to PFC. These data suggest that the PER-PFC circuit is particularly vulnerable in advanced age.

Impaired discrimination with intact crossmodal association in aged rats: A dissociation of perirhinal cortical-dependent behaviors.

The perirhinal cortex (PRC) supports associative memory and perception, and PRC dysfunction impairs animals' abilities to associate stimulus features across sensory modalities. PRC damage also leads to deficits in discriminating between stimuli that share features. Although PRC-dependent stimulus discrimination has been shown to be impaired with advanced age, data regarding the abilities of older adults and other animals to form PRC-dependent associations have been equivocal. Moreover, the extent to which similar neural computations within the PRC support associative memory versus discrimination abilities have not been directly examined. In the current study, young and aged rats were cross-characterized on two PRC-dependent crossmodal object recognition (CMOR) tasks to test associative memory, and a LEGO object discrimination task. In the CMOR tasks, rats were familiarized with an object with access to tactile input and then tested for recognition with visual input only. The relative exploration time of novel versus familiar objects indicated that aged rats showed preference for the novel over familiar object with and without an epoch of multimodal preexposure to the familiar object prior to the testing session. Furthermore, crossmodal recognition performance between young and aged rats was not significantly different. In contrast, for the LEGO object discrimination task, aged rats were impaired relative to young rats. Notably, aged rats that performed poorly on the LEGO object discrimination task had better performance on the CMOR tasks. The dissociation of discrimination and association abilities with age suggests that these behaviors rely on distinct neural computations within PRC-medial temporal lobe circuit. (PsycINFO Database Record

The Antiepileptic Ketogenic Diet Alters Hippocampal Transporter Levels and Reduces Adiposity in Aged Rats.

Nutritional ketosis is induced by high fat/low carbohydrate dietary regimens, which produce high levels of circulating ketone bodies, shifting metabolism away from glucose utilization. While ketogenic diets (KD) were initially introduced to suppress seizures, they are garnering attention for their potential to treat a myriad of neurodegenerative and metabolic disorders that are associated with advanced age. The feasibility and physiological impact of implementing a long-term KD in old animals, however, has not been systematically examined. In this study, young and aged rats consumed a calorically- and nutritionally-matched KD or control diet for 12 weeks. All KD-fed rats maintained higher levels of BHB and lower levels of glucose relative to controls. However, it took the aged rats longer to reach asymptotic levels of BHB compared to young animals. Moreover, KD-fed rats had significantly less visceral white and brown adipose tissue than controls without a loss of lean mass. Interestingly, the KD led to significant alterations in protein levels of hippocampal transporters for monocarboxylates, glucose, and vesicular glutamate and gamma-aminobutyric acid. Most notably, the age-related decline in vesicular glutamate transporter expression was reversed by the KD. These data demonstrate the feasibility and potential benefits of KDs for treating age-associated neural dysfunction.

The administration of surfactant decreased oxidative stress in lungs of mice exposed to cigarette smoke.

The alveolar surfactant, which composition consists of a unique and complex mixture of lipids and proteins, has immunomodulatory action. This study aimed to evaluate the effects of exogenous surfactant on pulmonary inflammatory response in mice exposed to cigarette smoke (CS). Twenty-four mice C57BL/6 were divided into four groups: control group exposed to ambient air (CG); surfactant treated group (SG); CS exposed group (CSG) and CS exposed group treated with surfactant (CSSG). For five days, CSG and CSSG were exposed to 12 commercial cigarettes/day and SG and CSSG received the surfactant by intranasal instillation. At the end of the experiment, the animals were euthanatized for the collection of bronchoalveolar lavage fluid (BALF) and lungs. The total number of leukocytes in BALF increased in CSG compared to CG, however, there was a decrease in CSSG compared to CSG. There was an increase in lipid peroxidation in SG and CSG compared to CG while there was a decrease in CSSG compared to CSG. Regarding the antioxidant enzymes, the catalase (CAT) activity increased in all groups compared to CG and the superoxide dismutase (SOD) activity decreased in CSG compared to the CG and SG. There was an increase in TNF in SG, CSG and CSSG compared to CG. There was an increase in IL-17 in CSSG compared to CG. There was an increase in CCL5 in SG and CSSG compared to CG. Therefore, our results demonstrated that the administration of exogenous surfactant was able to decrease the oxidative processes in the lungs of mice induced by short-term exposure to CS.

Extrapulmonary effects of temporal exposure to cigarette smoke.

This study aimed to evaluate the extrapulmonary effects of exposure to cigarette smoke (CS) through the analysis of blood components and histopathological examinations of the trachea and diaphragm muscle (DM) in C57BL/6 mice. Thirty-six animals were exposed to six cigarettes per day for 5 days. The mice were divided into a control group (CG) and groups exposed to CS for 1 (CS1D), 2 (CS2D), 3 (CS3D), 4 (CS4D), and 5 (CS5D) days. The trachea, DM, and blood were collected for morphometric and biochemical analyses. In comparison with the CG, CS4D and CS5D mice showed an increased influx of inflammatory cells into the DM and trachea. Increased glycogen deposits in the tracheal tissue of CS3D mice were observed, compared with that in CG, CS1D, and CS2D mice. In the blood serum, the number of inflammatory cells and the concentration of cholesterol increased in CS1D mice, compared with the CG. Alanine aminotransferase (ALT) levels were elevated in CS5D mice, compared with those in CS3D and CS4D mice. Aspartate aminotransferase (AST) levels were elevated in CS3D and CS5D mice, compared with those in the CG. Urea levels were significantly increased in CS5D mice, compared with CS1D mice. Our results showed extrapulmonary effects of short-term exposure to CS in adult mice.

The antioxidant and anti-inflammatory properties of lycopene in mice lungs exposed to cigarette smoke.

Lycopene is a carotenoid with known antioxidant and anti-inflammatory properties. We aimed to evaluate the in vitro and in vivo effects of lycopene on reducing the redox imbalance and inflammation induced by cigarette smoke (CS). For the in vitro study, J774A.1 (macrophages) cells were incubated in the presence of 0.5, 1.0, 2.0, 4.0, 8.0, 10.0 and 25 µM of lycopene for 3, 6 and 24 h or in the presence of 0.1%, 0.25%, 0.5%, 0.625%, 1.25%, 2.25%, 5% and 10% cigarette smoke extract (CSE) for 3, 6 and 24 h to assess cell viability and measurement of intracellular reactive oxygen species (ROS). For the in vivo study, 40 mice were divided into 5 groups: a control exposed to ambient air (CG), a vehicle-control group that received 200 µl of sunflower oil by orogastric gavage, a group exposed to CS and two groups administered lycopene (diluted in sunflower oil) at doses of either 25 or 50 mg/kg/day prior to exposure to CS (LY25+CS and LY50+CS). The total treatment time lasted 5 days. A cell viability decrease was observed at 10- and 25-µM concentrations of lycopene in 3, 6 and 24 h compared with CG. There was an increase of ROS production in 24 h in CS compared with CG. Lycopene concentrations of 1 µM and 2 µM were able to reduce the production of ROS in 24 h compared with CS. In the bronchoalveolar lavage fluid, the total number of leukocytes increased in the CS group compared with the control groups (CG). Administration with lycopene at the highest dose suppressed this CS-induced increase in leukocytes. Lipid peroxidation and DNA damage increased in the CS group compared with that in the controls, and this increase was suppressed by lycopene at the highest dose. In contrast, superoxide dismutase activity decreased in the CS group compared with that in the controls. Catalase activity also increased in the CS group compared with that in both control groups, and this increase was suppressed in LY25+CS and LY50+CS. There was an increase in the levels of tumor necrosis factor-α, interferon-γ and interleukin-10 after exposure to CS, and these effects were suppressed by both doses of lycopene. These data elucidate the role of lycopene as an antioxidant and anti-inflammatory agent in these two models of short-term exposure to CS.

The exposure to formaldehyde causes renal dysfunction, inflammation and redox imbalance in rats.

Twenty-eight Fischer male rats were divided into four groups: control group (CG), exposed to the ambient air, and groups exposed to formaldehyde (FA) at concentrations of 1% (FA1%), 5% (FA5%) and 10% (FA10%). Kidney function was assessed by dosage of uric acid, creatinine and urea. Morphometry was performed on the thickness of the lumen of Bowman's capsule and diameter of the lumen of the renal tubules. We evaluated the redox imbalance through the catalase and superoxide dismutase activity as well as oxidative damage by lipid peroxidation. Inflammatory chemokines CCL2, CCL3 and CCL5 were analyzed by enzyme immunoassays. There was an increase in the concentration of urea in FA10% compared with CG and FA1%. The levels of creatinine, renal lumen and lipid peroxidation increased in all FA-treated groups compared with CG. The concentration of uric acid in FA10% was lower compared with all other groups. There was an increase in the space of Bowman's capsule in FA5% and FA10% compared with CG and FA1%. However, the superoxide dismutase activity was higher in FA5% compared with other groups while CCL5 was higher in FA1% compared with CG. The exposure to formaldehyde in a short period of time leads to changes in the kidney function, inflammation and morphology, as well as promoted the increase of superoxide dismutase activity and oxidative damage.

The Effects of the Combination of a Refined Carbohydrate Diet and Exposure to Hyperoxia in Mice.

Obesity is a multifactorial disease with genetic, social, and environmental influences. This study aims at analyzing the effects of the combination of a refined carbohydrate diet and exposure to hyperoxia on the pulmonary oxidative and inflammatory response in mice. Twenty-four mice were divided into four groups: control group (CG), hyperoxia group (HG), refined carbohydrate diet group (RCDG), and refined carbohydrate diet + hyperoxia group (RCDHG). The experimental diet was composed of 10% sugar, 45% standard diet, and 45% sweet condensed milk. For 24 hours, the HG and RCDHG were exposed to hyperoxia and the CG and RCDG to ambient air. After the exposures were completed, the animals were euthanized, and blood, bronchoalveolar lavage fluid, and lungs were collected for analyses. The HG showed higher levels of interferon-γ in adipose tissue as compared to other groups and higher levels of interleukin-10 and tumor necrosis factor-α compared to the CG and RCDHG. SOD and CAT activities in the pulmonary parenchyma decreased in the RCDHG as compared to the CG. There was an increase of lipid peroxidation in the HG, RCDG, and RCDHG as compared to the CG. A refined carbohydrate diet combined with hyperoxia promoted inflammation and redox imbalance in adult mice.

Oxidative effects on lung inflammatory response in rats exposed to different concentrations of formaldehyde.

The formaldehyde (FA) is a crosslinking agent that reacts with cellular macromolecules such as proteins, nucleic acids and molecules with low molecular weight such as amino acids, and it has been linked to inflammatory processes and oxidative stress. This study aimed to analyze the oxidative effects on pulmonary inflammatory response in Fischer rats exposed to different concentrations of FA. Twenty-eight Fischer rats were divided into 4 groups (N = 7). The control group (CG) was exposed to ambient air and three groups were exposed to different concentrations of FA: 1% (FA1%), 5% (FA5%) and 10% (FA10%). In the Bronchoalveolar Lavage Fluid (BALF), the exposure to a concentration of 10% promoted the increase of inflammatory cells compared to CG. There was also an increase of macrophages and lymphocytes in FA10% and lymphocytes in FA5% compared to CG. The activity of NADPH oxidase in the blood had been higher in FA5% and FA10% compared to CG. The activity of superoxide dismutase enzyme (SOD) had an increase in FA5% and the activity of the catalase enzyme (CAT) showed an increase in FA1% compared to CG. As for the glutathione system, there was an increase in total glutathione (tGSH), reduced glutathione (GSH) and oxidized glutathione (GSSG) in FA5% compared to CG. The reduced/oxidized glutathione ratio (GSH/GSSG) had a decrease in FA5% compared to CG. There was an increase in lipid peroxidation compared to all groups and the protein carbonyl formation in FA10% compared to CG. We also observed an increase in CCL2 and CCL5 chemokines in the treatment groups compared to CG and in serum there was an increase in CCL2, CCL3 and CCL5 compared to CG. Our results point out to the potential of formaldehyde in promoting airway injury by increasing the inflammatory process as well as by the redox imbalance.

Long-term exposure to ultrasonically nebulized distilled water and saline causes cellular influx and oxidative stress in lung tissue of rats.

PURPOSE: The aim of this study was to evaluate of the effect of distilled water and saline ultrasonic nebulization on the inflammatory and oxidative stress responses and on the lower airway architecture. MATERIALS AND METHODS: Twenty-one male Fischer rats were distributed into 3 groups of 7 animals each: a control group (CG), exposed to ambient air; a saline group (SG), exposed to 0.9% sodium chloride (NaCl); and a group exposed to distilled water (DWG). The exposure was carried out in a box attached to an ultrasonic inhaler, occurring for 20 min, 3 times a day for 6 months. At 24h after the last exposure, the animals were euthanized. The bronchoalveolar lavage fluid (BALF) and lungs were collected for study. RESULTS: There was an increase of inflammatory cells in the pulmonary tissue BALF in the DWG compared with the CG. The DWG showed an increase of inflammatory cells compared with the SG and CG. The DWG and SG had higher NADPH oxidase activity than the CG. The volume density (Vv) of the alveolar septum was higher in the DWG than in the SG and CG, and the DWG also had a higher Vv of collagen fibers than the other 2 groups. The DWG presented elevated content of thiobarbituric acid reactive substances in lung homogenates relative to the SG and CG. CONCLUSIONS: The ultrasonic nebulization of distilled water increased the influx of inflammatory cells and oxidative damage, and promoted changes in the lung architecture.

Influence of sexual dimorphism on pulmonary inflammatory response in adult mice exposed to chloroform.

Chloroform is an organic solvent used as an intermediate in the synthesis of various fluorocarbons. Despite its widespread use in industry and agriculture, exposure to chloroform can cause illnesses such as cancer, especially in the liver and kidneys. The aim of the study was to analyze the effects of chloroform on redox imbalance and pulmonary inflammatory response in adult C57BL/6 mice. Forty animals were divided into 4 groups (N = 10): female (FCG) and male (MCG) controls, and females (FEG) and males (MEG) exposed to chloroform (7.0 ppm) 3 times/d for 20 minutes for 5 days. Total and differential cell counts, oxidative damage analysis, and protein carbonyl and antioxidant enzyme catalase (CAT) activity measurements were performed. Morphometric analyses included alveolar area (Aa) and volume density of alveolar septa (Vv) measurements. Compared to FCG and MCG, inflammatory cell influx, oxidative damage to lipids and proteins, and CAT activity were higher in FEG and MEG, respectively. Oxidative damage and enzyme CAT activity were higher in FEG than in FCG. The Aa was higher in FEG and MEG than in FCG and MCG, respectively. The Vv was lower in FEG and MEG than in FCG and MCG, respectively. This study highlights the risks of occupational chloroform exposure at low concentrations and the intensity of oxidative damage related to gender. The results validate a model of acute exposure that provides cellular and biochemical data through short-term exposure to chloroform.

Exposure to cigarette smoke during pregnancy causes redox imbalance and histological damage in lung tissue of neonatal mice.

Smoking during pregnancy is directly associated with numerous serious conditions, such as premature birth, low birth weight, and perinatal mortality. We quantitatively evaluated histological inflammatory alterations, oxidative damage by lipid peroxidation, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the lungs of mice exposed to cigarette smoke during pregnancy. Eight female and four male mice were mated for five days. Pregnant female mice were randomly allocated to the control group or to the cigarette smoke group (n = 8) in which they were exposed to 12 cigarettes per day in an exposure chamber, three times a day for 21 days. The control group (CG; n = 8) was kept in the exposure chamber for the same duration, but without exposure to cigarette smoke. Six newborn mice from both groups were weighed 24 hours after birth and then euthanized. Lung tissue was collected and subjected to histomorphometric and biochemical analyses. The cigarette smoke group showed a significant reduction in snout-vent length compared to the control group. Histomorphometric analysis indicated increased alveolar septal thickness and a larger alveolar lumen in mice exposed to cigarette smoke than in mice in the control group. We observed increased alveolar inflammatory infiltrate, decreased SOD activity, and significantly higher oxidative damage in the cigarette smoke group. Our data indicate that cigarette smoke exposure during pregnancy decreases body length at birth, changes lung tissue, and causes redox imbalance and histological damage in newborn mice.

Temporal analysis of oxidative effects on the pulmonary inflammatory response in mice exposed to cigarette smoke.

The most common factor related to the chronic obstructive pulmonary disease (COPD) development is the chronic smoking habit. Our study describes the temporal kinesis of pulmonary cellular influx through BALF analyses of mice acutely exposed to cigarette smoke (CS), the oxidative damage and antioxidative enzyme activities. Thirty-six mice (C57BL/6, 8weeks old, male) were divided in 6 groups: the control group (CG), exposed to ambient air, and the other 30 mice were exposed to CS. Mice exposed to CS presented, especially after the third day of exposure, different cellular subpopulations in BALF. The oxidative damage was significantly higher in CS exposed groups compared to CG. Our data showed that the evaluated inflammatory cells, observed after three days of CS exposure, indicate that this time point could be relevant to studies focusing on these cellular subpopulation activities and confirm the oxidative stress even in a short term CS exposure.

Total thyroidectomy for benign thyroid diseases.

OBJECTIVE: To review the indications for total thyroidectomy as the preferred option in certain benign diseases of the thyroid in order to prevent recurrence or future reoperations. METHODS: A retrospective study of patients with benign thyroid diseases, carried out from January 1997 to December 2009, analyzing the data relating to age, surgical treatment and postoperative evolution. RESULTS: The mean age was 51.8 years (21/77), with the highest incidence in the fifth and sixth decades of life, with 34 (51.5%) patients. The most common preoperative diagnosis was nontoxic multinodular goiter, of which seven were also intrathoracic, followed by autoimmune thyroiditis; recurrent goiter occurred in 11 cases. Multinodular goiter was found in 37 (56.1%) patients, autoimmune thyroiditis in 22 (33.3%), follicular adenoma isolated in five (7.6%), Hurthle cell adenoma in two (3.0%). Sixteen patients (24.2%) had more than one histopathological diagnosis. Permanent injury of the recurrent nerve was observed in one patient (1.5%). There was no case of permanent hypoparathyroidism. There was no operative mortality. CONCLUSION: Total thyroidectomy is an operation that can be safely performed, with low incidence of permanent complications, which allows one to broaden its indications in various benign thyroid diseases, thus avoiding future recurrences and reoperations.