Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study.

BACKGROUND: Hidradenitis suppurativa (HS), an inflammatory-based dermatological condition often associated with obesity, poses significant challenges in management. The very low-calorie ketogenic diet (VLCKD) has shown efficacy in addressing obesity, related metabolic disorders, and reducing chronic inflammation. However, its effects on HS remain underexplored. In this prospective pilot study, we aimed to investigate the impact of a 28-day active phase of VLCKD on HS in a sample of treatment-naive women with HS and excess weight. METHODS: Twelve women with HS and overweight or obesity (BMI 27.03 to 50.14 kg/m2), aged 21 to 54 years, meeting inclusion/exclusion criteria and agreeing to adhere to VLCKD, were included. Baseline lifestyle habits were assessed. The Sartorius score was used to evaluate the clinical severity of HS. Anthropometric parameters (waist circumference, weight, height, and body mass index), body composition via bioelectrical impedance analysis, levels of trimethylamine N-oxide (TMAO), oxidized low-density lipoprotein (oxLDL), and derivatives of reactive oxygen metabolites (dROMs) were assessed at baseline and after 28 days of the active phase of VLCKD. RESULTS: VLCKD led to general improvements in anthropometric parameters and body composition. Notably, a significant reduction in the Sartorius score was observed after the intervention (Δ%: - 24.37 ± 16.64, p < 0.001). This reduction coincided with significant decreases in TMAO (p < 0.001), dROMs (p = 0.001), and oxLDL (p < 0.001) levels. Changes in the Sartorius score exhibited positive correlations with changes in TMAO (p < 0.001), dROMs (p < 0.001), and oxLDL (p = 0.002). CONCLUSION: The 28-day active phase of VLCKD demonstrated notable improvements in HS severity and associated metabolic markers, highlighting the potential utility of VLCKD in managing HS and its association with metabolic derangements in women with overweight or obesity.

Melatonin decreases plasma TNF-α and improves nonenzymatic antioxidant defence and insulin sensitivity in rats with apical periodontitis fed a high-fat diet.

AIM: To analyse the effects of melatonin (ME) treatment on oxidative stress and insulin resistance (IR) in rats with apical periodontitis (AP) fed a high-fat diet (HFD). METHODOLOGY: Eighty 60-day-old rats were divided into eight groups: control (CN), AP, HFD with AP (HFDAP), control with ME (CNME), AP with ME (APME), HFD with ME (HFDME) and HFD with AP+ME (HFDAPME). The animals from the HFD groups were fed a HFD throughout the experimental period. On day 7, the animals from the AP groups were subjected to experimental AP, and after 70 days, the ME groups were treated for 30 days. Glycaemia, insulinaemia, homeostatic model assessment for IR index, tumour necrosis factor-α (TNF-α), and interleukin-6 were analysed in plasma using biochemical tests and enzyme-linked immunosorbent assay. Thiobarbituric acid-reactive substances (TBARS), carbonyl protein (CP), superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione (GSH) and total antioxidant capacity (ferric reducing antioxidant power [FRAP]) were analysed in the gastrocnemius muscle. RESULTS: (1) Association of AP and HDF exacerbated IR, and ME treatment improved this alteration; (2) AP and HFD and their association showed increased TNF-α, and ME reversed it; (3) TBARS increased in the AP and HFDAP groups, and ME reversed only in the group with the association of disease and diet; (4) CP increased in all HFD groups and improved in the ME groups; (5) GSH activity decreased in all experimental groups, and ME increased this parameter only in the CN and AP groups; (6) FRAP did not change between the groups, but ME treatment increased its activity in the AP and HFD groups; (7) ME increased SOD in the CN and AP groups. CONCLUSION: Apical periodontitis and HFD promoted IR, and the association of AP with diet promoted IR exacerbation; this resistance might have been caused by an increase in TNF-α. AP promoted more intense changes in lipid oxidative damage than in protein oxidative damage. In non-enzymatic antioxidant defence, it was observed that both AP and HFD and their association promoted a decrease in GSH levels. Overall, ME treatment reversed changes such as oxidative stress and IR.

Melatonin decreases IRF-3 protein expression in the gastrocnemius muscle, reduces IL-1ß and LPS plasma concentrations, and improves the lipid profile in rats with apical periodontitis fed on a high-fat diet.

To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-ß (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1ß (IL-1ß) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL. HFD groups were fed on a HFD for 107 days. On day 7, experimental AP was induced in the AP groups, and after 70 days, MEL (5 mg/kg) was administered to the MEL groups for 30 days. Plasma concentrations of LPS and IL-1ß were analyzed using enzyme-linked immunosorbent assay, and the lipid profile was analyzed using biochemical tests. The expression of proteins involved in the TLR4 pathway (TLR4, MyD88, TRIF, IRF-3 and NF-κB) in the gastrocnemius muscle (GM) was evaluated using western blotting and qRT-PCR. Treatment with MEL decreased IRF-3 protein expression in GM and IL-1ß plasma concentration in the APMEL and HFDMEL groups. Reduction in LPS plasma concentration was reported only in the HFDMEL group. Additionally, a decrease in LDL and an increase in HDL were observed in the HFDMEL and HFDAPMEL groups. Treatment with MEL exhibited anti-inflammatory and anti-hyperlipidemic effects attributed to HFD and AP by reducing the plasma concentrations of IL-1ß and LPS in addition to reducing IRF-3 protein expression in the GM, which is associated with the production of inflammatory cytokines.

Effect of maternal apical periodontitis on the final step of insulin signalling and inflammatory pathway in the adult male offspring of rats.

AIM: To evaluate the final step of insulin signalling, inflammatory pathway (related to the inhibition of insulin signalling), peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) protein content and DNA methylation in the Slc2a4 gene promoter region in the skeletal muscle of adult male offspring of rats with apical periodontitis (AP) in a single tooth or in four teeth. METHODOLOGY: Female Wistar rats were distributed into three groups: a control group, a group with one tooth with AP and a group with four teeth with AP. Thirty days after induction of AP, female rats from all groups were mated with healthy male rats. When male offspring reached 75 days of age, the following analyses were performed in the gastrocnemius muscle (GM): insulin-stimulated Akt serine and threonine phosphorylation status; NF-κB p50 and p65 subunits phosphorylation status; GLUT4, TNF-α and PGC-1α protein content by Western blotting; GLUT4 and TNF-α gene expression by real-time polymerase chain reaction (PCR); and DNA methylation in the Slc2a4 gene promoter region by restriction digestion and real-time PCR. Analysis of variance was performed, followed by Tukey's post hoc test. p values <.05 were considered to be statistically significant. RESULTS: Maternal AP in four teeth decreased insulin-stimulated Akt serine and threonine phosphorylation status, reduced GLUT4 gene expression and its protein content, and increased NF-κB p50 and p65 subunits phosphorylation status in the GM of adult offspring. There were no alterations in the parameters analysed in the GM of adult offspring of rats with AP in a single tooth. In addition, maternal AP did not affect TNF-α gene expression and its protein content, PGC-1α protein content and DNA methylation in the Slc2a4 gene promoter region in the GM of adult offspring. CONCLUSIONS: Maternal AP in four teeth was associated with impairment in the final step of insulin signalling in the GM of adult male offspring in rats. An increase in NF-κB activity may be involved in this decrease in insulin signalling. This study demonstrates the impact of maternal AP on the health of offspring, demonstrating the importance of maintaining adequate maternal oral health to prevent diseases in adult offspring in rats.

Molecular bases of responses to abiotic stress in trees.

Trees are constantly exposed to climate fluctuations, which vary with both time and geographic location. Environmental changes that are outside of the physiological favorable range usually negatively affect plant performance and trigger responses to abiotic stress. Long-living trees in particular have evolved a wide spectrum of molecular mechanisms to coordinate growth and development under stressful conditions, thus minimizing fitness costs. The ongoing development of techniques directed at quantifying abiotic stress has significantly increased our knowledge of physiological responses in woody plants. However, it is only within recent years that advances in next-generation sequencing and biochemical approaches have enabled us to begin to understand the complexity of the molecular systems that underlie these responses. Here, we review recent progress in our understanding of the molecular bases of drought and temperature stresses in trees, with a focus on functional, transcriptomic, epigenetic, and population genomic studies. In addition, we highlight topics that will contribute to progress in our understanding of the plastic and adaptive responses of woody plants to drought and temperature in a context of global climate change.

The importance of drug safety and tolerability in the development of new immunosuppressive therapy for transplant recipients: The Transplant Therapeutics Consortium's position statement.

The Transplant Therapeutics Consortium (TTC) is a public-private partnership between the US Food and Drug Administration and the transplantation community including the transplantation societies and members of the biopharmaceutical industry. The TTC was formed to accelerate the process of developing new medical products for transplant patients. The initial goals of this collaboration are the following: (a) To define which aspects of the kidney transplant drug-development process have clear needs for improvement from an industry and regulatory perspective; (b) to define which of the unmet needs in the process could be positively impacted through the development of specific drug-development tools based on available data; and (c) to determine the most appropriate pathway to achieve regulatory acceptance of the proposed process-accelerating tools. The TTC has identified 2 major areas of emphasis: new biomarkers or endpoints for determining the efficacy of new therapies and new tools to assess the safety or tolerability of new therapies. This article presents the rationale and planned approach to develop new tools to assess safety and tolerability of therapies for transplant patients. We also discuss how similar efforts might support the continued development of patient-reported outcome measures in the future.

Vitamin D Intake and Magnetic Resonance Parameters for Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

PURPOSE: There is evidence that vitamin D may play a role in the osteoarthritis (OA) pathogenesis, but the few data available are limited to X-rays and clinical findings. The aim of this study was to investigate whether a higher intake of vitamin D was associated with a better architecture of the cartilage of the knee, assessed with magnetic resonance (MRI), in a large cohort from North America. METHODS: 783 participants (59.8% females; mean age: 62.3 years) with an MRI assessment from the Osteoarthritis Initiative were included. Vitamin D dietary intake was calculated as the sum of food and oral supplementation. A coronal 3D FLASH with Water Excitation MR sequence of the right knees was used. The strength of the association between dietary vitamin D intake and knee MRI parameters was investigated through an adjusted linear regression analysis, reported as standardized betas with 95% confidence intervals (CIs). RESULTS: Using a linear regression analysis, adjusted for ten potential confounders, higher vitamin D intake (reported as an increase in one standard deviation, = 250 IU) corresponded to significantly higher values of mean cartilage thickness and volume of cartilage at medial tibia, volume of cartilage and mean cartilage thickness at central lateral femur, volume of cartilage and mean cartilage thickness at central medial femur, and volume of cartilage and mean cartilage thickness at central medial tibial-femoral compartment. CONCLUSIONS: Higher vitamin D intake is associated with a significantly better architecture of the cartilage of the knee, also independently taking in account from several potential confounders.

Validation of the shortened Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS).

BACKGROUND: The rare disease, Hunter Syndrome (mucopolysaccharidosis type II; MPS II), characterized by iduronate-2-sulfatase deficiency, has heterogeneous symptoms often including cognitive impairment (CI). To evaluate physical functioning and daily activity limitations of patients with MPS II, the multidomain shortened Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) questionnaire was previously developed and preliminarily validated. Here we gather data in a dedicated prospective longitudinal observational study using direct responses to the shortened instrument and assess its psychometric properties further. METHODS: Interview data were collected from eligible self-reporting patients (≥ 12 years of age) or caregivers of patients using respective versions of the instrument at baseline and 2-4 weeks later. Internal consistency, test-retest reliability, convergent and discriminant validity, and validity of known groups were assessed. Participants also completed Child Health Questionnaire (CHQ), Health Utilities Index Mark 3, and Global Impression of Severity (GIS) questionnaires. RESULTS: All patients were male, consisting of 31 caregiver-reported patients (aged 3-26 years) and 20 self-reported patients (aged 12-58 years). Most (77.4%) caregiver-reported patients had CI. Both questionnaire versions demonstrated good internal consistency and test-retest reliability; Cronbach's alpha and intra-class correlation coefficients were > 0.70. Spearman's correlations demonstrated good convergent validity with moderate (> 0.3) to high (> 0.6) correlations of the HS-FOCUS total score with physical functioning, role/social-physical, and bodily pain domains of CHQ. The tool also differentiated between MPS II severity levels based on GIS scores. CONCLUSIONS: The shortened HS-FOCUS questionnaire was found to be a valid and reliable tool to assess the physical functioning impact of MPS II.

Periapical lesions decrease Akt serine phosphorylation and plasma membrane GLUT4 content in rat skeletal muscle.

OBJECTIVES: Periapical lesion (PL) promotes insulin resistance; however, the mechanisms underlying this alteration are not fully understood. Therefore, in this study, we aimed to evaluate the Akt serine phosphorylation status and GLUT4 expression levels in the gastrocnemius muscle (GM) of rats with PL. MATERIALS AND METHODS: Male Wistar rats (n = 42) were distributed equally into control (CN) and PL groups. The pulpal tissue of the PL group rats was exposed to the oral environment for 30 days. Thereafter, glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). The Akt serine phosphorylation and GLUT4 levels of microsomal (M) and plasma membrane (PM) fractions were evaluated by western blotting and analyzed statistically. RESULTS: Compared to CN group rats, PL group rats had lower insulin sensitivity (as observed by HOMA-IR), lower Akt serine phosphorylation status after insulin stimulus, and lower GLUT4 levels in the PM fraction. However, the M fraction in the PL group did not differ significantly from that of the CN group. CONCLUSIONS: PL decreases insulin sensitivity, Akt phosphorylation, and PM GLUT4 content. CLINICAL RELEVANCE: The present study indicates that preventing endodontic disease can thwart insulin resistance.

Symptoms and markers of symptom severity in asthma--content validity of the asthma symptom diary.

BACKGROUND AND OBJECTIVES: The American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force acknowledged the multi-faceted nature of asthma in its recent definition of asthma control as a summary term capturing symptoms, reliever use, frequency/severity of exacerbations, lung function, and future risk and the Global Initiative for Asthma (GINA) defines the clinical manifestations (well established markers of asthma severity) of asthma to include symptoms, sleep disturbances, limitations of daily activity, impairment of lung function, and use of rescue medications. The objectives of this qualitative work were to identify symptoms and markers of symptom severity relevant to patients with moderate to severe asthma and to evaluate the content validity of the asthma symptom diary (ASD). METHODS: A qualitative interview study was conducted using a purposive sample of symptomatic adult and adolescent (≥12 years) subjects with asthma. Concept elicitation (CE) interviews (n = 50) were conducted to identify core asthma symptoms and symptom-related clinical markers, followed by cognitive interviews (n = 24) to ensure patient comprehension of the items, instructions and response options. CE interviews were coded using ATLAS.ti for content analysis. RESULTS: The study sample had a diverse range of symptom severity, level of symptom control, sociodemographic and socioeconomic status. The most frequently reported symptoms in adults were chest tightness (n = 33/34; 97.1%), wheezing (n = 31; 91.2%), coughing (n = 30; 88.2%), and shortness of breath (n = 25; 73.5%); in adolescents they were wheezing (n = 14/16; 87.5%), coughing (n = 13; 81.3%), and chest tightness (n = 11; 68.8%). Adults identified chest tightness followed by shortness of breath as their most severe symptoms; while adolescents reported coughing and chest tightness as their most severe symptoms. Sleep awakenings and limitations in day-to-day activities were frequent symptom-related clinical markers. Day-to-day variability and differences between daytime and nighttime symptom experiences reported by subjects resulted in the need for the ASD to be administered twice daily. Cognitive interviews indicated that subjects found the revised ASD items clear and easy to understand. CONCLUSIONS: This study supports the content validity of the revised ASD, showing it to be consistent with patient experiences and ready for further psychometric testing.

The Burden of Pruritus Associated With CKD: A Mixed Methods Analysis Among Patients Undergoing Dialysis.

Rationale & Objective: Despite its prevalence and distress to patients, chronic kidney disease-associated pruritus (CKD-aP) is poorly characterized, which may contribute to the condition's underdiagnosis and inadequate management. This study aimed to understand the symptom experience of patients with CKD-aP and the extent to which pruritus impacts their lives. Study Design: Mixed methods study including one-on-one qualitative interviews and completion of the Skindex-10 Questionnaire (measuring itch-related quality of life). Setting & Participants: A total of 23 patients undergoing hemodialysis and reporting pruritus at 4 dialysis centers in the United States. Analytical Approach: Interviews followed a semistructured guide that included targeted and follow-up questions to elicit discussion of patients' symptoms of pruritus, including frequency and variability, impact on activities of daily living, and emotional and social functioning. Interviews were digitally audio-recorded. A coding dictionary was developed from transcripts to analyze themes and concepts. Results: Participants described their itch with various terms, including "numbness," "pain," and "tingling" on their skin. Itch affected multiple areas but especially the back, usually occurred daily, and was often worse at night. For some, itching was a constant experience. Patients relieved their itch through scratching and various off-label treatments; some reported skin damage from excessive scratching and most indicated treatments provided limited relief. Pruritus considerably disrupted physical function, including sleep, daily activities, social functioning and relationships, and emotional and psychological wellbeing. All participants reported being bothered by their itching during the past week on the Skindex-10 Questionnaire. Limitations: All participants were from the United States, so the findings may not be generalizable to other countries. Conclusions: Although symptom experience varies considerably, CKD-aP causes severe distress for many patients undergoing hemodialysis and can profoundly impair their quality of life. The results of this study show the impact of itch from patients' perspectives and highlight the need for greater awareness and better management of this condition. Plain-Language Summary: Patients with chronic kidney disease often experience itching, or pruritus, but its importance to patients is regularly overlooked. This study used one-on-one interviews to investigate patients' experiences of chronic kidney disease-associated pruritus and how it impacts their lives. We found that participants experienced itch on various body areas and used different words to describe their itch (eg, "numbness" and "pain"). Some reported skin damage from excessive scratching, and many used off-label treatments and other interventions (eg, rubbing alcohol and multiple showers daily), which provided limited relief. For many, itching was experienced daily and severely disrupted sleep, daily activities, interactions with others, and mental wellbeing. These findings reveal chronic kidney disease-associated pruritus severely impacts patients and highlights the need for improved management of this condition.

Modulatory influence of melatonin on apical periodontitis in Wistar rats fed a high-fat diet.

OBJECTIVE: This study aimed to evaluate the influence of high-fat diet (HFD) and melatonin (MEL) treatment on the progression of inflammation and alveolar bone resorption (ABR) in rats with AP. DESIGN: Forty male Wistar rats were divided into four groups: apical periodontitis (AP), HFDAP, APMEL and HFDAPMEL. The animals were fed an HFD or standard diet for 107 days. On the 7th day, the rats were subjected to AP, and after 70 days, the rats in the MEL groups were treated with MEL for 30 days. Post treatment, the animals were euthanized, and their jaws were retrieved for evaluation of bone resorption, intensity of the inflammatory response, and immunohistochemical analysis including tartrate-resistant acid phosphatase (TRAP) and interleukin-1ß (IL-1ß) levels and tumor necrosis factor (TNF)-α expression. RESULTS: The APMEL group showed reduction in the inflammatory infiltrate and IL-1ß expression relation to HFDAP, while the TNF-α levels did not differ among the groups. The HFDAP group showed an increase in the ABR. MEL reduced the TRAP levels in the APMEL and HFDAPMEL groups. CONCLUSIONS: while MEL could reduce TRAP levels in the APMEL and HFDAPMEL groups, the reduction in the HFDAPMEL group was smaller than that in the APMEL group, demonstrating that the interaction between AP and HFD decreased the anti-resorptive effects of MEL.

Effect of maternal true combined endodontic-periodontal lesion on insulin and inflammatory pathway in adult offspring.

BACKGROUND: Maternal periodontal disease (PED) and apical periodontitis (AP) are associated insulin resistance (IR), increased tumor necrosis factor-α (TNF-α) levels, and alterations in insulin signaling (IS) in the gastrocnemius muscle (GM) of adult offspring. TNF-α stimulates I kappa B kinase (IKK) and c-Jun N-terminal protein kinase (JNK), resulting in IS attenuation. However, studies that investigated the maternal true endodontic-periodontal lesion (EPL) in offspring are scarce, and in this case, the impact could be even higher. This study aimed to evaluate the effects of EPL on the IR, IS, and inflammatory pathways on the offspring GM. METHODS: Female Wistar rats were distributed into control, AP, PED, and EPL groups. After 30 days of oral inflammation induction, rats from all groups were allowed to mate with healthy rats. The body weight of the offspring was assessed from birth to 75 days of age. After 75 days, the following measurements were performed: glycemia, insulinemia, IR, TNF-α content, and IKKα/ß, JNK, pp185 (Tyr), and IRS-1 (Ser) phosphorylation status in the GM. RESULTS: Maternal PED and EPL were associated with low birth weights. All maternal oral inflammations promoted IR and IS impairment in the GM and only maternal PED and EPL caused an increase in TNF-α content and IKKα/ß phosphorylation status in the GM of offspring. The offspring of the rats with EPL group showed worsening of metabolic changes when compared with offspring of rats with AP or PED. CONCLUSION: Association of maternal AP and PED promoted a more pronounced worsening in the health of the adult offspring.

The anemia impact measure (AIM): development and content validation of a patient-reported outcome measure of anemia symptoms and symptom impacts in cancer patients receiving chemotherapy.

PURPOSE: To develop a patient-reported outcome instrument for measuring anemia symptoms and their impact in patients with chemotherapy-induced anemia (CIA). METHODS: Qualitative research was conducted using six focus groups and 24 interviews with 46 CIA patients, eight interviews in patients receiving chemotherapy with no CIA history and two interviews in patients successfully treated for CIA. Atlas.ti 5.0 was used to organize key concepts. Cognitive interviews with 16 CIA patients and assessment of relevance of each item to CIA by 10 clinicians were also conducted to evaluate content validity. RESULTS: Most CIA patients were white (76%) and female (83%), and the average age was 60 years. The most common cancer types were breast cancer (54%) and lung cancer (17%). Tiredness was the most prevalent symptom and rated as the most important by 83% of CIA patients; weakness, shortness of breath, lightheadedness, and dizziness were ranked next in importance. The final anemia impact measure (AIM) contains: (1) daily CIA symptom diary (9 items), and (2) impact of CIA-related tiredness (29 items covering daily living activities, social activities, cognitive function, and emotions). Cognitive interviews found that the AIM was relevant and easy to understand. CONCLUSIONS: The AIM assesses important patient-perceived CIA symptoms and their impact and was developed using extensive patient qualitative data.

Assessment of redox state and biochemical parameters of salivary glands in streptozotocin-induced diabetic male rats treated with mate tea (Ilex paraguariensis).

OBJECTIVE: The study aimed to assess the effects of mate tea [Ilex paraguariensis] on the redox state and biochemical parameters of salivary glands in diabetic male rats. DESIGN: Twenty-four male Wistar rats (3 months old) were randomly divided into groups (n = 8 per group): control rats that received water (C); diabetic rats that received water (D); diabetic rats treated with mate tea (DMT). The treated streptozotocin-induced diabetic rats were given mate tea powder by intragastric gavage at a dose of 20 mg/kg daily for 28 days. Content of total protein, amylase, oxidative lipid damage, measured as thiobarbituric acid reactive substances (TBARs), oxidative protein damage, measured as protein carbonyl, total antioxidant capacity, uric acid, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were examined by the spectrophotometric method in the parotid and submandibular glands. RESULTS: The D group showed lower total protein, amylase, TBARs, protein carbonyl, total antioxidant capacity, GSH, uric acid, and GPx than the C group in both salivary glands, as well as higher SOD and CAT activities. The DMT group showed higher total protein, amylase, total antioxidant capacity, GSH, uric acid, and GPx than the D group in both salivary glands. Moreover, mate tea increased SOD in the parotid gland and CAT in the submandibular gland of diabetic rats but did not influence TBARs and protein carbonyl in either salivary gland compared to D group. CONCLUSION: Mate tea increased tissue protein synthesis and improved antioxidant defenses in the salivary glands of streptozotocin-induced diabetic male rats.

Maternal Apical Periodontitis Increases Insulin Resistance and Modulates the Antioxidant Defense System in the Gastrocnemius Muscle of Adult Offspring.

INTRODUCTION: Maternal apical periodontitis (AP) is associated with insulin resistance (IR) in adult offspring. Oxidative stress has been linked to IR. This study investigated insulin sensitivity (IS) and oxidative stress in the gastrocnemius muscle (GM) of adult offspring of rats with AP. METHODS: Fifteen female Wistar rats were distributed into a control group, a group with 1 tooth with AP, and a group with 4 teeth with AP. Thirty days after AP induction, female rats were mated with healthy male rats. When male offspring reached 75 days of age, glycemia, insulinemia, and IS were determined. In the GM, the oxidative damage products (thiobarbituric acid reactive substances and carbonyl protein) and activities of enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (glutathione and total antioxidant capacity) antioxidants were quantified. Analysis of variance was performed followed by the Tukey post hoc test (P < .05). RESULTS: Maternal AP was associated with decreased IS and changes in antioxidant activities (reduced superoxide dismutase and increased catalase, glutathione peroxidase, and glutathione) and decreased thiobarbituric acid reactive substance concentration in the GM of their adult offspring. However, maternal AP does not appear to affect glycemia, carbonyl protein concentration, and the nonenzymatic total antioxidant capacity in the GM of this offspring. CONCLUSIONS: Maternal AP modulates the antioxidant defense system in the GM of their adult offspring, attenuating lipid peroxidation in this tissue. This reflects part of an adaptive response of the offspring to the stimulation of the maternal chronic oral inflammatory process in which the organism acts by decreasing oxidative tissue damage in the postnatal stage. The present study improves knowledge about the impact of maternal oral inflammation on healthy offspring.

Late-in-life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts.

Protein quality control mechanisms decline during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age-associated cardiac dysfunction. Macroautophagy is the process by which post-mitotic cells such as cardiomyocytes clear defective proteins and organelles. We hypothesized that late-in-life exercise training improves autophagy, protein aggregate clearance, and function that is otherwise dysregulated in hearts from old vs. adult mice. As expected, 24-month-old male C57BL/6J mice (old) exhibited repressed autophagosome formation and protein aggregate accumulation in the heart, systolic and diastolic dysfunction, and reduced exercise capacity vs. 8-month-old (adult) mice (all p < 0.05). To investigate the influence of late-in-life exercise training, additional cohorts of 21-month-old mice did (old-ETR) or did not (old-SED) complete a 3-month progressive resistance treadmill running program. Body composition, exercise capacity, and soleus muscle citrate synthase activity improved in old-ETR vs. old-SED mice at 24 months (all p < 0.05). Importantly, protein expression of autophagy markers indicate trafficking of the autophagosome to the lysosome increased, protein aggregate clearance improved, and overall function was enhanced (all p < 0.05) in hearts from old-ETR vs. old-SED mice. These data provide the first evidence that a physiological intervention initiated late-in-life improves autophagic flux, protein aggregate clearance, and contractile performance in mouse hearts.

Effect of resistance training on osteopenic rat bones in neonatal streptozotocin-induced diabetes: Analysis of GLUT4 content and biochemical, biomechanical, densitometric, and microstructural evaluation.

AIMS: To investigate the effect of resistance training-RT on glycemia, expression of the glucose transporter-GLUT4, bone mineral density-BMD, and microstructural and biomechanical properties of osteopenic rat bones in neonatal streptozotocin-induced diabetes. MAIN METHODS: Sixty-four 5-day-old male rats were divided into two groups: control and diabetic rats injected with vehicle or streptozotocin, respectively. After 55 days, densitometric analysis-DA of the tibia was performed. These groups were subdivided into four subgroups: non-osteopenic control-CN, osteopenic control-OC, non-osteopenic diabetic-DM, and osteopenic diabetic-OD. The OC and OD groups were suspended by their tails for 21 days to promote osteopenia in the hindlimb; subsequently, a second DA was performed. The rats were subdivided into eight subgroups: sedentary control-SC, sedentary osteopenic control-SOC, exercised control-EC, exercised osteopenic control-EOC, sedentary diabetic-SD, sedentary osteopenic diabetic-SOD, exercised diabetic-ED, and exercised osteopenic diabetic-EOD. For RT, the rats climbed a ladder with weights secured to their tails for 12 weeks. After RT, a third DA was performed, and blood samples, muscles, and tibias were assessed to measure glycemia, insulinemia, GLUT4 content, bone maximum strength, fracture energy, extrinsic stiffness, BMD, cancellous bone area, trabecular number, and trabecular width. KEY FINDINGS: After RT, glycemia, GLUT4 content, BMD, and bone microstructural and biomechanical properties were improved in diabetic rats (osteopenic and non-osteopenic). However, RT had no effect on these parameters in the EC and SC groups. SIGNIFICANCE: These results suggest that RT improves GLUT4 content, BMD, and microstructural and biomechanical properties of bone in osteopenic and non-osteopenic diabetic rats and is effective in controlling glycemia.

Apical periodontitis promotes insulin resistance and alters adaptive immunity markers in rats.

OBJECTIVE: Apical periodontitis (AP) is a chronic or acute inflammatory disease usually developed from endodontic infections, predominantly due to gram-negative anaerobic bacteria invading the dental pulp. This study aimed to evaluate lymphocyte markers to assess the involvement of adaptive immunity in insulin resistance (IR) in a rat model of AP.Design.Forty-five male Wistar albino rats were divided into 3 groups (control, 1AP and 4AP). AP was induced in the upper right first molar (1AP), and in the first and second upper and lower right molars (4AP). The spleen was collected to evaluate the expression of transcription factors involved in lymphocyte polarization, including T-bet (Th1), GATA3 (Th2), and FOXP3 (Treg). Blood samples were assessed for serum cytokine levels transcribed by the respective lymphocyte polarizations, INF-γ (Th1), IL-4 (Th2) and TGF-ß (Treg). In addition, glucose and insulin levels were measured to evaluate IR by the HOMA-IR method. RESULTS: The results showed higher T-bet expression on AP groups, along with lower GATA3 and FOXP3 expression in the 1AP, in addition to increased GATA3 and decreased FOXP3 expression in the 4AP group compared to the CN group. There was no difference in the INF-γ levels, while IL-4 was decreased in the AP groups. Taken together, these results suggest that the adaptive immune system, with a predominance of the Th1 polarization, may be involved in the development of IR in rats with AP. CONCLUSIONS: AP promotes increase in the expression of T-bet (4AP) and decrease of FOXP3 expressions and IL-4 levels (1AP and 4AP). However, depending on the number of lesions (1 or 4 lesions), the expression of GATA3 appears differently. Thus, innate immunity and adaptive immunity may contribute to the IR observed in rats with AP.

Reduction in opioid-related adverse events and improvement in function with parecoxib followed by valdecoxib treatment after non-cardiac surgery: a randomized, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Multimodal pain therapy including cyclo-oxygenase-2 inhibitors can result in optimal pain management with decreased opioid use and fewer opioid-related adverse events. Patient reported outcomes (PROs) help identify benefits in reduced opioid use and increased pain control. METHODS: In this randomized, double-blind trial, patients (n = 1062) undergoing major non-cardiac elective surgery received either parenteral parecoxib for 3 days or placebo then oral valdecoxib or placebo for a total of 10 days, with both arms being allowed additional opioid analgesia. Clinically meaningful opioid-related adverse events were assessed daily using the Opioid-Related Symptom Distress Scale (OR-SDS). Pain severity and interference with function were evaluated daily using the modified Brief Pain Inventory exploratory form (mBPI-e). Additional validation work was undertaken to understand the psychometric properties of the two PROs. Detailed clinical results were reported elsewhere. RESULTS: Patients receiving parecoxib/valdecoxib achieved significantly better pain control and consumed 37% and 28% less opioid medication than the placebo group on day 2 and day 3, respectively. Over the 10-day treatment period, patients receiving parecoxib/valdecoxib consumed 31% less opioid medication. This coincided with significantly fewer (p < 0.0001) OR-SDS clinically meaningful events (CMEs) and lower mBPI-e scores from days 2-10 in the parecoxib/valdecoxib group compared with the placebo group. On day 3, the percentage of patients reporting one, two or three CMEs in the parecoxib/valdecoxib versus placebo group was 11.6% versus 13.0%, 2.3% versus 5.1%, and 0.8% versus 2.3%, respectively. The mean (+/- standard error) mBPI-e pain severity scores over days 2-10 were 2.47 +/- 0.04 for the parecoxib/valdecoxib group and 3.01 +/- 0.04 for the placebo group, and the mean mBPI-e pain interference scores were 1.73 +/- 0.04 and 2.19 +/- 0.04, respectively. CONCLUSIONS: Patients receiving parecoxib/valdecoxib had less pain interference on physical functioning, required less opioid medication and experienced fewer clinically meaningful opioid-related adverse events than patients receiving placebo.