Pedometer- and accelerometer- based physical activity interventions in Type 2 diabetes: A systematic review and meta-analysis.

AIMS: Although accelerometer- and pedometer-based physical activity (PA) interventions can increase PA, there is no solid evidence for their benefits in patients with type 2 diabetes (T2DM). The aim of this systematic review and meta-analysis of randomized controlled clinical trials (RCTs) was to determine the effects of accelerometer- and pedometer-based PA interventions on hemoglobin A1c (HbA1c), fasting glucose, weight, BMI, blood pressure, lipids, and PA in adults with T2DM. DATA SYNTHESIS: Records from MEDLINE/PubMed, EMBASE, LILACS, and Scopus were searched from inception through March 28th, 2022. RCTs of at least two weeks of duration evaluated the effectiveness of pedometers or accelerometers as motivating tools for increasing PA in T2DM patients. This study was registered with PROSPERO and followed the PRISMA reporting guide. Of the 7131 non-duplicated articles retrieved, 24 RCTs (1969 patients) were included. The mean baseline HbA1c of the experimental group of included studies varied from 6.3 ± 0.9 % to 9.0 ± 0.01 %. The accelerometer- and pedometer-based PA interventions resulted in a greater improvement in HbA1c (-0.22 %; 95%CI, -0.4 % to -0.05 %; I2 = 77 %) and triglycerides (-13.11 mg/dL; 95%CI, -25.21 to -1.02; I2 = 22 %) versus control participants. Pedometer ambulatory use as a motivating tool significantly increased PA by 2,131 steps/day (95 % CI, 1,348 to 2,914; I2 = 74 %) in T2DM patients. CONCLUSIONS: Pedometers and accelerometers are associated with reductions in HbA1c and triglycerides when used as motivating tools. Larger and higher-quality studies are required to determine the full effects of PA as motivated by trackers in T2DM population.

Thyroid hormone receptor phosphorylation regulates acute fasting-induced suppression of the hypothalamic-pituitary-thyroid axis.

Fasting induces profound changes in the hypothalamic-pituitary-thyroid (HPT) axis. After binding thyroid hormone (TH), the TH receptor beta 2 isoform (THRB2) represses Trh and Tsh subunit genes and is the principle negative regulator of the HPT axis. Using mass spectrometry, we identified a major phosphorylation site in the AF-1 domain of THRB2 (serine 101, S101), which is conserved among many members of the nuclear hormone receptor superfamily. More than 50% of THRB2 is phosphorylated at S101 in cultured thyrotrophs (TαT1.1) and in the mouse pituitary. All other THR isoforms lack this site and exhibit limited overall levels of phosphorylation. To determine the importance of THRB2 S101 phosphorylation, we used the TαT1.1 cell line and S101A mutant knock-in mice (Thrb2S101A ). We found that TH promoted S101 THRB2 phosphorylation and was essential for repression of the axis at physiologic TH concentrations. In mice, THRB2 phosphorylation was also increased by fasting and mimicked Trh and Tshb repression by TH. In vitro studies demonstrated that a master metabolic sensor, AMP-activated kinase (AMPK) induced phosphorylation at the same site and caused Tshb repression independent of TH. Furthermore, we identified cyclin-dependent kinase 2 (CDK2) as a direct kinase phosphorylating THRB2 S101 and propose that AMPK or TH increase S101 phosphorylation through the activity of CDK2. This study provides a physiologically relevant function for THR phosphorylation, which permits nutritional deprivation and TH to use a common mechanism for acute suppression of the HPT axis.

In vivo exposure to pyriproxyfen causes ovarian oxidative stress and inhibits follicle maturation in zebrafish.

We analyzed the effects of pyriproxyfen (PPF) on oxidative stress and ovarian morphology in zebrafish. PPF (10-9  M) exposure increased reactive oxygen species generation in ovaries, in association with a decrease in glutathione content. The activities of glutathione S-transferase, superoxide dismutase, and catalase were increased, while γ-glutamyltransferase activity was not altered by pesticide treatment. The histology of ovarian tissue showed an increase in the number of previtellogenic oocytes I, and a decrease in the rate of vitellogenic oocyte (VIT) count, suggesting inhibition of follicular maturation. An increase in the thickness of the vitelline envelope was observed in VIT, as was a tendency toward an increase in atresia in the ovary of the PPF-treated group. These findings indicate that the deleterious effect of PPF on ovarian maturation is mediated by a redox imbalance and oxidative damage. So, PPF acts as an endocrine disruptor chemical and may compromise fish reproduction by reducing female fertility.

Translation, cross-cultural adaptation, validity and reliability of the Brazilian Portuguese version of Activity Scale for Kids questionnaire.

BACKGROUND: The Activity Scale for Kids (ASK) assesses the physical disability of children (5 to 15 years old) with neurological, orthopaedic or rheumatic diseases. The objective of this study was to translate and cross-culturally adapt the ASK for Brazilian Portuguese and assess the validity and reliability of the instrument. METHODS: A total of 67 children and adolescents with musculoskeletal, neurological or rheumatic diseases participated in the study. We evaluated the comprehension of the pre-final version of the questionnaire in 24 participants and reliability and validity in the other 43 participants. The translation and adaptation of ASK to Brazilian Portuguese followed guidelines from previous studies. The validity of the Brazilian Portuguese version of the ASK was verified through Spearman's correlation with the Pediatric Quality of Life Inventory™ Version 4.0 (PedQL). Intraclass correlation coefficient verified inter- and intra-evaluator reliability, while internal consistency was assessed using Cronbach's alpha. Scores were used to assess the standard error of the mean and minimal detectable change. RESULTS: The Brazilian Portuguese version of the ASK presented excellent reliability, internal consistency, agreement and moderate correlation with PedsQL (0.522, P < 0.001) between ASK performance and PedsQL; 0.537, P < 0.001 between ASK capacity and PedsQL. CONCLUSION: The Brazilian Portuguese version of the ASK has good validity and reliability and may be used by professionals and researchers to assess the functioning of children and adolescents with disabilities.

Combined conventional speech therapy and functional electrical stimulation in acute stroke patients with dyphagia: a randomized controlled trial.

BACKGROUND: Stroke is the main cause of oropharyngeal neurogenic dysphagia. Electrostimulation has been used as a therapeutic tool in these cases. However, there are few studies that prove its effectiveness. We evaluated the effect of functional electrostimulation as a complement to conventional speech therapy in patients with dysphagia after a stroke in a stroke unit. METHODS: We performed a clinical, randomized, and controlled trial divided into intervention group (IG) (n = 16) and control group (CG) (n = 17). All patients were treated with conventional speech therapy, and the IG also was submitted to the functional electrotherapy. Primary outcomes were Functional Oral Ingestion Scale (FOIS) and Swallowing videoendoscopy (FEES). The degree of dysphagia was scored in functional, mild, moderate and severe dysphagia according to FEES procedure. Dysphagia Risk Evaluation Protocol (DREP) was considered a secondary outcome. RESULTS: There was a significant difference regarding FOIS scores after 5 days of intervention in groups. Both groups also showed a tendency to improve dysphagia levels measured by FEES, although not statistically significant. Improvements on oral feeding was seen in both groups. No significant differences between groups before and after the intervention were detected by DREP scores. Electrical stimulation did not show additional benefits beyond conventional therapy when comparing outcomes between groups. CONCLUSION: Conventional speech therapy improved oral ingestion even regardless the use of electrostimulation in a stroke unit. TRIAL REGISTRATION: This research was registered in ClinicalTrials.gov (Identifier: NCT03649295 ) in 28/08/2018 and in the Brazilian Registry of Clinical Trials (ReBEC) (Register Number: RBR-56QK5J), approval date: 18/12/2018. HGF Ethics Committee Approval Number: N. 2.388.931.

Glutathione production by Saccharomyces cerevisiae: current state and perspectives.

Glutathione (L-γ-glutamyl-cysteinyl-glycine, GSH) is a tripeptide synthesized through consecutive enzymatic reactions. Among its several metabolic functions in cells, the main one is the potential to act as an endogenous antioxidant agent. GSH has been the focus of numerous studies not only due to its role in the redox status of biological systems but also due to its biotechnological characteristics. GSH is usually obtained by fermentation and shows a variety of applications by the pharmaceutical and food industry. Therefore, the search for new strategies to improve the production of GSH during fermentation is crucial. This mini review brings together recent papers regarding the principal parameters of the biotechnological production of GSH by Saccharomyces cerevisiae. In this context, aspects, such as the medium composition (amino acids, alternative raw materials) and the use of technological approaches (control of osmotic and pressure conditions, magnetic field (MF) application, fed-batch process) were considered, along with genetic engineering knowledge, trends, and challenges in viable GSH production. KEY POINTS: • Saccharomyces cerevisiae has shown potential for glutathione production. • Improved technological approaches increases glutathione production. • Genetic engineering in Saccharomyces cerevisiae improves glutathione production.

DASH diet vs. DASH diet plus physical activity in older patients with type 2 diabetes and high blood pressure: A randomized clinical trial.

BACKGROUND AND AIMS: To evaluate the effect of lifestyle modification by adopting a DASH diet, with and without physical activity guidance, on blood pressure, glycemic control, lipid profile, weight, and body composition in older patients with type 2 diabetes mellitus (T2DM) and hypertension. METHODS AND RESULTS: For this randomized clinical trial, we recruited patients aged 60 years or older with T2DM and uncontrolled hypertension. One group (DASH) received only DASH dietary guidance, while the other group (DASHPED) received dietary guidance and encouragement to walk with a pedometer. Outcomes of interest were (1) blood pressure, (2) physical activity, (3) weight, body mass index (BMI), and body composition, and (4) biochemical variables. Measurements were taken at baseline and 16 weeks after the intervention. We included 35 patients in the analysis. At the end of the study, the DASHPED group had an mean increase in physical activity of 1721 steps/day. Both groups displayed significantly reduced weight, BMI, and waking diastolic pressures on ambulatory blood pressure monitoring after the intervention. A trend of reduced sleeping diastolic pressure was found in the DASHPED group. Changes in weight, BMI, muscle mass, body fat, waist-hip ratio, glycemic control, lipid profile, and insulin sensitivity did not differ between the groups. CONCLUSION: There was no difference in outcomes between the group that only dieted and the group that also performed increased physical activity, despite a significant increase in exercise. This reinforces the importance of dietary changes in immediate blood pressure control.

A recessive variant in TFAM causes mtDNA depletion associated with primary ovarian insufficiency, seizures, intellectual disability and hearing loss.

Mitochondrial disorders are collectively common, genetically heterogeneous disorders in both pediatric and adult populations. They are caused by molecular defects in oxidative phosphorylation, failure of essential bioenergetic supply to mitochondria, and apoptosis. Here, we present three affected individuals from a consanguineous family of Pakistani origin with variable seizures and intellectual disability. Both females display primary ovarian insufficiency (POI), while the male shows abnormal sex hormone levels. We performed whole exome sequencing and identified a recessive missense variant c.694C > T, p.Arg232Cys in TFAM that segregates with disease. TFAM (mitochondrial transcription factor A) is a component of the mitochondrial replisome machinery that maintains mtDNA transcription and replication. In primary dermal fibroblasts, we show depletion of mtDNA and significantly altered mitochondrial function and morphology. Moreover, we observed reduced nucleoid numbers with significant changes in nucleoid size or shape in fibroblasts from an affected individual compared to controls. We also investigated the effect of tfam impairment in zebrafish; homozygous tfam mutants carrying an in-frame c.141_149 deletion recapitulate the mtDNA depletion and ovarian dysgenesis phenotypes observed in affected humans. Together, our genetic and functional data confirm that TFAM plays a pivotal role in gonad development and expands the repertoire of mitochondrial disease phenotypes.

The Diversity of Linear Conjugated Polyenes and Colours in Nature: Raman Spectroscopy as a Diagnostic Tool.

This review is centered on the linear conjugated polyenes, which encompasses chromatic biomolecules, such as carotenoids, polyunsaturated aldehydes and polyolefinic fatty acids. The linear extension of the conjugated double bonds in these molecules is the main feature that determines the spectroscopic properties as light-absorbing. These classes of compounds are responsible for the yellow, orange, red and purple colors which are observed in their parent flora and fauna in nature. Raman spectroscopy has been used as analytical tool for the characterization of these molecules, mainly due to the strong light scattering produced by the delocalized pi electrons in the carbon chain. In addition, conjugated polyenes are one of the main target molecular species for astrobiology, and we also present a brief discussion of the use of Raman spectroscopy as one of the main analytical tools for the detection of polyenes extra-terrestrially.

Human-modified landscapes narrow the isotopic niche of neotropical birds.

Deforestation and habitat loss resulting from land use changes are some of the utmost anthropogenic impacts that threaten tropical birds in human-modified landscapes (HMLs). The degree of these impacts on birds' diet, habitat use, and ecological niche can be measured by isotopic analysis. We investigated whether the isotopic niche width, food resources, and habitat use of bird trophic guilds differed between HMLs and natural landscapes (NLs) using stable carbon (δ13C) and nitrogen isotopes (δ15N). We analyzed feathers of 851 bird individuals from 28 landscapes in the Brazilian Atlantic Forest. We classified landscapes into two groups according to the percentage of forest cover (HMLs ≤ 30%; NLs ≥ 47%), and compared the isotopic niche width and mean values of δ13C and δ15N for each guild between landscape types. The niches of frugivores, insectivores, nectarivores, and omnivores were narrower in HMLs, whereas granivores showed the opposite pattern. In HMLs, nectarivores showed a reduction of 44% in niche width, while granivores presented an expansion of 26%. Individuals in HMLs consumed more resources from agricultural areas (C4 plants), but almost all guilds showed a preference for forest resources (C3 plants) in both landscape types, except granivores. Degraded and fragmented landscapes typically present a lower availability of habitat and food resources for many species, which was reflected by the reduction in niche width of birds in HMLs. Therefore, to protect the diversity of guilds in HMLs, landscape management strategies that offer birds more diverse habitats must be implemented in tropical regions.

From the vineyard to the cellar: new insights of Starmerella bacillaris (synonym Candida zemplinina) technological properties and genomic perspective.

A large diversity of yeasts can be involved in alcoholic fermentation; however, Starmerella bacillaris strains have gained great attention due to their relevant and particular characteristics. S. bacillaris is commonly known as an osmotolerant, acidogenic, psychrotolerant, and fructophilic yeast. Most strains of this species are high producers of glycerol and show low ethanol production rates, being highlighted as promising alternatives to the manufacture of low-alcohol beverages. The increased production of high alcohols, such as benzyl alcohol that has antifungal and antibacterial properties, highlights S. bacillaris potential as a biocontrol agent. After harvest, antifungal yeasts become part of the must microbiota and may also improve the fermentation process. Moreover, during the fermentation, S. bacillaris releases important molecules with biotechnological properties, such as mannoproteins and glutathione. Considering the potential biotechnological properties of S. bacillaris strains, this review presents an overview of recent trends concerning the application of S. bacillaris in fermented beverages. KEY POINTS: •S. bacillaris as an alternative to the production of low-alcohol beverages. •S. bacillaris strains present biocontrol potential. •Molecules released by S. bacillaris may be of great biotechnological interest.

Hip and Knee Weakness and Ankle Dorsiflexion Restriction in Individuals Following Lateral Patellar Dislocation: A Case-Control Study.

OBJECTIVE: To explore the relationship between ankle dorsiflexion range of motion (ROM) and hip and knee muscle strength between patients with a history of patellar dislocation (PD) to healthy controls. DESIGN: Case-control study. SETTING: Orthopedical specialty outpatient clinic at a tertiary hospital. PARTICIPANTS: Eighty-eight individuals were recruited; 44 individuals aged 16 years or older, of both sexes, with a history of at least one episode of atraumatic unilateral or bilateral PD requiring emergency care (14 men; 30 women; mean age 20 years) and 44 healthy (control) individuals (11 men; 33 women; mean age 21 years) matched for age, weight, and height to PD cases. INTERVENTION: Assessment of hip and knee strength and ankle dorsiflexion ROM. OUTCOME MEASURES: Ankle dorsiflexion ROM was assessed through the lunge test with a goniometer. Hip and knee muscle strength was evaluated through isometric hand-held dynamometry. Differences between healthy and control individuals were assessed using Student t Tests and Mann-Whitney U Test. RESULTS: Patellar dislocation individuals presented with a reduced ankle dorsiflexion ROM [mean difference (MD): 9 degrees; effect size (ES): 1.39; P < 0.001] and generalized hip and knee weakness (MD range: 4.74 kgf to 31.4 kgf; ES range: 0.52-2.35; P < 0.05) compared with healthy subjects. CONCLUSION: Individuals with a history of PD have reduced ankle dorsiflexion ROM and hip and knee muscle strength compared with healthy controls.

Uterine aquaporin expression is dynamically regulated by estradiol and progesterone and ovarian stimulation disrupts embryo implantation without affecting luminal closure.

The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.

Uterine Gαq/11 signaling, in a progesterone-dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse.

A nonreceptive uterus is a major cause of embryo implantation failure. This study examined the importance of the Gαq/11-coupled class of GPCRs as regulators of uterine receptivity. Mice were created lacking uterine Gαq and Gα11; as a result, signaling by all uterine Gαq/11-coupled receptors was disrupted. Reproductive profiling of the knockout females revealed that on d 4 of pregnancy, despite adequate serum progesterone (P4) levels and normal P4 receptor (PR) expression, there was no evidence of PR signaling. This resulted in the down-regulation of heart and neural crest derivatives expressed 2, Kruppel-like factor 15, and cyclin G1 and the subsequent persistent proliferation of the luminal epithelium. Aquaporin (Aqp) 11 was also potently down-regulated, whereas Aqp5/AQP5 expression persisted, resulting in the inhibition of luminal closure. Hypertrophy of the myometrial longitudinal muscle was also dramatically diminished, likely contributing to the observed implantation failure. Further analyses revealed that a major mechanism via which uterine Gαq/11 signaling induces PR signaling is through the transcriptional up-regulation of leucine-rich repeat-containing GPCR 4 (Lgr4). LGR4 was previously identified as a trigger of PR activation and signaling. Overall, this study establishes that Gαq/11 signaling, in a P4-dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse, and disruption of such signaling results in P4 resistance.-de Oliveira, V., Schaefer, J., Calder, M., Lydon, J. P., DeMayo, F. J., Bhattacharya, M., Radovick, S., Babwah, A. V. Uterine Gαq/11 signaling, in a progesterone-dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse.

Effect of Plantar Flexor Muscle Strengthening on the Gait of Children With Idiopathic Toe Walking: A Study Protocol.

PURPOSE: To evaluate the effect of plantar flexor strengthening associated with conventional physical therapy treatment in participants with idiopathic toe walking. METHODS: Thirty participants, of both sexes diagnosed with idiopathic toe walking, aged 5 and 11 years, will be recruited and randomized into 2 groups: the control group, who will undergo gait training, triceps surae muscle stretching, anterior tibial muscle strengthening, and motor sensory training, and the intervention group, who will undergo the same training as the control group and, additionally, triceps surae muscle strengthening. The intervention will be performed twice a week for 8 weeks. The participants will undergo a 3-dimensional gait kinematic analysis, passive amplitude of dorsiflexion movement, isometric dynamometry of the anterior tibial and triceps surae muscles, motor coordination, quality of life, and perception of the parents regarding the equinus gait at baseline and at the end of treatment. Quality of life will be reevaluated during a 24-week follow-up.

Prevention Is the Best Treatment: The Case for Understanding the Transition from Monoclonal Gammopathy of Undetermined Significance to Myeloma.

Multiple myeloma is an invariably fatal cancer of plasma cells. Despite tremendous advances in treatment, this malignancy remains incurable in most individuals. We postulate that strategies aimed at prevention have the potential to be more effective in preventing myeloma-related death than additional pharmaceutical strategies aimed at treating advanced disease. Here, we present a rationale for the development of prevention therapy and highlight potential target areas of study.

Use of Natural Antioxidants in the Inhibition of Cholesterol Oxidation: A Review.

Synthetic antioxidants are widely used in the food industry. However, the potential toxicity, carcinogenic effects, and possible health damage caused by the ingestion of synthetic compounds, and also consumer concern about the safety of such additives has motivated the food industry to search for natural alternatives. Natural compounds with antioxidant properties are able to retard or prevent lipid oxidation in food. Animal sources like fish, eggs, meats, and dairy products are essential foods for human health due to their lipid fraction with high contents of unsaturated compounds, such as polyunsaturated fatty acids and cholesterol. However, these unsaturated lipids when exposed to favorable factors can become oxidized, which leads to sensory and nutritional losses as well as the formation of oxidized compounds known as cholesterol oxidation products or COPs. COPs are associated with deleterious health effects, such as inflammation, cytotoxicity, atherogenesis, carcinogenesis, and alterations in cell membrane properties, as well as the development of degenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and other chronic diseases. Thus, the use of natural antioxidants can be an alternative to synthetics to prevent the formation of COPs and extend the shelf life of foods susceptible to oxidative deterioration. This review brings together information concerning the use of natural antioxidants as a strategy to control cholesterol oxidation.

Photobiomodulation therapy in the modulation of inflammatory mediators and bradykinin receptors in an experimental model of acute osteoarthritis.

The objective of this study was to evaluate the effects of photobiomodulation therapy (PBMT) on inflammatory indicators, i.e., inflammatory mediators (TNF-α and CINC-1), and pain characterized by hyperalgesia and B1 and B2 receptor activation at 6, 24, and 48 h after papain-induced osteoarthritis (OA) in rats. Fifty-four rats were subjected to hyperalgesia evaluations and then divided randomly into three groups-a control group and two groups OA and OA PBMT group by using laser parameters at wavelength (808 nm), output power (50 mW), energy per point (4 Joules), power density (1.78 W/cm2), laser beam (0.028 cm2), and energy density (144 J/cm2)-the induction of osteoarthritis was then performed with 20-µl injections of a 4 % papain solution dissolved in 10 µl of saline solution, to which 10 µl of cysteine solution (0.03 M). The statistical analysis was performed using two-way ANOVA with Bonferroni's post hoc test for comparisons between the 6, 24, and 48 h and team points within each group, and between the control, injury, and PBMT groups, and p < 0.05 was considered to indicate a significant difference. The hyperalgesia was evaluated at 6, 24, and 48 h after the injury. PBMT at a wavelength of 808 nm and doses of 4 J, administered afterward, promotes increase at the threshold of pressure stimulus at 6, 24, and 48 h after application and promote cytokine attenuation levels (TNF and CINC-1) and bradykinin receptor (B1 and B2) along the experimental period. We conclude that photobiomodulation therapy was able to promote the reduction of proinflammatory cytokines such as TNF-α and CINC-1, to reduce the gene and protein expression of the bradykinin receptor (B1 and B2), as well as increasing the stimulus response threshold of pressure in an experimental model of acute osteoarthritis.

Photobiomodulation therapy on collagen type I and III, vascular endothelial growth factor, and metalloproteinase in experimentally induced tendinopathy in aged rats.

This study investigates the effect of photobiomodulation therapy (PBMT) on collagen type I and III, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF) in experimentally induced tendinopathy in female aged rats. Tendinopathy was induced by the Achilles tendoncollagenase peritendinous. Forty-two Wistar rats (Norvegicus albinus) were used; groups consisted of 36 aged animals (18 months old; mean body weight, 517.7 ± 27.54 g) and 6 adult animals (12 weeks old; mean body weight, 266± 19.30 g). The animals were divided into three groups: control, aged tendinopathy, and aged tendinopathy PBMT; the aged groups were subdivided based on time to euthanasia: 7, 14, and 21 days. PBMT involved a gallium-arsenide-aluminum laser (Theralaser, DMC®) with active medium operating at wavelength 830 ± 10 nm, 50 mW power, 0.028 cm2 laser beam, 107 J/cm2 energy density, 1.8 W/cm2 power density, and an energy of 3 J per point. The laser was applied by direct contact with the left Achilles tendon during 60 s per point at a frequency of three times per week, until the euthanasia date (7, 14, and 21 days). VEGF, MMP-3, and MMP-9 were analyzed by immunohistochemistry, and collagen type I and III by Sirius red. PBMT increased the deposition of collagen type I and III in a gradual manner, with significant differences relative to the group aged tendonitis (p < 0.001), and in relation to VEGF (p < 0.001); decreased expression of MMP-3 and 9 were observed in group aged tendinopathy (p < 0.001). PBMT, therefore, increased the production of collagen type I and III, downregulated the expression of MMP-3 and MMP-9, and upregulated that of VEGF, with age and age-induced hormonal deficiency.

Chelerythrine inhibits the sarco/endoplasmic reticulum Ca(2+)-ATPase and results in cell Ca(2+) imbalance.

The isoquinoline alkaloid chelerythrine is described as an inhibitor of SERCA. The ATPase inhibition presented two non-competitive components, Ki1=1, 2 µM and Ki2=26 µM. Conversely, chelerythrine presented a dual effect on the p-nitrophenylphosphatase (pNPPase) of SERCA. Ca(2+)-dependent pNPPase was activated up to ∼5 µM chelerythrine with inhibition thereafter. Ca(2+)-independent pNPPase was solely inhibited. The phosphorylation of SERCA with ATP reached half-inhibition with 10 µM chelerythrine and did not parallel the decrease of ATPase activity. In contrast, chelerythrine up to 50 µM increased the phosphorylation by Pi. Cross-linking of SERCA with glutaraldehyde was counteracted by high concentrations of chelerythrine. The controlled tryptic digestion of SERCA shows that the low-affinity binding of chelerythrine evoked an E2-like pattern. Our data indicate a non-competitive inhibition of ATP hydrolysis that favors buildup of the E2-conformers of the enzyme. Chelerythrine as low as 0.5-1.5 µM resulted in an increase of intracellular Ca(2+) on cultured PBMC cells. The inhibition of SERCA and the loss of cell Ca(2+) homeostasis could in part be responsible for some described cytotoxic effects of the alkaloid. Thus, the choice of chelerythrine as a PKC-inhibitor should consider its potential cytotoxicity due to the alkaloid's effects on SERCA.