Acute effect of exercise intensity on circulating FGF-21, FSTL-1, cathepsin B, and BDNF in young men.

Background/objectives: Exercise intensity is potentially an important regulator of various exerkines secretion, but the optimal exercise intensity to increase and sustain exerkines levels, including FGF-21, FSTL-1, cathepsin B, and BDNF in humans, has not yet been fully elucidated. This study aimed to examine the circulating levels of FGF-21, FSTL-1, cathepsin B, and BDNF according to the exercise intensity. Methods: Nine young men (24.0 ± 0.4 years old) performed 4 different experimental sessions at 1-week intervals: 1) a control session (CTRL; no exercise); 2) moderate-intensity continuous exercise (MICE, 55% HRR); 3) vigorous-intensity continuous exercise (VICE, 85% HRR); and 4) high-intensity interval exercise (HIIE, 4 repetitions of a 30-s of "all out" cycling workout followed by a 4-min recovery). Blood samples were collected at 4 different time points (pre-exercise, immediately post-exercise, 30 min post-exercise, and 90 min post-exercise). Results: Serum FGF-21, FSTL-1, cathepsin B, and BDNF were higher in HIIE than in CTRL immediately post-exercise, and FSTL-1, cathepsin B, and BDNF were higher in HIIE than in MICE immediately post-exercise (P < 0.05). The AUC for FGF-21, FSTL-1, and BDNF was higher in HIIE than in CTRL, and the AUC for FGF-21 and BDNF was higher in HIIE than in MICE (P < 0.05). Furthermore, the change in blood lactate was positively correlated with the changes in all exerkines. Conclusions: This study demonstrates that acute HIIE effectively increases serum FGF-21, FSTL-1, cathepsin B, and BDNF compared to MICE. Therefore, the secretion of exerkines, including FGF-21, FSTL-1, cathepsin B, and BDNF may be exercise intensity-dependent.

Lactiplantibacillus sp. D10-2: potential bacteria for eliminating bisphenol A and reducing BpA-induced lipid accumulation.

Bisphenol A (BpA) is an endocrine-disrupting substance commonly found in plastics and resins. It is reported that BpA exposure induces lipid accumulation in humans, similar to obesogenic compounds. The main objective of this study is to investigate the removal of BpA using Lactiplantibacillus sp. D10-2, and to examine its potential for reducing BpA-induced lipid accumulation in 3T3-L1 cell line model. The heat-dried cells of Lactiplantibacillus sp. D10-2 showed 69.7% removal efficiency for initial BpA concentration of 10 µg/mL, which was 30.5% higher than the live cells. The absence of metabolites or intermediates in BpA removal studies indicates that the Lactiplantibacillus sp. D10-2 strain removed BpA by adsorption process. The hydrophobic interactions of heat-dried Lactiplantibacillus sp. D10-2 cells were observed to be higher with 33.7% compared to live cells (15.0%), suggesting a stronger ability to bind with BpA. Although the BpA binding onto Lactiplantibacillus sp. D10-2 was not affected by pH, it was confirmed that as the temperature increases, the binding ability got decreased due to mass transfer and diffusion of BpA molecules. Treatment with Lactiplantibacillus sp. D10-2 (0.1, 0.25, 0.5, 1%) reduced lipid accumulation by 61.7, 58.0, 52.7 and 60.4% in 3T3-L1 cells exposed with BpA. In addition, it was confirmed that Lactiplantibacillus sp. D10-2 treatment suppressed the protein expression levels of lipogenesis-related PPARγ and C/EBPα in 3T3-L1 cells. The results of the study suggest that the Lactiplantibacillus sp. D10-2 strain can remove BpA and reduce BpA-accelerated lipid accumulation in 3T3-L1 cells.

Evaluation of Lentilactobacillus parafarraginis A6-2 strain for aluminum removal and anti-inflammatory effects: implications for alleviating Al toxicity.

AIM: To assess the effectiveness of Lentilactobacillus parafarraginis A6-2 cell lysate for the removal of aluminum (Al), which induces neurotoxicity, and its protective effect at cellular level. METHODS AND RESULTS: The cell lysate of the selected L. parafarraginis A6-2 strain demonstrated superior Al removal compared to live or dead cells. The Al removal efficiency of L. parafarraginis A6-2 cell lysate increased with decreasing pH and increasing temperature, primarily through adsorption onto peptidoglycan. Neurotoxicity mitigation potential of L. parafarraginis A6-2 was evaluated using C6 glioma cells. C6 cells exposed with increasing concentration of Al led to elevated toxicity and inflammation, which were gradually alleviated upon treatment with L. parafarraginis A6-2. Moreover, Al-induced oxidative stress in C6 cells showed a concentration-dependent reduction upon treatment with L. parafarraginis A6-2. CONCLUSIONS: This study demonstrated that L. parafarraginis A6-2 strain, particularly in its lysate form, exhibited enhanced capability for Al removal. Furthermore, it effectively mitigated Al-induced toxicity, inflammation, and oxidative stress.

Detoxification of p-nitrophenol (PNP) using Enterococcus gallinarum JT-02 isolated from animal farm waste sludge.

Enterococcus gallinarum (JT-02) isolated and identified from the animal farm waste sludge was found to be capable of biodegrading p-nitrophenol (PNP), an organic compound used to manufacture drugs, fungicides, insecticides, dyes, and to darken leather. The intention of this study was to optimize the biodegradation by finding the optimal conditions for the specific strain through single-factor experiments. The bacterial strain was grown in Luria Bertani broth and various parameters were optimized to achieve the prime settings for the p-nitrophenol (PNP) biodegradation. The results indicated that the best setups for the biodegradation by the strain JT-02 was 100 mg/L of PNP; pH 7; 30 °C; 150 rpm in a shaker incubator and 3% (v/v) of inoculum dose. Once the optimal conditions were found, the bacteria were capable of degrading p-nitrophenol (98.21%) in 4 days. Intermediates produced during PNP biodegradation were identified using High Performance Liquid Chromatography (HPLC) analysis and the biodegradation pathway was elucidated. Phytotoxicity studies were carried out with Vigna radiata seeds to confirm the applicability and efficiency of PNP biodegradation.

Self Capacitance Mismatch Calibration Technique for Fully-Differential Touch Screen Panel Self Capacitance Sensing System.

This paper presents a fully-differential touch screen panel (TSP) self-capacitance sensing (SCS) system with a self-capacitance mismatch calibration technique. Due to the self-capacitance mismatch of TSP, the analog front-end (AFE) of the receiver (RX) circuit suffers from dynamic range degradation and gain limitations, which lead to the signal-to-noise ratio (SNR) loss for the TSP SCS system. The proposed calibration introduces the difference in input resistance and the driving amplifier's strength between the fully-differential input. Thus, the mismatch effect is efficiently relieved in terms of area and power consumption. The proposed calibration restores the SNR by 19.54 dB even under the worst self-capacitance mismatch case.

Exploring the experiences of frontline nurses caring for COVID-19 patients.

AIM: This study seeks to gain a comprehensive understanding of the experiences of frontline nurses who provided direct care for COVID-19 patients. BACKGROUND: Due to the COVID-19 pandemic, the demands on healthcare systems have been higher than before. Although previous studies have explored the experiences of frontline nurses, these experiences could vary depending on each country's social, cultural, and historical contexts. INTRODUCTION: In the midst of the global pandemic, sharing the experiences of COVID-19 frontline nurses could have implications for both nursing and nursing policies that could be applied to future pandemics. METHODS: This descriptive qualitative study comprised 14 South Korean nurses with a minimum of one month of experience working within a COVID-19 department. Individual interviews were conducted on a virtual platform, and a thematic analysis was employed. The consolidated criteria for reporting qualitative studies were used to ensure a detailed reporting of the study. RESULTS: Four themes and 12 subthemes were developed. The themes included: (1) feeling forced into a world of uncertainty; (2) providing unique care for COVID-19 patients; (3) perceiving barriers to providing quality care; and (4) seeking meaning in caring for COVID-19 patients. DISCUSSION: Nurses recognized their unique roles in caring for COVID-19 patients and sought new meanings within their profession. However, the poor work environment exacerbated the physical and emotional burden among the nurses and compromised the provision of quality care. CONCLUSION: This study highlighted the nursing policy issues that need to be improved to ensure better quality care and a stronger healthcare system. IMPLICATIONS FOR NURSING POLICY: Governmental action is essential to ensure that nurses can maintain the quality of care they have provided during COVID-19 and any future pandemics.

Isolated Avulsion Fracture of the Tibial Tuberosity in an Adult Treated with Suture-Bridge Fixation: A Rare Case and Literature Review.

Background and objectives: Isolated tibial tuberosity avulsion fractures are exceptionally uncommon among adults, with limited instances documented in published literature. Here, we describe a case of an isolated tibial tuberosity avulsion fracture in an adult that was treated successfully with the suture bridge repair technique. Patient concerns: A 65-year-old female visited the outpatient department with left knee pain after a slip and fall. Lateral radiographs and sagittal MR images of the left knee revealed the tibial tuberosity avulsion fracture, but the fracture line did not extend into the knee joint space. Surgical intervention was performed on the patient's knee using an anterior midline approach, involving open reduction and internal fixation. The avulsed tendon was grasped and pulled, and an appropriate suture location was identified. Using a suture hook, the suture was guided through the patellar tendon as near to its uppermost point of the fragment as achievable, and tied over tendon. A single suture limb from each anchor was fastened over the tibial tuberosity to the distally positioned foot print anchor, effectively anchoring the tibial tuberosity using the suture bridge technique. The patient started walking on crutches after one week and was able to walk independently with a brace after two weeks from the operation day. After three months, the patient had regained her mobility to the level prior to the injury and exhibited painless active range of motion from 0 to 130 degrees. Hardware positioning and bony union were maintained at the one-year follow-up. Conclusions: In our case, the open suture bridge fixation method for tibial tuberosity avulsion fractures produced satisfactory results. Open suture bridge fixation may be considered for isolated tibial tuberosity avulsion fractures in adults, especially when the avulsion tip is too small for screw fixation.

Is the Surface Anatomy of the Popliteal Crease Related to Lower Extremity Alignment or Knee Osseous Morphology? A Radiographic Study.

Background and objectives: The popliteal crease varies among individuals, and there has been no prior study on this aspect. We assumed that it may be associated with lower extremity alignment and osseous morphology. To demonstrate this, we conducted a radiographic analysis. Materials and Methods: The study was conducted on 121 knees of 63 patients, whose popliteal creases were well distinguished on clinical photographs. PCOA was defined as the angle between the longitudinal axis of the lower leg and the popliteal crease. Through the radiologic examinations performed, the HKA, MPTA, mLDFA, JLCA, MFCA/TEA, and PCA/TEA were measured. Pearson correlation analysis and multiple linear regression analysis were performed on the PCOA and the six radiologic measurements to analyze the relationship. Results: Pearson correlation analysis found HKA had the highest coefficient at 0.568. In multiple linear regression, only HKA was associated, excluding all other measurements. Conclusions: Popliteal crease obliquity is significantly associated with coronal plane lower extremity alignment and exhibits a stronger correlation than with underlying knee osseous morphology. If future research is conducted based on this, popliteal crease could serve as a valuable clue for predicting lower extremity alignment and the risk of osteoarthritis development.

Outcomes of total hip arthroplasty after failed free vascularized fibular grafting for osteonecrosis of the femoral head.

PURPOSE: Total hip arthroplasty (THA) after vascularized fibular grafting (VFG) is technically demanding with poorer outcomes compared to primary THA in patients with osteonecrosis of the femoral head (ONFH). The purpose of this study was to compare the outcomes of THA after VFG after removal of the graft with that of primary THA. METHODS: ONFH patients treated by VFG at a single institution were studied retrospectively. THAs after VFG performed by single arthroplasty surgeon with a single type of THA prosthesis were enrolled in the study. A control cohort of patients was created by 1:1 matching with the THA after VFG cohort according to age, gender, and American Society of Anesthesiology (ASA) score from ONFH patients treated by primary THA. Early and long-term outcomes were compared between the two groups. RESULTS: A total of 24 hips were included in the THA after VFG group and compared with 24 primary THA hips. No significant difference was noted in stem position. The THA after VFG group had increased blood loss and longer duration of operation time. There were two cases of intraoperative femur fractures in the THA after VFG group. The femoral stem of both groups were stable, with no cases of revision, and similar HHS scores at the last follow-up. CONCLUSION: THA after VFG may have similar short to midterm outcomes with primary THA after removal of the residual abutting bone graft and correct positioning of the femoral stem.

Metabolic profiling in the hypothalamus of aged mice.

Metabolic abnormalities are tightly connected to the perturbation of normal brain functions, thereby causing multiple neurodegenerative diseases. The hypothalamus is the master unit that controls the whole-body energy homeostasis. Thus, altered metabolic activity in the hypothalamus could be a crucial clue to better understand the development of metabolic disorders during aging. The current study aimed to investigate the changes in hypothalamic metabolites according to the aging process using gas chromatography-mass spectrometry. We identified that multiple metabolites and neurotransmitters were effectively reduced in the hypothalamus of aged mice. In addition, we observed increased levels of genes linked to the production and utilization of monocarboxylates in the aged hypothalamus, indicating the initiation of metabolic activity to produce alternative nutrient sources. Lastly, we found a reduced number of astrocytes in the hypothalamus of aged mice, suggesting that reduced nutrient availability in the hypothalamus might be associated with the decreased activity of astrocytes during aging. Collectively, the present study suggests that the deterioration of metabolic activities in the hypothalamus might be a primary cause and/or outcome of metabolic diseases associated with the aging process.

Improved visible-light-driven photocatalytic removal of Bisphenol A using V2O5/WO3 decorated over Zeolite: Degradation mechanism and toxicity.

WO3/Zeolite/V2O5 (TZV) composite synthesized through co-precipitation was used for the degradation of Bisphenol-A (BpA). XRD and Raman spectra were employed to ascertain the crystallinity of the composite. The pristine nature of the compound without any free particles over the zeolite surface was established through FESEM, thus, substantiating the composite character of the material. The enhancement in activity after doping with WO3 was ascertained by DRS-UV. Photocatalytic degradation studies clearly established the superiority of TZV 10 over bare V2O5. Complete BpA degradation (100%) was attained at 50 min of incubation with 0.75 g/L TZV-10 in acidic medium (pH 3) for an initial BpA concentration of 100 mg/L. HPLC-MS/MS analysis was used to decipher the degradation pathway. The catalyst was stable even after 9 cycles. Phytotoxicity studies and lake water treatment results proved the environmental efficiency of the synthesized material.

Insufficient respiratory hazard identification in the safety data sheets for cleaning and disinfection products used in healthcare organisations across England and Wales.

BACKGROUND: Exposure to cleaning and disinfection products has been associated with respiratory disorders such as asthma in cleaning and healthcare workers. Safety data sheets (SDSs) provide information on hazardous chemicals that are present in products to help users with risk assessment and implement appropriate control measures. However, they have potential limitations in identifying respiratory hazards due to a lack of regulatory test methods for respiratory sensitisation and irritation of chemicals. METHODS: SDSs were first used to identify chemicals on the database as respiratory sensitisers and irritants. A quantitative structure-activity relationship (QSAR) model and an asthmagen list established by the Association of Occupational and Environmental Clinics (AOEC) were used to identify potential respiratory sensitisers and irritants (by the AOEC list only) in the cleaning and disinfection products. RESULTS: From a total of 459 cleaning and disinfection products used in healthcare organisations across England and Wales, 35 respiratory sensitisers not labelled as such on the SDS were identified by QSAR or AOEC. Only 2% of cleaning and disinfection products contained at least one respiratory sensitiser as identified by their SDSs; this was increased to 37.7% of products when the QSAR or the AOEC list was used. CONCLUSIONS: A significantly higher proportion of cleaning products contain respiratory hazardous chemicals, particularly respiratory sensitisers than would be expected from the information provided by SDSs alone. Cleaners and healthcare workers may, therefore, be insufficiently protected.

Development of a discharge education program using the teach-back method for heart failure patients.

BACKGROUND: Heart failure (HF) patients have difficulties in self-management after discharge. This study aimed to develop a discharge education program for HF patients using the teach-back method (TBM). METHODS: As a methodological study to develop a program, we applied the analysis, design, development, implementation, and evaluation (ADDIE) model comprised of (1) analysis using EMR data, systematic review, and focus group interviews, (2) design and development of a program draft, (3) tests of program validity using 15 experts, 10 nurses, and 10 patients, and (4) development of the final program. The content validity index (CVI), and understandability and actionability of the educational material were used. RESULTS: The discharge education program provides definitions and information about medication, symptom/weight/diet management, physical activity, and other precautions. The educational method uses TBM. The overall CVI for the program was 0.96, and all item CVIs were greater than 0.8. The understandability and actionability were 90.2 and 91.3 % in patients, and 94.6 and 86.8 % in nurses. The contents and methods of the program were appropriate for patients and providers. CONCLUSIONS: We expect the discharge education program using TBM to enhance self-management among HF patients. The process we used to develop this program could guide researchers and clinical practice.

The Potential Role of Irisin in Vascular Function and Atherosclerosis: A Review.

Exercise is an effective intervention for both the prevention and the treatment of obesity and insulin resistance because skeletal muscle secretes many bioactive proteins that contribute to the beneficial effect of exercise. It has been revealed that irisin plays an important role in metabolic homeostasis and both acute and chronic exercises increase circulating irisin in experimental animal models and in humans. Although previous studies have reported that the irisin-related signaling mechanism may play a beneficial role in the treatment of metabolic diseases including obesity, metabolic syndrome, insulin resistance, and diabetes mellitus, studies on whether irisin plays a key role in vascular function and vascular complications are still insufficient. Therefore, the current review aims to summarize the accumulating evidence showing the potential role of irisin, especially in vascular reactivity and vascular abnormalities such as atherosclerosis.

Characteristics of medial condyle sagittal fracture of distal femur involving intercondylar notch in geriatric patients.

INTRODUCTION: Unicondylar femoral fractures are uncommon injuries, known to occur primarily in young people, with high energy trauma. However, according to our experiences, unicondylar femoral fractures in geriatric patients generally involved the medial femoral condyle, unlike previously reported. In addition, the fractures of medial femoral condyle (FMFC) showed a characteristic fracture pattern. To date, there has been no published article focusing on the FMFC in geriatric patients. Thus, the aim of this study was to determine the characteristics of FMFC in geriatric patients and to present their outcomes. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 13 patients over age of 65 who underwent surgery for FMFC (AO-OTA 33B2). Of the 13, 10 patients were treated with Tomofix medial distal femoral plate (MDF) (Synthes GmbH, Switzerland) and additional screws fixation; the other three were treated with screw fixation and cast application. RESULTS: The mean age of patients was 76.8 years, and 10 patients were females. The fracture was due to low-energy trauma in all of the cases. Eight patients had medial knee osteoarthritis, and 2 patients were on osteoporosis treatment. A characteristic fracture pattern was observed. The fracture line extended from the lateral aspect of the intercondylar notch to the posteromedial column of the distal femur, with a characteristic medial beak. All fractures belonged to AO classification 33B2.1; there were no cases of AO classification 33B2.2 or 33B2.3. The postoperative joint function was graded according to the Kolmert functional criteria: ten cases were excellent, one case was good, one case was fair, and one case was poor. CONCLUSION: FMFC caused by low-energy trauma in geriatric patients tend to have a characteristic pattern. We believe that anatomic reduction and firm fixation with Tomofix MDF plate and cannulated screw for low-energy trauma FMFC in geriatric patients would yield good outcomes.

The relationship between arterial stiffness and maximal oxygen consumption in healthy young adults.

OBJECTIVE: Arterial stiffness is associated with an increased risk of cardiovascular diseases in various populations. There was little research on the relationship between arterial stiffness and maximal aerobic capacity (VO2max) in healthy young adults. The aim of this study was to investigate the relationship between VO2max and arterial stiffness in young adults. METHODS: The subjects were 13 men and 10 women with mean age of 22.9 ±â€¯0.7, 23.6 ±â€¯0.4 years, respectively. Height, weight, body mass index, body fat (%), waist to hip ratio, total/high density lipoprotein (HDL)/low density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, blood pressure, heart rate, glycated hemoglobin and blood lactate were measured. In addition, peripheral arterial stiffness was assessed by measuring brachial-ankle pulse wave velocity (baPWV) and VO2max was determined using graded exercise test. RESULTS: VO2max had no significant correlation with baPWV (r = 0.2, p = 0.2). Total cholesterol correlated significantly to variables such as HDL (r = 0.6, p = 0.0015) and LDL cholesterol (r = -0.6, p = 0.0018). VO2max had a significant association with triglyceride (r = -0.5, p = 0.0033). CONCLUSIONS: This study suggests that there is no relationship between arterial stiffness and aerobic capacity in healthy young adults.

Posterior locked lateral compression injury of the pelvis in geriatric patients: an infrequent and specific variant of the fragility fracture of pelvis.

INTRODUCTION: Posterior locked lateral compression injury (PLLCI) of the pelvic ring is an infrequent variant of lateral compression injury, a condition described in only eight reported cases since 2000. Lateral compression injury usually results from high-energy trauma and is characterized by locking between the medially translated fractured ilium and the anterior border of the sacrum, regardless of whether the fractured ilium involves the sacroiliac joint. However, in our experience, lateral compression injury can also result from low-energy trauma as a manifestation of pelvic fragility fracture. The aim of the present study was to describe this rare form of PLLCI in a case series of geriatric patients. METHODOLOGY: A retrospective analysis of consecutive patients with pelvic ring injuries who were admitted to our hospital from January 2008 to April 2015 identified seven geriatric patients (1 male and 6 females; median age 81 years) with a form of PLLCI. RESULTS: All injuries were due to falls from a standing position onto the ground. All seven cases demonstrated characteristics of a locking fractured ilium over the anterior border of the sacrum on axial computed tomography images, but were not detected on plain radiographs. All underwent follow-up at 1 year or later with improved mean visual analogue scale scores (range 0-3). Regarding Koval walking ability scores, patients who underwent pelvic brim plating with anterior external fixation were more likely to regain their pre-injury walking ability than patients who only underwent anterior external fixation or conservative treatment. CONCLUSION: Geriatric patients can experience PLCCIs of the pelvis due to low-energy trauma. These fractures have different characteristics from those associated with severe injuries due to high-energy trauma, and they comprise an infrequent form of Rommens fragility fracture of the pelvis (type IIIa). In these cases, appropriate surgical management that includes sacroiliac plating combined with anterior external fixation can yield good outcomes.

Clinical and radiologic outcomes of arthroscopic suture bridge repair for the greater tuberosity fractures of the proximal humerus.

PURPOSE: To report the clinical and radiological outcomes of arthroscopic suture bridge repair for the GT fractures of the shoulder joint. METHODS: From March 2008 to July 2013, we performed arthroscopic suture bridge repair of the GT fractures displaced more than 5 mm superiorly or posteriorly, but less than 2 cm in 40 cases [20 men, 20 women; mean age, 56 (27-80) years] with the average 32 (24-48) months follow-up. At the final follow-up, clinical (ASES, UCLA, SST, KSS score and range of motions) and radiological outcomes using post-operative MRI or CT scan were evaluated. Associated injuries occurred in 21 cases (52.5%): 8 rotator cuff tears; 7 SLAP lesions; 3 glenoid rim fractures; 3 Bankart lesions; 5 biceps tendon tears; 1 partial subscapularis tear; 1 combined subscapularis and biceps tendon tear, and 1 brachial plexus injury. RESULTS: At the final follow-up, the mean VAS score improved from 7 to 1; ASES, to 92; UCLA, to 32; KSS, to 90; and SST, to 10. Mean forward flexion, abduction, external rotation at the side, and internal rotation at the back were improved to 157°, 157°, 37° and T11, respectively. Mean residual superior and posterior displacement of the fracture was 0 (range -5 to 3.3) mm and 0.1 (-5.5 to 3.2) mm, respectively, compared to pre-operative displacement of 4.9 (0-14) mm and 4.5 (0-20) mm, respectively (p < 0.001). Complications included anchor protrusion in five cases. CONCLUSION: Arthroscopic suture bridge repair was useful for the treatment of displaced GT fractures with or without comminution and the management of the combined lesions. At the final follow-up, meaningful remodeling of the GT fracture and satisfactory clinical outcomes could be achieved.

Adiponectin Receptor Agonist, AdipoRon, Causes Vasorelaxation Predominantly Via a Direct Smooth Muscle Action.

OBJECTIVE: AdipoRon, an adiponectin receptor agonist, was recently proposed for treating insulin resistance and hyperglycemia. As adiponectin is vasoprotective via NO-mediated signaling, it was hypothesized that adipoRon similarly exerts potentially beneficial vasodilator effects. We therefore examined if adipoRon induces vasorelaxation and via what contributing mechanisms. METHODS: Vascular function was assessed in skeletal muscle arteries from rats and cerebral/coronary arteries from mice using pressure and wire myography. RESULTS: Using qPCR, mRNA for adiponectin receptors was demonstrated in skeletal muscle, cerebral and coronary arteries. AdipoRon-caused vasorelaxation was not abolished by compound C (10 µM; AMPK inhibitor). Inhibition of endothelium-dependent relaxation with combinations of l-NAME/indomethacin/apamin/TRAM-34 only slightly reduced adipoRon-mediated vasorelaxation in cerebral and coronary arteries. EC-denuded cremaster arteries showed similar relaxant responses to adipoRon as in intact vessels, suggesting adipoRon directly impacts VSMCs. K(+) currents measured in VSMCs isolated from mouse basilar and LAD arteries were not altered by adiopRon. In cremaster arteries, adipoRon induced vasorelaxation without a marked decrease in VSMC [Ca(2+)]i . Adiponectin, itself, caused vasodilation in intact cremaster arteries while failing to cause significant dilation in EC-denuded arteries, consistent with endothelium dependency of adiponectin. CONCLUSIONS: AdipoRon exerts vasodilation by mechanisms distinct to adiponectin. The dominant mechanism for adipoRon-induced vasorelaxation occurs independently of endothelium-dependent relaxing factors, AMPK activation, K(+) efflux-mediated hyperpolarization and reductions in cytosolic [Ca(2+)]i .

Heterogeneity in Kv7 channel function in the cerebral and coronary circulation.

OBJECTIVES: Kv7 channels are considered important regulators of vascular smooth muscle contractility. The present study aimed to examine the hypotheses that (i) Kv7 channels are present in mouse cerebral and coronary arteries and regulate vascular reactivity and (ii) regional differences exist in the activity of these channels. METHODS AND RESULTS: PCR confirmed that basilar, Circle of Willis and LAD arteries express predominantly Kv7.1 and 7.4. Western blot analysis, however, showed greater Kv7.4 protein levels in the cerebral vessels. Relaxation to the Kv7 channel activator, retigabine (1-50 µM) was significantly greater in the basilar artery compared to the LAD artery. Similarly, the Kv7 channel inhibitor, linopirdine (10 µM) caused a stronger contraction of the basilar artery. Furthermore, pre-incubation with linopirdine reduced forskolin (cAMP activator)-induced vasorelaxation in basilar while not altering forskolin-induced vasorelaxation of the LAD, suggesting that Kv7 channels play a more prominent role in the cerebral than in the coronary circulation. Consistent with the vessel data, whole cell Kv7 currents in cerebral VSMCs were potentiated by retigabine and inhibited by linopirdine, while these responses were blunted in coronary VSMCs. CONCLUSIONS: This study provides evidence that mouse Kv7 channels may contribute differently to regulating the functional properties of cerebral and coronary arteries. Such heterogeneity has important implications for developing novel therapeutics for cardiovascular dysfunction.