| 1. |
- Ahlgren, Åsa Rydén, et al.
(författare)
-
Response of the carotid artery longitudinal motion to submaximal physical activity in healthy humans-Marked changes already at low workload
- 2023
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 11:2
-
Tidskriftsartikel (refereegranskat)abstract
- The longitudinal motion of the arterial wall, that is, the displacement of the arterial wall along the artery, parallel to blood flow, is still largely unexplored. The magnitude and nature of putative changes in longitudinal motion of the arterial wall in response to physical activity in humans remain unknown. The aim of this study was therefore to study the longitudinal motion of the carotid artery wall during physical activity in healthy humans. Using in-house developed non-invasive ultrasonic methods, the longitudinal motion of the intima-media complex and the diameter changes of the right common carotid artery (CCA) in 40 healthy volunteers (20 volunteers aged 22-35 years; 20 volunteers aged 55-68 years) were assessed at rest and during submaximal supine bicycle exercise. In a subset of the subjects (n = 18) also intramural shear strain were analyzed. The longitudinal motion of the intima-media complex underwent marked changes in response to physical activity, already at low workload; with most evident a marked increase of the first antegrade displacement (p < 0.001) in early systole. Likewise, the corresponding shear strain also increased significantly (p = 0.004). The increase in longitudinal motion showed significant correlation to increase in blood pressure, but not to blood flow velocity or wall shear stress. In conclusion, physical activity markedly influences the longitudinal motion of the carotid artery wall in healthy humans already at low load. A possible "cushioning" function as well as possible implications for the function of the vasa vasorum, endothelium, and smooth muscle cells and extracellular matrix of the media, are discussed.
|
|
| 2. |
- Bakker, G. J., et al.
(författare)
-
Oral vancomycin treatment does not alter markers of postprandial inflammation in lean and obese subjects
- 2019
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 7:16
-
Tidskriftsartikel (refereegranskat)abstract
- Intake of a high-fat meal induces a systemic inflammatory response in the postprandial which is augmented in obese subjects. However, the underlying mechanisms of this response have not been fully elucidated. We aimed to assess the effect of gut microbiota modulation on postprandial inflammatory response in lean and obese subjects. Ten lean and ten obese subjects with metabolic syndrome received oral vancomycin 500 mg four times per day for 7 days. Oral high-fat meal tests (50 g fat/m(2) body surface area) were performed before and after vancomycin intervention. Gut microbiota composition, leukocyte counts, plasma lipopolysaccharides (LPS), LPS-binding protein (LBP), IL-6 and MCP-1 concentrations and monocyte CCR2 and cytokine expression were determined before and after the high-fat meal. Oral vancomycin treatment resulted in profound changes in gut microbiota composition and significantly decreased bacterial diversity in both groups (phylogenetic diversity pre- versus post-intervention: lean, 56.9 +/- 7.8 vs. 21.4 +/- 6.6, P < 0.001; obese, 53.9 +/- 7.8 vs. 21.0 +/- 5.9, P < 0.001). After intervention, fasting plasma LPS significantly increased (lean, median [IQR] 0.81 [0.63-1.45] EU/mL vs. 2.23 [1.33-3.83] EU/mL, P = 0.017; obese, median [IQR] 0.76 [0.45-1.03] EU/mL vs. 1.44 [1.11-4.24], P = 0.014). However, postprandial increases in leukocytes and plasma LPS were unaffected by vancomycin in both groups. Moreover, we found no changes in plasma LBP, IL-6 and MCP-1 or in monocyte CCR2 expression. Despite major vancomycin-induced disruption of the gut microbiota and increased fasting plasma LPS, the postprandial inflammatory phenotype in lean and obese subjects was unaffected in this study.
|
|
| 3. |
- Bhattachariya, Anirban, et al.
(författare)
-
PYK2 selectively mediates signals for growth versus differentiation in response to stretch of spontaneously active vascular smooth muscle.
- 2014
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 2:7
-
Tidskriftsartikel (refereegranskat)abstract
- Stretch of vascular smooth muscle stimulates growth and proliferation as well as contraction and expression of contractile/cytoskeletal proteins, all of which are also regulated by calcium-dependent signals. We studied the role of the calcium- and integrin-activated proline-rich tyrosine kinase 2 (PYK2) in stretch-induced responses of the rat portal vein loaded by a hanging weight ex vivo. PYK2 phosphorylation at Tyr-402 was increased both by a 10-min stretch and by organ culture with load over several days. Protein and DNA synthesis were reduced by the novel PYK2 inhibitor PF-4594755 (0.5-1 μmol/L), while still sensitive to stretch. In 3-day organ culture, PF-4594755 caused maintained myogenic spontaneous activity but did not affect contraction in response to high-K(+) (60 mmol/L) or to α1-adrenergic stimulation by cirazoline. Basal and stretch-induced PYK2 phosphorylation in culture were inhibited by PF-4594755, closely mimicking inhibition of non-voltage-dependent calcium influx by 2-APB (30 μmol/L). In contrast, the L-type calcium channel blocker, nifedipine (1 μmol/L) eliminated stretch-induced but not basal PYK2 phosphorylation. Stretch-induced Akt and ERK1/2 phosphorylation was eliminated by PF-4594755. PYK2 inhibition had no effect on mRNA expression of several smooth muscle markers, and stretch-sensitive SM22α synthesis was preserved. Culture of portal vein with the Ang II inhibitor losartan (1 μmol/L) eliminated stretch sensitivity of PYK2 and Akt phosphorylation, but did not affect mRNA expression of smooth muscle markers. The results suggest that PYK2 signaling functionally distinguishes effects of voltage- and non-voltage-dependent calcium influx. A small-molecule inhibitor of PYK2 reduces growth and DNA synthesis but does not affect contractile differentiation of vascular smooth muscle.
|
|
| 4. |
|
|
| 5. |
- Boon, Hanneke, 1981-, et al.
(författare)
-
MicroRNA-208b progressively declines after spinal cord injury in humans and is inversely related to myostatin expression
- 2015
-
Ingår i: Physiological Reports. - Chichester : John Wiley & Sons. - 2051-817X. ; 3:11
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of long‐term physical inactivity on the expression of microRNAs involved in the regulation of skeletal muscle mass in humans are largely unknown. MicroRNAs are short, noncoding RNAs that fine‐tune target expression through mRNA degradation or by inhibiting protein translation. Intronic to the slow, type I, muscle fiber type genes MYH7 and MYH7b, microRNA‐208b and microRNA‐499‐5p are thought to fine‐tune the expression of genes important for muscle growth, such as myostatin. Spinal cord injured humans are characterized by both skeletal muscle atrophy and transformation toward fast‐twitch, type II fibers. We determined the expression of microRNA‐208b, microRNA‐499‐5p, and myostatin in human skeletal muscle after complete cervical spinal cord injury. We also determined whether these microRNAs altered myostatin expression in rodent skeletal muscle. A progressive decline in skeletal muscle microRNA‐208b and microRNA‐499‐5p expression occurred in humans during the first year after spinal cord injury and with long‐standing spinal cord injury. Expression of myostatin was inversely correlated with microRNA‐208b and microRNA‐499‐5p in human skeletal muscle after spinal cord injury. Overexpression of microRNA‐208b in intact mouse skeletal muscle decreased myostatin expression, whereas microRNA‐499‐5p was without effect. In conclusion, we provide evidence for an inverse relationship between expression of microRNA‐208b and its previously validated target myostatin in humans with severe skeletal muscle atrophy. Moreover, we provide direct evidence that microRNA‐208b overexpression decreases myostatin gene expression in intact rodent muscle. Our results implicate that microRNA‐208b modulates myostatin expression and this may play a role in the regulation of skeletal muscle mass following spinal cord injury. © 2015 The Authors
|
|
| 6. |
- Cardinale, Daniele A, et al.
(författare)
-
Reliability of maximal mitochondrial oxidative phosphorylation in permeabilized fibers from the vastus lateralis employing high-resolution respirometry.
- 2018
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:4
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose was to assess the impact of various factors on methodological errors associated with measurement of maximal oxidative phosphorylation (OXPHOS) in human skeletal muscle determined by high-resolution respirometry in saponin-permeabilized fibers. Biopsies were collected from 25 men to assess differences in OXPHOS between two muscle bundles and to assess the correlation between OXPHOS and the wet weight of the muscle bundle. Biopsies from left and right thighs of another five subjects were collected on two occasions to compare limbs and time-points. A single muscle specimen was used to assess effects of the anesthetic carbocaine and the influence of technician. The difference in OXPHOS between two fiber-bundles from the same biopsy exhibited a standard error of measurement (SEM) of 10.5 pmol · s-1 · mg-1 and a coefficient of variation (CV) of 15.2%. The differences between left and right thighs and between two different time-points had SEMs of 9.4 and 15.2 pmol · s-1 · mg-1 and CVs of 23.9% and 33.1%, respectively. The average (±SD) values obtained by two technicians monitoring different bundles of fibers from the same biopsy were 31.3 ± 7.1 and 26.3 ± 8.1 pmol · s-1 · mg-1 . The time that elapsed after collection of the biopsy (up to a least 5 h in preservation medium), wet weight of the bundle (from 0.5 to 4.5 mg) and presence of an anesthetic did not influence OXPHOS. The major source of variation in OXPHOS measurements is the sample preparation. The thigh involved, time-point of collection, size of fiber bundles, and time that elapsed after biopsy had minor or no effect.
|
|
| 7. |
- Carlén, Anna, 1985-, et al.
(författare)
-
ST/HR variables in firefighter exercise ECG : relation to ischemic heart disease
- 2019
-
Ingår i: Physiological Reports. - : John Wiley & Sons. - 2051-817X. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- Exercise electrocardiography (ExECG) is regularly performed by Swedish firefighters by law. Heart rate-corrected analysis of ST segment variables (ST/HR) has shown improved prediction of ischemic heart disease (IHD) compared to ST depression alone. This has not previously been extensively studied in asymptomatic persons with a low probability of IHD. We therefore evaluated the predictive performance of ST/HR analysis in firefighter ExECG. ExECG was studied in 521 male firefighters. During 8.4 ± 2.1 years, 2.3% (n = 12) were verified with IHD by catheterization or myocardial scintigraphy (age 51.5 ± 5.5 years) and were compared with firefighters without imaging proof of IHD (44.2 ± 10.1 years). The predictive value of ST depression, ST/HR index, ST/HR slope, and area and rotation of the ST/HR loop was calculated as age-adjusted odds ratios (OR), in 10 ECG leads. Predictive accuracy was analyzed with receiver operating characteristics (ROC) analysis. ST/HR index ≤-1.6 μV/bpm and ST/HR slope ≤-2.4 μV/bpm were associated with increased IHD risk in three individual leads (all OR > 1.0, P < 0.05). ST/HR loop area lower than the fifth percentile of non-IHD subjects indicated IHD risk in V4, V5, aVF, II, and -aVR (P < 0.05). ST depression ≤-0.1 mV was associated with IHD only in V4 (OR, 9.6, CI, 2.3-40.0). ROC analysis of each of these variables yielded areas under the curve of 0.72 or lower for all variables and leads. Clockwise-rotated ST/HR loops was associated with increased risk in most leads compared to counterclockwise rotation. The limited clinical value of ExECG in low-risk populations was emphasized, but if performed, ST/HR analysis should probably be given more importance.
|
|
| 8. |
- Casselbrant, Anna, 1970, et al.
(författare)
-
Asymmetric mucosal structure, mesenteric versus antimesenteric, in mouse, rat, and human small intestines
- 2022
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 10:24
-
Tidskriftsartikel (refereegranskat)abstract
- The morphology of the small intestinal mucosa is reflected by the degree of stimuli. Previous studies have come to different conclusion about whether the mucosa is equally symmetrical. The aim of the study is to investigate whether there are structural differences in the mesenteric versus antimesenteric mucosa in mice, rats, and humans. Jejunal biopsies from mice and rats were saved. Samples from human small intestine were obtained from patients undergoing Roux-en-Y gastric bypass surgery. Fixed samples were used to morphologically evaluate villus height and enlargement factor due to villi. The number of goblet cells, mast cells, enteroendocrine cells, and Paneth cells were histologically analyzed in the villus structure. Cell turnover was analyzed by Ki-67 staining. There was a significant increased villi height and villus enlargement factor antimesenterically in mice, rats, and human small intestines. The distribution of goblet cells, mast cells, and Paneth cells were equal while the number of enteroendocrine cells was increased antimesenteric in the human samples. The crypt mitotic activity was almost 20% higher in the antimesenteric part of jejunum. In summary we found longer villi, greater surface enlargement, and increased number of enteroendocrine cells as well as increased cell turnover antimesenterically. These differences may be of importance in understanding normal gastrointestinal physiology in health and disease.
|
|
| 9. |
- Chaillou, Thomas, 1985-, et al.
(författare)
-
Docetaxel does not impair skeletal muscle force production in a murine model of cancer chemotherapy
- 2017
-
Ingår i: Physiological Reports. - : American Physiological Society. - 2051-817X. ; 5:11
-
Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy drugs such as docetaxel are commonly used to treat cancer. Cancer patients treated with chemotherapy experience decreased physical fitness, muscle weakness and fatigue. To date, it is unclear whether these symptoms result only from cancer-derived factors or from the combination of cancer disease and cancer treatments, such as chemotherapy. In this study, we aimed at determining the impact of chemotherapy per se on force production of hind limb muscles from healthy mice treated with docetaxel. We hypothesized that docetaxel will decrease maximal force, exacerbate the force decline during repeated contractions and impair recovery after fatiguing stimulations. We examined the function of soleus and extensor digitorum longus (EDL) muscles 24h and 72h after a single injection of docetaxel (acute treatment), and 7days after the third weekly injection of docetaxel (repeated treatment). Docetaxel was administrated by intravenous injection (20mg/kg) in female FVB/NRj mice and control mice were injected with saline solution. Our results show that neither acute nor repeated docetaxel treatment significantly alters force production during maximal contractions, repeated contractions or recovery. Only a tendency to decreased peak specific force was observed in soleus muscles 24h after a single injection of docetaxel (-17%, P=0.13). In conclusion, docetaxel administered intravenously does not impair force production in hind limb muscles from healthy mice. It remains to be clarified whether docetaxel, or other chemotherapy drugs, affect muscle function in subjects with cancer and whether the side effects associated with chemotherapy (neurotoxicity, central fatigue, decreased physical activity, etc.) are responsible for the experienced muscle weakness and fatigue.
|
|
| 10. |
- Dahlberg, Pia, et al.
(författare)
-
Accelerated QT adaptation following atropine-induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis.
- 2022
-
Ingår i: Physiological reports. - : Wiley. - 2051-817X. ; 10:21
-
Tidskriftsartikel (refereegranskat)abstract
- Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss-of-function mutations affecting the repolarizing potassium channel current IKs , presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04mg/kg body weight) for 30s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine-induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p<0.001), QT adaptation was on average 25% faster in LQT1 patients (measured as the time constant τ for the mono-exponential function and the time for 90% of ΔQT; p<0.01); however, there was some overlap between the groups, possibly a beta-blocker effect. The shorter QT adaptation time to atropine-induced HR increase in LQT1 patients on the group level corroborates the importance of IKs in QT adaptation hysteresis in humans and shows that LQT1 patients have a disturbed ultra-rapid cardiac memory. On the individual level, the QT adaptation time possibly reflects the effect-size of the loss-of-function mutation, but its clinical implications need to be shown.
|
|
