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| 2. |
- Lindberg, Frida A, et al.
(författare)
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SLC38A10 deficiency in male mice affect plasma levels of threonine and histidine
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Solute carriers belong to the biggest group of transporters in the human genome, but more knowledge is needed in order to fully understand their function and possible role as therapeutic targets. SLC38 is a family of amino acid transporters, commonly referred to as SNATs, consisting of 11 members. The tenth member, SLC38A10, is one of the least characterized members and is the focus of this study. By using a knockout mouse model, we studied the biological effects of SLC38A10 deficiency in vivo. We performed a transcriptomic analysis of whole brain and found seven differentially expressed genes in SLC38A10 deficient mice (Gm48159, Nr4a1, Tuba1c, Lrrc56, mt-Tp, Hbb-bt and Snord116/9). By measuring amino acids in plasma, we found lower levels of threonine and histidine in males, while no amino acids were altered in females, suggesting that SLC38A10-/- might affect sexes differently. Using RT-qPCR, we investigated the effect of SLC38A10 deficiency on mRNA expression of other SLC38 members, Mtor and Rps6kb1 in brain, liver, lung, muscle and kidney, but no differences were found. A relative telomere length measurement was also made, as a marker for cellular age, but no differences were found between the genotypes. We conclude that SLC38A10 might be important for keeping amino acid homeostasis in plasma, at least in males, but no major effects were seen on transcriptomic expression or telomere length in whole brain.
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| 3. |
- Gezelius, Henrik, 1977-, et al.
(författare)
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Conditional genetic labeling of the Renshaw cell population for functional studies of motor control
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The Renshaw cells were among the first interneurons to be characterized in the mammalian spinal cord. Although the basic function of recurrent inhibition to motor neurons, as well as the Renshaw cell connectivity to other neurons have been thoroughly studied, the exact functional role of the Renshaw cells in motor control is still unknown. To further characterize the role of Renshaw cells in spinal cord circuitry, we searched for candidate genes useful in the Cre-loxP system. It has been reported that the mRNA expression of nicotinic cholinergic receptor alpha 2 (Chrna2) is found in a restricted number of cells at the ventral rim in adult rat and mouse spinal cord. In our own search for genes with distinct ventral expression, we noted a similar restricted Chrna2 mRNA expression pattern in the mouse spinal cord at postnatal day (P) 11 and during development at embryonic day 14.5. Based on the fact that the gene product is a cholinergic receptor and the pattern of expression, the neurons are predicted to be Renshaw cells. The possibility that these cells were motor neurons was excluded, since Chrna2 and Vesicular acetylcholine were not co-expressed at P11. To further study this cell population, we have generated a transgenic mouse expressing Cre recombinase (Cre) under the control of the Chrna2 promoter region. To visualize the Cre-expressing cells, the Chrna2-Cre transgenic mouse were bred with a reporter mouse expressing β-galactosidase (β-gal) in the nucleus after loxP excision. As expected, spinal cord β-gal immunoreactivity was observed in a limited number of ventrally located cells in the Cre-bearing offspring. Co-labeling of β-gal with calbindin-28K, a known marker for Renshaw cells, indicated that a majority of the calbindin positive cells were also β-gal positive at the ventral rim where calbindin is specific. In addition, β-gal positive cells without observable calbindin were also detected. It is conceivable that Chrna2 is expressed in additional cells apart from Renshaw cells or that a previously unidentified Renshaw cell subpopulation does not express calbindin. Nonetheless, a mouse with Cre-activity restricted to Chrna2-expressing cells opens the possibility to functionally study a limited population of spinal cord interneurons through genetic techniques, with the ambition to explore the specific role of Renshaw cells in spinal cord circuitry and motor control.
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| 4. |
- Stafberg, Linda, et al.
(författare)
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The mRNA expression of endocannabinoid-related enzymes in rat prostate AT-1 cells following exposure to lactate and interleukin-6
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The endocannabinoid system is dysregulated in prostate cancer but the mechanisms responsible for this dysregulation are not known. We hypothesise that the dysregulation is secondary to factors in the tumour microenvironment. In this study we investigated the effects of lactic acid induced low pH and interleukin-6 (IL-6) treatment upon the expression of endocannabinoid related enzymes and the functional effects upon anandamide degradation and cell viability in Dunning R3327 rat prostate AT-1 cancer cells. Cells were exposed for 3 h at 37 °C to Krebs-Ringer-HEPES/bicarbonate buffer at either pH 7.4 or at pH 6.6 (due to the presence of 40 mM lactic acid), and to 0, 25 or 100 ng/ml of IL-6. Neither low pH (pH 6.6) nor IL-6 induced any changes in the mRNA levels of the anandamide metabolic enzymes. However, the expression of the 2- arachidonoylglycerol-synthesizing enzyme DAGLα was increased by low pH and the expression of CB2 receptor mRNA was decreased at the low pH. The DAGL inhibitor orlistat increased extracellular LDH levels after 24 h of incubation of AT-1 cells, suggesting a higher frequency of cell death. It is concluded that under the conditions used, exposure to lactate and IL-6 do not affect the expression of the anandamide metabolic enzymes in AT-1 cells, but do modify the expression of an enzyme involved in the synthesis of 2-arachidonoylglycerol.
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| 5. |
- Uusimäki, Liisa, 1959
(författare)
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Panteha Bigdeli / The link between oral care and your general health
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Dr. Panteha Bigdeli, is an innovative entrepreneur and CEO behind AuraDent. As a highly skilled and compassionate dentist, Dr. Bigdeli is dedicated to transforming smiles with the latest advancements in orthodontic care. With dual degrees in Dentistry and a Master of Science in Dental Surgery from Malmö University in Sweden, she brings a wealth of expertise to her practice. Dr. Bigdeli is deeply committed to providing top-notch patient care, with a special focus on Invisalign treatment. Recognizing the transformative potential of this cutting-edge aligner system, she has honed her skills to master the art of Invisalign, ensuring her patients receive the best possible outcomes. In her discussions, Dr. Bigdeli emphasizes the rapid technological advancements that have made dental visits more efficient and less painful. She also underscores the importance of open communication with your dentist about any fears or anxieties related to treatment. In Sweden, where dental check-ups are mandatory for children aged 3 to 18, Dr. Bigdeli expresses concern about parents who suffer from dental anxiety themselves. She advises that parents with such anxieties consider having another family member or friend accompany their child to these appointments, as parental fears can easily be transferred to the child. Dr. Bigdeli also addresses the common reasons why adults, particularly the elderly, tend to avoid regular dental check-ups. She notes that feelings of shame over poor oral care and concerns about the costs of dental visits often prevent people from seeking the care they need.
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| 6. |
- Elcadi, Guilherme H, 1966-, et al.
(författare)
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No differences in oxygenation in the forearm and shoulder of patients with work-related muscle pain and healthy subjects during a low-load sustained contraction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A frequently ascribed symptom associated to work-related muscle pain (WRMP) is muscle fatigue. Studies investigating oxygenation and hemodynamics in association to fatigue development in the muscles of patients with WRMP are sparse. Inadequate oxygen consumption and/or inadequate blood supply can influence the ability of the muscles to withstand fatigue. In this study we applied near-infrared spectroscopy (NIRS) and electromyography (EMG) to investigate oxygenation, hemodynamics and muscle activity in the extensor carpi radialis (ECR) and trapezius (TD) muscles of patients with WRMP and healthy controls. Eighteen patients with diffuse neck-shoulder-arm pain and 17 controls (matched in age and sex) were equipped with NIRS and EMG probes. After determination of maximal voluntary contraction (MVC) a sustained contraction of 15% MVC was performed with a cutoff for the maximum time of 12 min. Variables generated were StO2% and HbT from NIRS and RMS%max and MPF from EMG during the contraction. T tests and Mann-Whitney tests were used for analyzes of differences in MVC and endurance times. Full factorial repeated measures analyses of variance (ANOVA) were used to assess differences between patients and controls in NIRS and EMG parameters over time. Results showed no differences in MVC between patients and controls. We found, however, a shorter endurance time for patients compared to controls. There were no significant differences in StO2%, HbT, RMS and MPF responses during contraction between groups for the ECR. For the TD there was a group effect for StO2% with patients showing a lower level at rest and throughout the contraction. For the ECR and TD oxygenation, hemodynamics, RMS and MPF there were no straightforward differences between patients and controls that could explain the differences in endurance time. Therefore, we conclude that the shorter endurance time seen in the present study was not measurable by physiological indicators investigated in this group of patients.
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| 7. |
- Sivertsson, Ebba, et al.
(författare)
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Lowering plasma levels of protein-bound uremic toxins improves cardiac output and renal oxygenation in a rat model of chronic kidney disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Chronic kidney disease (CKD) is an increasing health problem which is closely associated with cardiac dysfunction. In CKD uremic toxins accumulate as kidney function declines. Indoxyl sulfate is a uremic toxin that induces kidney tissue hypoxia, proteinuria and kidney damage. Furthermore, high salt intake is a growing health issue worldwide. In this study, we investigated the effect of reducing plasma indoxyl sulfate in a rat model of CKD challenged with high salt intake and compared the effects to that of conventional treatment using an angiotensin converting enzyme inhibitor (ACEI). In rats, the right kidney and 2/3 of the left kidney were surgically removed (5/6 nephrectomy). Animals were fed a normal salt containing diet for four weeks and randomized to either vehicle or chronic treatment with either the oral absorbent AST-120 or the ACEI enalapril. Thereafter, kidney function was measured before and after a week of high salt intake. Cardiac output was measured at the end of the study period. A reduction of plasma levels of indoxyl sulfate by AST-120 improved cardiac output as well as urinary oxidative stress and proteinuria. ACEI reduced oxidative stress in kidney tissue and significantly improved proteinuria and the glomerular filtration rate in response to the high salt intake. Both interventions improved intrarenal oxygen availability.In conclusion, decreasing circulating levels of protein bound uremic toxins, e.g. indoxyl sulfate, improves cardiac output, reduces urinary oxidative stress and proteinuria in experimental CKD. Reduced angiotensin II signaling has direct reno-protective effects by decreasing intrarenal oxidative stress, protecting renal reserve and increasing urinary Na+ excretion during high salt intake. Both treatments had striking effects on cortical oxygen availability. A dual strategy, to reduce indoxyl sulfate and angiotensin II signaling simultaneously, could be an efficient strategy to target both cardiac and renal dysfunction in CKD, to further slow progression of disease.
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| 8. |
- Sivertsson, Ebba, 1984-, et al.
(författare)
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Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The proposed mechanisms for the development of nephropathy are many, complex and often overlapping. Although recent literature strongly supports a role of kidney hypoxia as an independent pathway to nephropathy, the evidence remains inconclusive since the role of hypoxia is difficult to differentiate from confounding factors such as hyperglycemia, hypertension and oxidative stress. By increasing kidney oxygen consumption using triiodothyronine (T3) and, thus, avoiding these confounding factors, the aim of the present study was to investigate renal hypoxia per se as a causal pathway for the development of nephropathy.Healthy Sprague-Dawley rats were treated with T3 (10 µg/kg/day) and the angiotensin II AT1-receptor antagonist candesartan (1 mg/kg in drinking water) to eliminate effects of T3-induced renin release for 7 weeks after which in vivo kidney function, oxygen metabolism and mitochondrial function were evaluated.T3 did not affect glomerular filtration rate or renal blood flow, but increased total kidney oxygen consumption resulting in cortical hypoxia. Nephropathy, demonstrated as proteinuria and albuminuria developed in T3-treated animals. Mitochondria uncoupling mediated by uncoupling protein 2 and the adenosine nucleotide transporter was demonstrated as a mechanism causing the increased kidney oxygen consumption. Importantly, blood glucose levels, mean arterial blood pressure and oxidative stress levels were not affected by T3. In conclusion, the present study provides further evidence for increased kidney oxygen consumption causing intrarenal tissue hypoxia, as a causal pathway for development of nephropathy.
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| 10. |
- Ihse, Elisabet, 1977-, et al.
(författare)
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Amyloid fibrils with fragmented ATTR may be the rule in non-Val30Met ATTR amyloidosis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one composed of only intact ATTR (type B). Patients with type A fibrils have a late age of onset and signs of cardiomyopathy, while patients with type B fibrils have an early onset and much less myocardial involvement. The present study aimed to determine if the correlation between fibril type and clinical phenotype is true for familial amyloidosis in general. Cardiac and/or adipose tissue from 48 patients carrying 21 different non-TTRV30M mutations were examined, as well as 7 non-Swedish ATTRV30M patients. Fibril type was determined with western blotting and compared to the patients´ age of onset and degree of cardiomyopathy. Non-Swedish V30M patients showed the same correlation as described for Swedish V30M patients, with fibrils of only full-length ATTR (type B) linked to less myocardial involvement. In contrast, all patients with non-V30M mutations had a fibril composition with ATTR fragments (type A). Some of these patients had onset of disease at young age. The vast majority had increased thickness of left cardiac ventricle, but a few individuals had values within normal limits. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis. It also suggests that fibrils composed of only full-length ATTR is an exception, perhaps only found among young ATTRV30M amyloidosis patients.
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