MaxiK channel partners: physiological impact

The basic functional unit of the large-conductance, voltage- and Ca²⁺-activated K⁺ (MaxiK, BK, BK_Ca) channel is a tetramer of the pore-forming α-subunit (MaxiKα) encoded by a single gene, Slo , holding multiple alternative exons. Depending on the tissue, MaxiKα can associate with modulatory β-subunits (β1–β4) increasing its functional diversity. As MaxiK senses and regulates membrane voltage and intracellular Ca²⁺, it links cell excitability with cell signalling and metabolism. Thus, MaxiK is a key regulator of vital body functions, like blood flow, uresis, immunity and neurotransmission. Epilepsy with paroxysmal dyskinesia syndrome has been recognized as a MaxiKα-related disorder caused by a gain-of-function C-terminus mutation. This channel region is also emerging as a key recognition module containing sequences for MaxiKα interaction with its surrounding signalling partners, and its targeting to cell-specific microdomains. The growing list of interacting proteins highlights the possibility that associations with the C-terminus of MaxiKα are dynamic and depending on each cellular environment. We speculate that the molecular multiplicity of the C-terminus (and intracellular loops) dictated by alternative exons may modulate or create additional interacting sites in a tissue-specific manner. A challenge is the dissection of MaxiK macromolecular signalling complexes in different tissues and their temporal association/dissociation according to the stimulus.     

Methoxyethylmercury nephrotoxicity: effects on enzymuria and kidney function

The fungicide, methoxyethylmercury chloride, was given in a saline solution to four groups of Sprague-Dawley C D rats (5 , 5 ) as a single injection (IP) of 0, 0.5, 1.0, and 2.0 mg Hg/kg. In a three-day period, no changes were observed in urine collected every 24 h from rats given 0 or 0.5 mg Hg/kg; 1 mg Hg/kg induced only a transient increase of urine gamma glutamyl transferase (x 4) and alkaline phosphatase (x 2.5) on the day 2; 2.0 mg Hg/kg caused an early increase of enzymuria (day 1 and day 2) and a decrease of Na⁺, Cl^–, K⁺, urea, and creatinin excretion. Urine enzymes and total mercury excretion were higher in males. These time-related variations of enzymuria, compared to previous results with Hg Cl₂, could reflect the existence of metabolites more toxic than the native compound.     

The effect of core stability and general exercise on abdominal muscle thickness in non-specific chronic low back pain using ultrasound imaging

Background: There is a controversy regarding whether core stability exercise (CSE) is more effective than general exercise (GE) for chronic LBP. To compare different exercises regarding their effect on improving back strength and stability, performance of abdominal muscles is a useful index. Ultrasound imaging for measuring muscle thickness could be used to assess muscle performance. Objective: The aim of this study was to compare CSE and GE in chronic LBP using ultrasound imaging for measurement of thickness of the deep stabilizing and main global trunk muscles in non-specific chronic LBP. Methods: Each program included 16 training sessions three times a week. Using ultrasound imaging, four transabdominal muscle thickness were measured before and after the intervention. Disability and pain were measured as secondary outcomes. Results: After the intervention on participants (n = 43), a significant increase in muscle thickness (hypertrophy) was seen only in right and left rectus abdominis in the GE group, but significant difference to the CSE group was only on the right side. Disability and pain reduced within the groups without a significant difference in the change between them. Conclusions: The present results provided evidence that only GE increased right and left rectus muscle thickness. The only significant difference between CSE and GE groups was the right rectus thickness. As rectus is a global muscle, the effect of GE on strength improvement (one side stronger than the other) may have a negative effect on motor control of lumbopelvic muscles and possibly increase the risk of back pain occurring or becoming worse, though this was not observed in the present study.     

The influence of laser frequency and groove distance on cell adhesion,cell viability,and antibacterial characteristics of Ti-6Al-4V dental implants treated by modern fiber engraving laser

ObjectiveMicro-nano scale surface modification of Ti-6Al-4V was investigated through the fascinated modern fiber engraving laser method. The process was performed at a high laser speed of 2000 mm/s, under different laser frequencies (20–160 kHz) and groove distances (0.5–50 μm).MethodsTopographic evaluations such as Atomic Force Microscopy (AFM) and Field Emission Scanning Electron Microscopy (FE-SEM) were used to identify the quality and regularity of patterns. The proliferation of human osteoblast-like osteosarcoma cells (MG63) was analyzed by MTT assay for up to 72 h. Also, the plate counting method was used to quantify the viability potential of the modified surface against Escherichia coli bacteria.ResultsThe cellular viability of the sample modified at the laser frequency of 20 kHz and grooving distance of 50 μm increased up to 35 and 10% compared to the non-treated and control samples, respectively. In the case of the surface modification at lower grooving distances range between 0.5–50 μm, the maximum laser frequency (160 kHz) applied leads to lower pulse’s energies and less bacterial adhesion. Otherwise, at groove distances more than 50 μm, the minimum laser frequency (20 kHz) applied reduces the laser pulse overlaps, increases the cell adhesion and antibacterial properties.SignificanceSurface modification by the fiber engraving laser process significantly enhances the cell adhesion on the surface. As a result of such roughness and cell adhesion enhancement, the surface toxicity feature diminished, and its antibacterial properties improved.     

Genistein, a soy phytoestrogen, reverses severe pulmonary hypertension and prevents right heart failure in rats

Pretreatment with a phytoestrogen genistein has been shown to attenuate the development of pulmonary hypertension (PH). Because PH is not always diagnosed early, we examined whether genistein could also reverse preexisting established PH and prevent associated right heart failure (RHF). PH was induced in male rats by 60 mg/kg of monocrotaline. After 21 days, when PH was well established, rats received daily injection of genistein (1 mg/kg per day) for 10 days or were left untreated to develop RHF by day 30. Effects of genistein on human pulmonary artery smooth muscle cell and endothelial cell proliferation and neonatal rat ventricular myocyte hypertrophy were assessed in vitro. Severe PH was evident 21 days after monocrotaline, as peak systolic right ventricular pressure increased to 66.35±1.03 mm Hg and right ventricular ejection fraction reduced to 41.99±1.27%. PH progressed to RHF by day 30 (right ventricular pressure, 72.41±1.87 mm Hg; RV ejection fraction, 29.25±0.88%), and mortality was ≈75% in RHF rats. Genistein therapy resulted in significant improvement in lung and heart function as right ventricular pressure was significantly reduced to 43.34±4.08 mm Hg and right ventricular ejection fraction was fully restored to 65.67±1.08% similar to control. Genistein reversed PH-induced pulmonary vascular remodeling in vivo and inhibited human pulmonary artery smooth muscle cell proliferation by ≈50% in vitro likely through estrogen receptor-β. Genistein also reversed right ventricular hypertrophy (right ventricular hypertrophy index, 0.35±0.029 versus 0.70±0.080 in RHF), inhibited neonatal rat ventricular myocyte hypertrophy, and restored PH-induced loss of capillaries in the right ventricle. These improvements in cardiopulmonary function and structure resulted in 100% survival by day 30. Genistein restored PH-induced downregulation of estrogen receptor-β expression in the right ventricle and lung. In conclusion, genistein therapy not only rescues preexisting severe PH but also prevents the progression of severe PH to RHF.     

The effects of concurrent training (aerobic-resistance) and milk consumption on some markers of bone mineral density in women with osteoporosis

Background

Osteoporosis is a skeletal metabolic disorder characterized by low bone mineral density (BMD) and reduced bone strength leading to higher bone fractures risk. The present study attempted to investigate the effects of concurrent training (aerobic-resistance) and milk consumption on some markers of BMD in women with osteoporosis.

Methods

For this purpose, forty women diagnosed with osteoporosis within an age range of 30-45?years were divided into four groups of ten including concurrent training-milk, concurrent training, milk consumption and control group. The concurrent exercises were performed in ten weeks with three sessions in each week including aerobic training (running at 55–75% of maximum heart rate) and resistance training (4 move in a circle performed two times with 10 repetition maximum (RM)). Milk consumption was two times of 250?ml per day in ten weeks. Before and after treatment, BMDs in the hip and lumbar spine area were estimated with Dual-energy X-ray absorptiometry (DEXA) device and 5?cc blood was taken from a vein in the arm to determine the blood levels of 25-hydroxyvitamin D (25OH-D) and alkaline phosphatase (ALP).

Results

Based on the results, blood levels 25OH-D and ALP significantly increased in concurrent training-milk, concurrent training and milk group with higher increase in concurrent training-milk group (P?<?0.05). Furthermore, the right and left hip BMD in concurrent training-milk and concurrent training groups increased significantly with higher increase in concurrent training-milk group (p?<?0.05). Also, lumbar spine BMD increased significantly in concurrent training-milk and concurrent training (p?<?0.05).

Conclusions

It seems that combination of concurrent training and milk consumption has more efficient impacts on the BMD of young women diagnosed with osteoporosis compared to the milk or concurrent training groups alone. This treatment can be used as an effective way to improve BMD in young women with diagnosed osteoporosis.

     

Selenium Deficiency After Bariatric Surgery,Incidence and Symptoms: a Systematic Review and Meta-Analysis

Obesity Surgery - This study review the prevalence of selenium deficiency after bariatric surgery, incidence, and symptoms.&nbsp;A systematic literature search and meta-analysis was performed...     

An endoplasmic reticulum trafficking signal prevents surface expression of a voltage- and Ca2+-activated K+ channel splice variant

Protein delivery to restricted plasma membrane domains is exquisitely regulated at different stages of the cell trafficking machinery. Traffic control involves the recognition of export/retention/retrieval signals in the endoplasmic reticulum (ER)/Golgi complex that will determine protein fate. A splice variant (SV), SV1, of the voltage- and Ca(2+)-activated K(+) channel alpha-subunit accumulates the channel in the ER, preventing its surface expression. We show that SV1 insert contains a nonbasic, hydrophobic retention/retrieval motif, CVLF, that does not interfere with proper folding and tetramerization of SV1. Localization of proteins in the ER by CVLF is independent of its position; originally, on the first internal loop, SV1 insert or CVLF perform equally well if placed at the middle or end of the alpha-subunit intracellular carboxyl terminus. Also, CVLF is able to restrict the traffic of an independently expressed transmembrane protein, beta 1-subunit. CVLF is present in proteins across species and in lower organisms. Thus, CVLF may have evolved to serve as a regulator of cellular traffic.