CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.
BACKGROUND/OBJECTIVES: Nutritional status and food intake during pregnancy and lactation can affect fetal programming. In the current metabolic syndrome epidemic, high-fructose diets have been strongly implicated. This study investigated the effect of maternal high-fructose intake during pregnancy and lactation on the development of metabolic syndrome in adult offspring. SUBJECTS/METHODS: Drinking water with or without 20% fructose was administered to female C57BL/6J mice over the course of their pregnancy and lactation periods. After weaning, pups ate regular chow. Accu-Chek Performa was used to measure glucose levels, and a tail-cuff method was used to examine systolic blood pressure. Animals were sacrificed at 7 months, their livers were excised, and sections were stained with Oil Red O and hematoxylin and eosin (H&E) staining. Kidneys were collected for gene expression analysis using quantitative real-time Polymerase chain reaction. RESULTS: Adult offspring exposed to maternal high-fructose intake during pregnancy and lactation presented with heavier body weights, fattier livers, and broader areas under the curve in glucose tolerance test values than control offspring. Serum levels of alanine aminotransferase, aspartate aminotransferase, glucose, triglycerides, and total cholesterol and systolic blood pressure in the maternal high-fructose group were higher than that in controls. However, there were no significant differences in mRNA expressions of renin-angiotensin-aldosterone system genes and sodium transporter genes. CONCLUSIONS: These results suggest that maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome with hyperglycemia, hypertension, and dyslipidemia in adult offspring.
This study investigated the effect of endurance exercises on blood pressure, angiogenesis, and the vascular endothelial growth factor (VEGF) expression in the skeletal muscle of spontaneously hypertensive rats (SHR). Five week old SHRs and Wistar-Kyoto rats (WKY) were randomly divided into 3 groups: Wistar-Kyoto rats (WKY, n=9), SHR control (SHR-C, n=9), and SHR endurance exercise training (SHR-E, n=9). Endurance exercise training was performed on a treadmill (12-20 m/min, 0% grade, 60 min/day, 5 days/week, 16 weeks). Systolic blood pressure was monitored with the tail-cuff method. The expression of VEGF protein and capillary density were identified using western blotting and H&E staining in the soleus muscle, respectively. Systolic blood pressure was reduced by endurance exercise in SHR ($p$ <0.05). The capillary density of skeletal muscles in SHR-C was lower than in WKY ($p$ <0.05), but it was recovered by endurance exercise training (SHR-E) compared to SHR-C ($p$ <0.05), and VEGF protein was also increased by endurance exercise training compared to SHR-C ($p$ <0.05). These data suggest that the enhancement of capillary density via an increase of VEGF expression in skeletal muscles by endurance exercise training could be an important factor to inhibit blood pressure elevation in SHR.
This study was performed to determine the effect of low-intensity resistance training with blood flow restriction (BFR) on muscle volume and strength in elderly women. Sixteen elderly women (70.9±4.6 years) were divided into low (30% 1RM) and high (75% 1RM) intense resistance training groups. Tourniquet cuff (Zimmer, Germany) for BFR was applied only to the right leg during the training period. All subjects performed unilateral leg press, leg extension and leg curl (3 sets×12 repetitions) for 10 weeks (2d/wk). Blood pressure was increased from 110 to 240 mmHg during the training period at the most proximal region of exercised leg. Muscle volume and cross-sectional area (CSA) were measured by MRI and body composition was monitored by dual-energy X-ray absorptiometry (DEXA) and isokinetic muscular strength were analyzed in both legs. The quadriceps CSA (15.2%, p<.001) and muscle volume (13.8%, p<.001) were increased in high-intense trained leg with BFR and the increased rate was highest among groups. The quadriceps CSA (9.8%, p<.001) and muscle volume (6.9%, p<.001) were increased in low-intensity training group with BFR and their increased rates were higher than control groups. The strength by exercise training was significantly improved in all groups and tended to be higher in BFR groups. These results demonstrate low-intensity resistance training with blood flow restriction could be an effective way to improve muscle volume and strength in elderly women.
Purpose: This study examined the effects of a program designed to prevent ventilator-associated pneumonia (VAP) on VAP rate and endotracheal colonization. The program focused on aspiration prevention and oral care. Methods: A nonequivalent control group post-test only design was utilized. One hundred patients admitted to a medical intensive care unit (MICU) or coronary care unit (CCU) were assigned to either a experimental group (n=50) or a control group (n=50). The participants were selected 48 hours following an endotracheal intubation. VAP prevention program given to the experimental group includes keeping the head of the bed to $30^{\circ}{\sim}45^{\circ}$ high, maintaining continuous endotracheal cuff pressure at 25 cm $H_2O$, performing endotracheal suction before change position, and providing oral care with 0.1% chlorhexidine every four hours. The control group received usual care. Data were analyzed using t-test, $x^2$ test, Mantel-Haenszel $x^2$ and Cox proportional harzard regression model. Results: The experimental group showed a lower VAP rate than the control group although the difference was not statistically significant ($x^2=0.79$, p=.375). The experimental group showed lower colonization in tracheal secretion than the control group ($x^2=14.59$, p<.001). Conclusion: Results showed that a VAP prevention program is effective in reducing colonization of tracheal secretion. Therefore, VAP prevention programs are recommended as an ICU nursing intervention.
Journal of the Korean Society of Physical Medicine
/
v.10
no.1
/
pp.63-69
/
2015
PURPOSE: Low-intensity exercise with transient restriction of blood flow to muscle could be an alternative rehabilitation method which avoids the problems associated with conventional high-intensity exercise. However, the mechanism of low-intensity exercise with transient restriction of blood flow is not clearly known. Thus, the purpose of this study was to investigate the mechanism of improvement of muscular function after low-intensity exercise with transient restriction of blood flow using H-reflex analysis. METHODS: Twenty one healthy young adults with no medical history of neurological or musculoskeletal disorder voluntarily participated in this study. The ${\alpha}$-motor neuron excitability of the triceps surae was assessed using the H-reflex. The amplitude of the M-wave and H-reflex were measured across three conditions: rest, after low-intensity exercise without restriction of blood flow and after low-intensity exercise with restriction of blood flow. The subjects performed low-intensity ankle plantar flexion exercise at their own pace for one minute without or with transient restriction of blood flow achieved by a sphygmomanometer cuff on popliteal fossa at a pressure of 120mm of mercury(120 mmHg). RESULTS: No significant changes of the excitability of the ${\alpha}$-motor neuron were obtained across three different conditions. CONCLUSION: This study found that low-intensity exercise with transient restriction of blood flow did not influence to ${\alpha}$-motor neuron excitability of the triceps surae. From the results, I could come to the conclusion that further study will be required.
Hong Sung-Jin;Kim Kyo-Sun;Kim Pyung-Kil;Park Kyung-Hwa;Kim Kee-Hyuck
Childhood Kidney Diseases
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v.6
no.2
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pp.169-177
/
2002
Purpose: Hypertension accelerates the progression of chronic renal disease, whether it results from, or causes, the renal disease. Therefore, the control of hypertension is one of the important factors that retard the rate of renal deterioration. We compared the effects of different antihypertensive agents on renal function and glomerular morphology In subtotal nephrectomized rats. Materials and methods: After induction of chronic renal failure with 5/6 nephrectomy, the rats were divided into three groups; control group (Group C), enalapril group (Group E), and nicardipine group (Group N). Systolic blood pressure was measured by tail cuff method every 4 weeks until 12 weeks after nephrectomy. At 12 weeks after nephrectomy, all rats were placed in metabolic cages for 24 hour urine collections to measure urinary protein and creatinine excretion. After urine collection and blood sampling for serum creatinine, all rats were sacrificed. The renal tissue was processed for morphometric study with light microscope and electron microscope. Results: 1. The blood pressure of Group C increased progressively, but both enalapril and nicardipine prevented the development of hypertension, and the two drugs were equally effective in maintaining normal blood pressure throughout the study. 2. Twenty-four hour urinary protein excretion was lower in Group E compared to Group C and Group N 3. Mesangial expansion score in both treated groups were significantly lower than the control group. Mean glomerular volume in Group E was significantly reduced compared to Group C and Group N. There was no significant difference in mean glomerular volume between Group C and Group N. 4. There was no significant difference in podocyte structural changes, estimated by filtration slit length density, among control, enalapril and nicardipine treated groups. Conclusion: Control of hypertension with enalapril or nicardipine afforded considerable protection from mesangial expansion in the rat remnant kidney model. But protein excretion and glomerular growth were significantly reduced in Group E compared to Group N. There was no significant difference in podocyte structural changes among the 3 groups.
Aims: Acupuncture has been used for the treatment of essential hypertension, but the efficacy and the mechanism of acupuncture in prevention of hypertension are still unclear. We tested the hypothesis that electroacupuncture (EA) applied to Baekhoe (GV20) changes NO/NOS system during development of hypertension in spontaneously hypertensive rats (SHR), and thereby causes the delay of development of hypertension in SHR. Methods: The male SHR rats in the developmental stages of hypertension (7-8 weeks) were randomly divided into three groups (control group, GV20 acupuncture group, and tail acupuncture group). And the age matched Wistar Koyto Rats (WKY) were randomly divided into two groups (nagative control, GV20 acupuncture group). EA treatments (10Hz, 1mA, 0.1ms) were carried out for 25 min/day for five consecutive days. The systolic blood pressure (SBP) was determined in conscious rats by the tail-cuff method using automatic BP mornitoring system. We investigated the activations of inducible NO synthase (iNOS) in nuclei of solitary tract (NTS) and rostral ventrolateral medulla (RVLM) of SHR by the western blotting method. Results: The SBP after the termination of EA stimulation applied to the GV20 was stabilized at $169.14{\pm}3.67$ mmHg which is lower value than that of the control group. The SBP of control group was elevated to $178.14{\pm}3.49$ mmHg. In addition, we evaluated NOS activity as well as iNOS protein expression of NTS and RVLM in both of SHR and WKY. The iNOS activity in NTS was significantly higher in SHR than in WKY. Furthermore, the iNOS activity of NTS showed significant decreases in EA groups compare to that of non treated SHR group. Although iNOS expression of RVLM showed non significant changes between SHR and WKY, EA significantly enhanced the iNOS expression in SHR. Our data support the hypothesis that delayed development of hypertension and altered iNOS expression of NTS and RVLM by EA stimulations in SHR rats. Conclusions: The findings demonstrate that acupuncture can change NO/NOS system in NTS and RVLM, and exert beneficial role on development of hypertension.
The aim of this study was to determine if a low-molecular weight casein hydrolysate has an anti- hypertensive effect in spontaneously hypertensive rats (SHR). Prior to the in vivo experiment, the casein hydrolysate was confirmed to be resistant to gastrointestinal digestion by confirming the retention of its potency as an inhibitor of angiotensin I-concerting enzyme after incubation with pepsin, trypsin, or chymotrypsin. The in vivo anti-hypertensive effect of the hydrolysate was determined by the tail cuff method. Following an oral administration of the hydrolysate solution, the systolic blood pressure (SBP) decreased by 12.9% (-28.9mmHg; P<0.05) at 3 h after the administration at a dose of 500mg/kg body weight. When the hydrolysate was administered as an emulsion with 30% egg yolk, its anti-hypertensive effect was even more greater at the same dose(-30.8mmHg or -15.9%; P<0.01). In a 50-day long-term trial where the casein hydrolysate was administered once a day, the SBP-lowering effect of the hydrolysate was apparent (P<0.05) from day 35 through the end. Moreover, organ weights and plasma glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities of the administered SHR were not significantly different from those of controls at the end of the long-term trial.
Objective: The objective of this research is to quantitatively analyze muscle activities of arm and shoulder, according to direction in various types of one-handed manual material handling, based on surface electromyography. Background: Workers in industrial sites frequently carry out one-handed manual material handling using arm and shoulder muscles. Therefore, chronic load and accumulated fatigue occur to arm and shoulder muscles, which becomes a main cause of upper arm and shoulder musculoskeletal disorders. The shoulder muscles have widely range of motion, and complex interactions take place among various muscles including rotator cuff muscles. In this regard, research on interactions among should muscles, according to such various dynamic motions, is required. Method: Ten male subjects in their 20s participated in this research. This research considered upward, downward, leftward, rightward, forward and backward directions and fourteen muscles around arm and shoulder (biceps brachii and trapezius, etc.) as independent variables. The mean muscle activity was set as the dependent variable. This research extracted $4^{th}{\sim}7^{th}$ repetition signals according to ten times of repetitive muscle contraction, and analyzed the muscle activity concerned using the envelope detection technique. Results: The mean muscle activity of upward direction was analyzed highly statistically significant. The reason is that the effect of gravity works to arm and shoulder muscles. Also, it is conjectured that deformation of coracoacromial ligament was caused, and its contact pressure increased, due mainly to the shoulder flexion, and therefore load was analyzed high. Muscle activity was analyzed significantly low, according to concentric ballistic motion used in the concentric contraction phase by storing elastic energy in the eccentric contraction phase with a motion to bring the weight to the front of subject's body as to downward, leftward and backward directions. Because, elbow joint's flexion-extension motions mainly occurred, biceps brachii was analyzed high muscle activity as the prime mover. Conclusion: The information on the quantitative load of muscles can be applied to ergonomic work design for one-handed manual material handling to minimize muscle load. Application: This research has effectively identified muscle activity according to dynamic contraction by applying an envelope detection technique. The results can be used for ergonomic work design to minimize muscle load during the one-handed manual material handling, according to each direction. The research results are expected to be used for musculoskeletal disorder prevention and physiotherapy in the rehabilitation medical field, based on the muscle load of arm and shoulder in various directions.
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