Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) μg/mg vs. (0.974±0.060) μg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) μg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.
Mice ; Male ; Animals ; Pulmonary Fibrosis/pathology* ; Cannabinoid Receptor Agonists/metabolism* ; Collagen Type I/pharmacology* ; Collagen Type III/pharmacology* ; Hydroxyproline/pharmacology* ; Sodium Chloride/metabolism* ; Mice, Inbred C57BL ; Lung/pathology* ; Cannabinoids/adverse effects* ; Bleomycin/metabolism* ; Collagen/metabolism* ; Inflammation/pathology* ; RNA, Messenger/metabolism*

Humans ; Consensus ; Hypertension/therapy* ; Sodium Chloride, Dietary/adverse effects* ; China

Fructose intake has increased dramatically over the past century and the upward trend has continued until recently. Increasing evidence suggests that the excessive intake of fructose induces salt-sensitive hypertension. While the underlying mechanism is complex, the kidney likely plays a major role. This review will highlight recent advances in the renal mechanisms of fructose-induced salt-sensitive hypertension, including (pro)renin receptor-dependent activation of intrarenal renin-angiotensin system, increased nephron Na transport activity via sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter, increased renal uric acid production, decreased renal nitric oxide production, and increased renal reactive oxygen species production, and suggest actions based on these mechanisms that have therapeutic implications.
Blood Pressure ; Fructose ; adverse effects ; Humans ; Hypertension ; chemically induced ; physiopathology ; Kidney ; physiopathology ; Nitric Oxide ; metabolism ; Reactive Oxygen Species ; metabolism ; Renin-Angiotensin System ; Sodium Chloride, Dietary ; adverse effects ; Sodium-Hydrogen Exchanger 3 ; metabolism ; Uric Acid ; metabolism

Bamboo salt (BS) is a traditional Korean food, and has been reported to have anti-cancer, anti-inflammatory, and anti-metastatic effects. However, the anti-atopic dermatitis (AD) activity of BS has not been described yet. In the present study, we examined the preventive effect of BS on AD. The effect of oral administration of BS was tested in a 2, 4-dinitrofluorobenzene (DNFB)-induced AD animal model, by histological analysis, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, caspase-1 assay, and Western blotting analysis. BS administration reduced the total clinical severity and scratching frequencies, compared with the AD group. In the serum of DNFB-induced AD mice, the levels of IgE, histamine, thymic stromal lymphopoietin (TSLP), interleukin (IL)-5, and IL-13 were significantly reduced by BS treatment. BS significantly reduced the protein and mRNA expression of TSLP, IL-6, and tumor necrosis factor-α in the AD skin lesions. BS markedly reduced the infiltration of inflammatory cells. Furthermore, the activation of caspase-1 was reduced by BS in the AD skin lesions. Our results suggested that BS should be considered as a candidate treatment for allergic inflammatory diseases including AD.
Animals ; Caspase 1 ; genetics ; immunology ; Dermatitis, Atopic ; chemically induced ; drug therapy ; genetics ; immunology ; Dinitrofluorobenzene ; adverse effects ; Disease Models, Animal ; Female ; Histamine ; immunology ; Humans ; Immunoglobulin E ; immunology ; Interleukin-13 ; genetics ; immunology ; Interleukin-5 ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Sodium Chloride, Dietary ; administration & dosage

PURPOSE: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. MATERIALS AND METHODS: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. RESULTS: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. CONCLUSION: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.
Animals ; Cholesterol, Dietary/administration & dosage ; *Disease Models, Animal ; Endothelium/surgery ; HMGB1 Protein/*adverse effects ; Iliac Artery/diagnostic imaging/pathology/surgery ; Injections, Intra-Arterial ; Macrophages ; Male ; Olive Oil/adverse effects ; Plaque, Atherosclerotic/*chemically induced/diagnostic imaging/pathology ; Rabbits ; Sodium Chloride/adverse effects ; Tomography, Optical Coherence ; Tumor Necrosis Factor-alpha/*adverse effects

This study was aimed to evaluate the agreement between the self-reported sodium intake level and 24-h urine sodium excretion level in Chinese. The 24-h urine collection was conducted among 2112 adults aged 18-69 years randomly selected in Shandong Province, China. The subjects were asked whether their sodium intake was low, moderate, or high. The weighted kappa statistics was calculated to assess the agreement between 24-h urine sodium excretion level and self-reported sodium intake level. One third of the subjects reported low sodium intake level. About 70% of the subjects had mean 24-h sodium excretion>9 g/d, but reported low or moderate sodium intake. The agreement between self-reported sodium intake level and 24-h urine sodium excretion level was low in both normotensive subjects and hypertensive subjects. These findings suggested that many subjects who reported low sodium intake had actual urine sodium excretion>9 g/d. Sodium intake is often underestimated in both hypertensive and normotensive participants in China.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Awareness ; China ; epidemiology ; Diet Records ; Diet Surveys ; Diet, Sodium-Restricted ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Hypertension ; epidemiology ; prevention & control ; Male ; Rural Population ; Sodium ; urine ; Sodium Chloride ; adverse effects ; Sodium, Dietary ; administration & dosage ; Surveys and Questionnaires ; Young Adult

OBJECTIVETo observe the effect of composite factors, like long-term high-salt & fat diet and alcohol abuse on blood viscosity and blood pressure in rats, and compare with a model induced by high molecular dextran, in order to build a chronic hyperviscosity aminal model which is similar to human hyperviscosity in clinic and lay a foundation for efficacy evaluation on traditional Chinese medicines.

METHODMale SD rats were randomly divided into the normal group, the high molecular dextran (HMD) group and the high salt & fat and alcohol (HSFA) group. The HMD group was given normal diet and water for 23 day and then 10% HMD through tail vein for 5 days. The HSFA group was fed with high salt and high fat diets every day and alcohol for 20 h x d(-1) for 13 weeks. After the modeling, whole blood viscosity and plasma viscosity were measured in the 5th, 8th and 11th week. Blood pressure was measured in the 5d, 7h, and 10th week. Red cell count (RBC) and hematocrit (HCT) were measured in the 11th week. PAgT, Fb, ET-1, NO, PGI, TXA2 contents of the normal group and the HSFA group were measured in the 13th week, and IECa21 content was measured with flow cytometry. Result: After the modeling, the HMD group was in good conditions with glossy hairs and active behaviors. The HSFA group was depressed with withered hairs and less activities. During the 5th-11th weeks, the HMD group and the HSFA group showed higher values in high and low shear whole blood viscosity (WBV) than the normal control group. The plasma viscosity (PV) of HMD rats was significantly increased only in the 5th week, and that of HSFA rats significantly increased in the 8"' and 11th week, particularly in the 11'h week. In the 111h week, the HSFA group showed significant increases in RBC and HCT. After the modeling, the blood pressure of HMD rats showed no significant changes, but the blood pressure of HSFA rats significantly increased during 7' and 101h weeks, particularly in the 10"' week. In the 13th week, PAgT, IECa2+, Fb, ET-1 of HSFA rats significantly increased, but with decreases in NO and PGI2.

CONCLUSIONLong-term high salt & fat and alcohol diets can cause abnormal blood viscosity in rats. WBV significantly increased since the 5th week in rats, and PV increased since the 8th week. The mechanism for increasing BV may be: (1) increases in RBC, HCT, and IECa2+, (2) PAgT increase, (3) Fb content increase, or (4) TXA2/PGI2, ET-1/NO imbalance. Although the modeling time with the method is longer than that with the HMD method, the model is more stable and moderate, and could lead to abnormal increases in WBV and PV; Whereas the HMD method only induced transient increase in plasma viscosity and abnormal increase in SBP. The model is more similar to traditional Chinese medicine syndromes and pathogenesis, with higher value for studies on efficacy of traditional Chinese medicines.

Alcoholism ; blood ; metabolism ; Animals ; Blood Pressure ; Blood Viscosity ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Ethanol ; adverse effects ; metabolism ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride, Dietary ; adverse effects ; metabolism

OBJECTIVE: To observe the effect of nasal endoscope negative pressure cleaning and sinupret drops to treat radiation nasosinusitis (RNS). METHOD: One hundred and fifty-three patients with nasopharyngeal carcinoma were randomly divided into treatment group A, B, C . Group A using nasal endoscope negative pressure cleaning and sinupret drops, group B using nasal endoscope negative pressure cleaning and normal saline spray washing, group C using saline nasal irrigation through nasal catheter. All patients with sinusitis condition were evaluated at the end of radiotherapy, three months and six months after radiotherapy. RESULT: Comparison between groups, three periods of RNS incidence, moderate to severe RNS incidence are A < B < C. Six months after radiotherapy, group A compared with group C, there are significant difference (P < 0.01), group A and group C compared with group B respectively, the difference was statistically significant (P < 0.05). CONCLUSION Nasal endoscope negative pressure cleaning and sinupret drops can significantly reduce the long-term incidence of RNS, especially obviously reduce the incidence of moderate to severe RNS,which is a practical and effective method to treat RNS.
Carcinoma ; Endoscopy ; Humans ; Incidence ; Nasal Cavity ; Nasal Lavage ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; radiotherapy ; Plant Extracts ; administration & dosage ; therapeutic use ; Radiotherapy ; adverse effects ; Sinusitis ; therapy ; Sodium Chloride

OBJECTIVETo determine the effects of transient receptor potential vanilloid type 1 (TRPV1) channel ablation and a chemokine receptor 2 (CCR2) antagonist on salt-sensitive hypertension-induced renal injury.

METHODSWild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks with or without a CCR2 antagonist, RS504393 (n=8 for all the 4 groups). Sham WT and TRPV1(-/-) mice (both n=7) underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin, 8-isoprostane and creatinine clearance for 24 hours were assayed during the experimental period and at the end of the 4-week treatment. The morphological analysis was performed in renal histological sections, including glomerulosclerosis, tubulointerstitial injury, and monocyte/macrophage infiltration.

RESULTSCompared to the corresponding control mice, DOCA-salt treatment in both WT and TRPV1(-/-) mice led to increased systolic blood pressure (SBP), enhanced urinary excretion of albumin and 8-isoprostane, decreased creatinine clearance, increased glomerulosclerosis and tubulointerstitial injury associated with enhanced monocyte/macrophage infiltration (all P<0.05), all of which were much more severe in TRPV1(-/-) mice compared to WT mice with the exception of blood pressure (all P<0.05). RS5043943 attenuated DOCA-salt-induced changes in renal function and morphology in WT and TRPV1(-/-) mice (all P<0.05). There was no difference in blood pressure among DOCA-salt WT and TRPV1(-/-) mice with or without RS505393 with the exception of sham WT and TRPV1(-/-) mice (all P>0.05).

CONCLUSIONSCCR2 antagonist inhibits DOCA-salt-induced renal injury and monocyte/macrophage infiltration in WT and TRPV1(-/-) mice with the greater in the latter strain. Activation of TRPV1 attenuates salt-sensitive hypertension-induced renal injury possibly via inhibition of CCR2-induced monocyte/macrophage infiltration.

Animals ; Hypertension ; complications ; pathology ; Kidney Diseases ; etiology ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, CCR2 ; antagonists & inhibitors ; physiology ; Sodium Chloride ; adverse effects ; TRPV Cation Channels ; physiology

OBJECTIVETo observe the level of blood sodium in patients hospitalized for heart failure with water-sodium retention treated with loop diuretics and risk factors of low blood sodium.

METHODSWe selected 1 378 acute decompensated heart failure patients who visited Anzhen Hospital, and they are treated with loop diuretics, 259 patients with weight loses more than 1 kg in one week was enrolled in the final analysis, and divided into 3 groups: Group A (weight reduction between 1-3 kg), Group B (weight reduction between 3-5 kg) and Group C (weight reduction over 5 kg). Blood sodium, creatinine and uric acid were compared among groups and risk factors of low blood sodium were analyzed.

RESULTSBlood sodium was similar before and post loop diuretics treatment in Group A, and reduced in group B ((138.28 ± 3.73) mmol/L vs. (139.34 ± 3.66) mmol/L, P < 0.05) and in Group C((137.60 ± 4.07) mmol/L vs. (139.44 ± 4.12) mmol/L, P < 0.05). Forty-six (17.8%) patients developed hyponatremia post loop diuretics treatment. Duration of loop diuretics use was the independent risk infector for hyponatremia (OR = 1.191, 95%CI 1.010-1.385).

CONCLUSIONSLoop diuretics use is safe for treating hospitalized patients for heart failure with water-sodium retention and the risk of developing hyponatremia is low. Duration of loop diuretics use is the independent risk factor of hyponatremia.

Acute Disease ; Creatinine ; Heart Failure ; complications ; drug therapy ; Humans ; Hyponatremia ; Risk Factors ; Sodium ; blood ; Sodium Potassium Chloride Symporter Inhibitors ; adverse effects ; therapeutic use ; Sodium, Dietary