Alkaline Phosphatase ; metabolism ; Asian Continental Ancestry Group ; Bone Density Conservation Agents ; therapeutic use ; China ; Denosumab ; therapeutic use ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Hyperlipidemias ; complications ; Hypertension ; complications ; Middle Aged ; Osteitis Deformans ; complications ; diagnostic imaging ; drug therapy ; metabolism ; Pelvic Bones ; diagnostic imaging ; Renal Insufficiency, Chronic ; complications ; Singapore ; Tibia ; diagnostic imaging ; Treatment Outcome

BACKGROUNDAtherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance.

METHODSA total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed.

RESULTSFibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026.

CONCLUSIONSFbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; Aged ; Antihypertensive Agents ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Essential Hypertension ; blood ; complications ; drug therapy ; physiopathology ; Female ; Humans ; Kidney Diseases ; blood ; etiology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; etiology ; physiopathology ; Risk Factors ; Serum Amyloid A Protein ; metabolism ; Stroke ; blood ; etiology ; physiopathology ; Tryptases ; blood

As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged.
Arrhythmias, Cardiac ; Atherosclerosis ; Brain ; Cerebrovascular Disorders ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dyslipidemias ; Fatty Liver ; Heart ; Humans ; Hypertension ; Inflammation ; Insulin Resistance ; Kidney Diseases ; Liver ; Mass Screening ; Metabolic Diseases ; Metabolism ; Non-alcoholic Fatty Liver Disease* ; Obesity ; Oxidative Stress ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Risk Assessment ; Stroke

Sunitinib is a multi-target tyrosine kinase inhibitor used to treat gastrointestinal stromal tumors, renal cell carcinoma, and pancreatic neuroendocrine tumors. The most common adverse reactions are known to be nausea, fatigue, diarrhea, stomatitis, esophagitis, hypertension, skin toxicity (hand-foot syndrome), hypothyroidism, and reduction in the cardiac output of the left ventricle. Herein, we report the case of a 57 year-old female who visited our hospital complaining of epigastric pain. She had been taking sunitinib at 25 mg/day to treat a metastatic pancreatic neuroendocrine tumor. Upon computed tomography performed on admission, we observed that fluid had collected around the pancreas. Laboratory analysis revealed hypertriglyceridemia (triglycerides 993 mg/dL). Tyrosine kinase inhibitors are known to have limited effects on lipid metabolism. In this case, we suggest that hyperglycemia seems to have had a limited effect on lipid levels. We are rather of the view that hyperglycemia, a history of distal pancreatectomy, and hypothyrodisim, indirectly caused the observed hypertriglyceridemia.
Carcinoma, Renal Cell ; Cardiac Output ; Diarrhea ; Esophagitis ; Fatigue ; Female ; Gastrointestinal Stromal Tumors ; Heart Ventricles ; Humans ; Hyperglycemia ; Hypertension ; Hypertriglyceridemia* ; Hypothyroidism ; Lipid Metabolism ; Nausea ; Neuroendocrine Tumors* ; Pancreas ; Pancreatectomy ; Protein-Tyrosine Kinases ; Skin ; Stomatitis

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA> or =6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.
Adult ; Allopurinol/therapeutic use ; Antimetabolites/therapeutic use ; Benzbromarone/therapeutic use ; Cardiovascular Diseases/epidemiology/prevention & control ; Comorbidity ; Diabetes Mellitus, Type 2/epidemiology/prevention & control ; Enzyme Inhibitors/therapeutic use ; Female ; Gout/*drug therapy/*prevention & control ; Gout Suppressants/*therapeutic use ; Humans ; Hypertension/epidemiology/prevention & control ; Male ; Middle Aged ; Renal Insufficiency, Chronic/epidemiology/prevention & control ; Retrospective Studies ; Thiazoles/therapeutic use ; Uric Acid/*blood/metabolism ; Uricosuric Agents/therapeutic use ; Urolithiasis/epidemiology/prevention & control

It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P<0.001 for each analysis). When we estimated uAGT/cr in the 24HUna/cr groups by ANCOVA, the uAGT/cr in patients with > or =200 mEq/g cr was higher than in patients with <100 mEq/g cr (708 [95% CI, 448-967] vs. 334 [95% CI, 184-483] pg/mg cr, P=0.014). Similarly, uMDA/cr was estimated as 0.17 (95% CI, 0.14-0.21) pM/mg cr in patients with <100 mEq/g cr and 0.27 (95% CI, 0.20-0.33) pM/mg cr in patients with > or =200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.
Adult ; Aged ; Angiotensinogen/urine ; Chemokine CCL2/urine ; Creatine/urine ; Demography ; Female ; Follow-Up Studies ; Humans ; Hypertension/complications ; Male ; Malondialdehyde/urine ; Middle Aged ; Reactive Oxygen Species/*metabolism ; Renal Insufficiency, Chronic/complications/*pathology ; Renin-Angiotensin System/*physiology ; Sodium, Dietary/*urine ; Urine Specimen Collection

OBJECTIVETo observe the effect of electric acupuncture (EA) on the Nogo receptors (NgR) protein expression in the cerebral cortex, the medulla oblongata, and the spinal cord of cerebral ischemia-reperfusion (I/R) stroke-prone renovascular hypertensive rats (RHRSP) with middle cerebral artery occlusion (MCAO) at different time points, and to investigate its possible mechanisms for remote-organ injury of acute cerebral infarction (ACI).

METHODSThe RHRSP model was duplicated in male SPF grade SD rats. Then the MCAO model was prepared by a thread stringing method. Rats were divided into the hypertension group,the sham-operation group, the MCAO group, the EA group, and the sham-acupoint group by random number table method, 60 in each group. Rats in the MCAO group only received MCAO reperfusion treatment. Those in the sham-operation group only received surgical trauma. Baihui (DU20) and Dazhui (DU14) were needled in the EA group, once daily for a total of 28 days.The needles were acupunctured at the skin one cun distant from Baihui (DU20) and Dazhui (DU14) and then the same EA treatment was performed in the sham-acupoint group. At day 1, 7, 14, 28 after treatment, six rats were executed from each group, and their right cortex and medulla oblongata, and the left spinal cord were isolated. The infarct volume was detected by Nissl's staining method. The NgR expression was detect by Western blot.

RESULTS(1) In the cortex area: compared with the hypertension group,the NgR expression increased in the MCAO group at day 1,7,14,and 28 after MCAO (P < 0.05). Compared with the MCAO group, the NgR expression of the EA group and the sham-acupoint group were equivalent at 1 day af ter MCAO (P > 0.05). At day 7, 14,and 28 after MCAO, the NgR expression decreased in the EA group (P < 0.05), it was quite similar to that in the sham-acupoint group (P > 0.05). (2) In the medulla oblongata area: compared with the hypertension group, the NgR expression was equivalent in the sham-operation group. the MCAO group,the EA group, and the sham-acupoint group at 1 day after MCAO (P > 0.05). At day 7.14, and 28 after MCAO, the NgR expression increased in the MCAO group (P < 0.05). Compared with the MCAO group,the NgR expression decreased in the EA group at day 7, 14, and 28 after MCAO (P < 0.05), whereas it was similar in the sham-acupoint group (P > 0.05). (3) In the spinal cord area: compared with the hypertension group, the NgR expression was equivalent in the sham-operation group, the MCAO group,the EA group, and the sham-acupoint group at day 1 and 7 after MCAO (P > 0.05). At day 14 and 28 after MCAO, the NgR expression increased in the MCAO group (P < 0.05). Compared with the MCAO group, the NgR expression decreased in the EA group at day 14 and 28 after MCAO (P < 0.05), whereas it was equivalent in the sham-acupoint group (P > 0.05).

CONCLUSIONSIncreased NgR expression in the cerebral cortex, the medulla oblongata, and the spinal cord of cerebral infarct rats was an important reason for involving remote-organ injury of ACI. The protective effect of EA on hypertensive I/R cerebral injury rats might be closely related to down-regulating central nervous system myelin growth inhibition mediated factors Nogo-A receptor NgR protein expression.

Animals ; Cerebral Infarction ; metabolism ; therapy ; Disease Models, Animal ; Electroacupuncture ; GPI-Linked Proteins ; metabolism ; Hypertension, Renal ; metabolism ; therapy ; Male ; Medulla Oblongata ; metabolism ; Myelin Proteins ; metabolism ; Nogo Receptor 1 ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; metabolism ; Spinal Cord ; metabolism

This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy (STNx) were established. Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB). Benazepril was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin II (AngII) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.
Animals ; Antihypertensive Agents ; administration & dosage ; Benzazepines ; administration & dosage ; CLOCK Proteins ; metabolism ; Circadian Rhythm ; Drug Chronotherapy ; Gene Expression Profiling ; Hypertension, Renal ; drug therapy ; physiopathology ; Kidney ; drug effects ; physiopathology ; surgery ; Male ; Nephrectomy ; Rats ; Rats, Wistar ; Renin-Angiotensin System ; drug effects ; Treatment Outcome

Coronary artery disease (CAD) is the leading cause of death in patients with chronic kidney disease (CKD).Although many studies have shown a higher prevalence of CAD among these patients, the association between the spectrum of renal dysfunction and severity of CAD remains unclear. In this study, we investigate the association between renal function and the severity of CAD. We retrospectively reviewed the medical records of 1,192 patients who underwent elective coronary angiography (CAG). The severity of CAD was evaluated by Gensini score according to the degree of luminal narrowing and location(s) of obstruction in the involved main coronary artery. In all patients, the estimated glomerular filtration rate (eGFR) was independently associated with Gensini score (beta=-0.27, P < 0.001) in addition to diabetes mellitus (beta=0.07, P = 0.02), hypertension (beta=0.12, P < 0.001), low density lipoprotein (LDL)-cholesterol (beta=0.08, P = 0.003), and hemoglobin (beta=-0.07, P = 0.03) after controlling for other confounding factors. The result of this study demonstrates that decreased renal function is associated not only with the prevalence, but also the severity, of CAD.
Cholesterol, LDL/blood ; Coronary Angiography ; Coronary Artery Disease/*complications ; Diabetes Mellitus ; Female ; Glomerular Filtration Rate ; Hemoglobins/metabolism ; Humans ; Hypertension/*complications ; Kidney ; Kidney Function Tests ; Male ; Middle Aged ; *Organ Dysfunction Scores ; Renal Insufficiency, Chronic/*complications ; Retrospective Studies ; *Severity of Illness Index

Actins ; metabolism ; Adult ; Antigens, CD34 ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Glomus Tumor ; metabolism ; pathology ; Hemangiopericytoma ; metabolism ; pathology ; Humans ; Hypertension ; etiology ; Juxtaglomerular Apparatus ; metabolism ; pathology ; surgery ; ultrastructure ; Kidney Neoplasms ; complications ; metabolism ; pathology ; surgery ; ultrastructure ; Nephrectomy ; Wilms Tumor ; metabolism ; pathology