OBJECTIVETo investigate the impact of antihypertensive medication timing on degree and stability of blood pressure (BP) lowering in patients with moderate and severe essential hypertension.

METHODSNinety patients were randomly assigned to take Valsartan and Felodiping together in the morning (group A), Valsartan in the morning and Felodiping in the evening (group B) or Felodiping in the morning and Valsartan in the evening (group C, n = 30 each). The morning dosage was titrated if the goal blood pressure was not achieved. Ambulatory blood pressure monitoring (ABPM) was performed on the first and 14(th) day of medication.

RESULTSThe BP reductions during nighttime and twenty-four in group B and C hours were similar (P > 0.05) but were significant more than those in group A (P < 0.05). The smoothness indexes of mean systolic, mean arterial blood pressure during nighttime and twenty-four in group B and C were similar but significantly higher than that in group A (P < 0.05). The smoothness index of diastolic pressure at nighttime in group B and C was similar but significantly higher than that in group A (P < 0.05).

CONCLUSIONMore significant and stable antihypertensive effects could be achieved by taking the two antihypertensive medications separately in the morning and at evening compared that taken the two drugs together in the morning.

Antihypertensive Agents ; administration & dosage ; Blood Pressure ; drug effects ; Drug Administration Schedule ; Drug Therapy, Combination ; Felodipine ; administration & dosage ; Humans ; Hypertension ; drug therapy ; Tetrazoles ; administration & dosage ; Valine ; administration & dosage ; analogs & derivatives ; Valsartan

OBJECTIVETo evaluate the efficacy and safety of a once daily valsartan/amlodipine 80/5 mg combination tablet in Chinese mild to moderate hypertensive patients without adequate blood pressure control by monotherapy.

METHODSTwo multicenter, randomized, double-blind, double dummy, active-controlled, parallel group trials were conducted. After a washout period (no medication) of 1-4 weeks, patients with Mean Sitting Diastolic Blood Pressure (MSDBP) > or = 95 mm Hg (1 mm Hg = 0.133 kPa) and < 110 mm Hg received a monotherapy of either Amlodipine 5 mg (in study 1) or valsartan 80 mg (in study 2) for 4 weeks. Patients with MSDBP > or = 90 mm Hg and < 110 mm Hg at the end of the monotherapy period were randomized to receive valsartan/amlodipine 80/5 mg treatment, or continue with the monotherapy.

RESULTSIn study 1, compared with amlodipine 5 mg, valsartan/amlodipine 80/5 mg once daily further reduced mean sitting systolic blood pressure (MSSBP)/MSDBP 4.4/3 mm Hg (P < 0.0001). In study 2, compared with valsartan 80 mg, valsartan/amlodipine 80/5 mg once daily further reduced MSSBP/MSDBP 6.4/4.2 mm Hg (P < 0.0001). The blood pressure (BP) control rates (BP < 140/90 mm Hg) of combination treatment group were 71.0% and 71.2% respectively, and significantly higher than the monotherapy groups in both trials. Incidence of adverse events was comparable in monotherapy and combination therapy groups.

CONCLUSIONOur results showed that valsartan/amlodipine 80/5 mg was superior to amlodipine 5 mg or valsartan 80 mg alone in lowering blood pressure and BP control in patients with mild to moderate hypertension not adequately controlled with amlodipine 5 mg or valsartan 80 mg monotherapy. No new or unexpected safety issues were identified with valsartan/amlodipine combination therapy compared with monotherapy.

Adult ; Amlodipine ; administration & dosage ; Antihypertensive Agents ; administration & dosage ; Blood Pressure ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged ; Tetrazoles ; administration & dosage ; Valine ; administration & dosage ; analogs & derivatives ; Valsartan

OBJECTIVETo evaluate the clinical efficacy of intradermal injection of methylene blue for treatment of moderate to severe acute thoracic herpes zoster and prevention of postherpetica neuralgia in elderly patients.

METHODSSixty-four elderly patients with herpes zoster were randomized to receive a 10-day course of intradermal injection of methylene blue and lidocaine plus oral valaciclovir (group A, 32 cases) and intradermal injection of lidocaine plus oral valaciclovir (group B).Herpes evaluation index, pain rating index, incidence of postherpetic neuralgia, and comprehensive therapeutic effect were compared between the two groups at 11, 30 and 60 days after the treatment.

RESULTSThe baseline characteristics were comparable between the two groups (all P>0.05). Compared with that in group B, the time for no new blister formation, blister incrustation and decrustation, and pain relief was significantly shortened in group A (P<0.05) with also obviously lower pain intensity after the treatment. The incidence of postherpetic neuralgia was significantly lower in group A than in group B at 30 days (P<0.05), but not at 60 and 90 days after the treatment. The total clinical response rate was 93.8% in group A, much higher than that in group B (62.5%, P<0.05).

CONCLUSIONIntradermal injection of methylene blue can effectively shorten the disease course, reduce the pain intensity and prevent the development of postherpetic neuralgia in elderly patients with herpes zoster.

Acyclovir ; administration & dosage ; analogs & derivatives ; therapeutic use ; Aged ; Herpes Zoster ; complications ; Humans ; Incidence ; Injections, Intradermal ; Lidocaine ; administration & dosage ; therapeutic use ; Methylene Blue ; administration & dosage ; therapeutic use ; Neuralgia, Postherpetic ; therapy ; Pain Measurement ; Valine ; administration & dosage ; analogs & derivatives ; therapeutic use

The investigation was aimed to determine prognostic factors related to postherpetic neuralgia (PHN), and treatment options for preventing PHN. The data showed 34 (17.0%) out of 188 patients with herpes zoster had severe pain after 4 weeks, and 22 (11.7%) after 8 weeks, compared with 109 (58.0%) at presentation. The age (>or=50 yr), surface area involved (>or=9%), and duration of severe pain (>or=4 weeks) might be the main factors that lead to PHN. On the other hand, gender, dermatomal distribution, accompanied systemic conditions, and interval between initial pain and initiation of treatment might not be implicated in PHN. The subjects were orally received antiviral (valacyclovir), tricyclic antidepressant (amitriptyline), and analgesic (ibuprofen) as the standard treatment in the group 1. In addition to the standard medication, lidocaine solution was sub- and/or perilesionally injected in the group 2, while lidocaine plus prilocaine cream was topically applied to the skin lesions in the group 3. The rates of PHN in the 3 treatment groups were not significantly different, suggesting adjuvant anesthetics may not be helpful to reduce the severity of pain.
Acyclovir/administration & dosage/*analogs & derivatives ; Adolescent ; Adult ; Aged ; Amitriptyline/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Antidepressive Agents, Tricyclic/administration & dosage ; Antiviral Agents/administration & dosage ; Child ; Drug Therapy, Combination ; Female ; Herpes Zoster/*complications/drug therapy/physiopathology ; Humans ; Ibuprofen/administration & dosage ; Male ; Middle Aged ; Neuralgia/drug therapy/*etiology/physiopathology/prevention & control ; Prognosis ; Time Factors ; Valine/administration & dosage/*analogs & derivatives

OBJECTIVE: To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. MATERIALS AND METHODS: This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (K(trans)) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. RESULTS: P792 group showed a more prominent decrease in K(trans) and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.
Animals ; Antineoplastic Agents/therapeutic use ; Benzophenones/therapeutic use ; Disease Models, Animal ; Heterocyclic Compounds/administration & dosage/*chemistry ; Liver Neoplasms/drug therapy/pathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Organometallic Compounds/administration & dosage/*chemistry ; Rabbits ; Reproducibility of Results ; Valine/analogs & derivatives/therapeutic use

Animals ; Chemokine CCL2 ; analysis ; genetics ; Diabetes Mellitus, Experimental ; drug therapy ; physiopathology ; Drug Therapy, Combination ; Fatty Acids, Monounsaturated ; administration & dosage ; Indoles ; administration & dosage ; Kidney ; drug effects ; physiopathology ; Male ; NF-kappa B ; analysis ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; administration & dosage ; Transcription Factor RelA ; Valine ; administration & dosage ; analogs & derivatives ; Valsartan

OBJECTIVETo observe the effect of combined therapy with Xuezhikang Capsule (XZK) and Valsartan on left ventricular hypertrophy (LVH) and heart rate turbulence (HRT) in hypertensive patients.

METHODSNinety primary hypertensive patients with LVH were randomly assigned to three groups. Basic treatment, including aspirin, beta-blockers, calcium antagonists, etc. were administered to all patients. Additionally, Valsartan (VS, 80 mg once a day) was given to the 30 patients in the VS group. Valsartan (in the same dosage) and XZK (600 mg, twice a day) were given to the 32 patients in the Chinese medicine (CM) group, while none was given to the 28 patients in the control group. The therapeutic course lasted for 24 months. Changes in left ventricular mass index (LVMI) measured by cardiac ultrasonic indices, HRT parameters, including the original heart rate (TO) and slope coeffificient (TS), systolic and diastolic blood pressures (SBP and DBP), as well as blood cholesterol level (TC) were measured before and after treatment.

RESULTSAfter treatment, TO and LVMI were lowered, while TS increased in both the VS group and the CM group (P<0.01), but changed insignificantly in the control group. Significant differences between the CM group and the control group were shown in terms of TO, LVMI, SBP, DBP and TS (P<0.01); and between the CM group and the VS group in terms of TO, LVMI and TS (P<0.01). Moreover, HRT parameters showed an evident correlation with LVMI (r=0.519-0.635, P<0.01).

CONCLUSIONCombined therapy with XZK and Valsartan can improve hypertensive LVH and HRT parameters, and lessen the damage on the autonomous nervous system.

Administration, Oral ; Aged ; Antihypertensive Agents ; administration & dosage ; adverse effects ; Arrhythmias, Cardiac ; drug therapy ; etiology ; Capsules ; Combined Modality Therapy ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Heart Rate ; drug effects ; Humans ; Hypertension ; complications ; drug therapy ; Hypertrophy, Left Ventricular ; drug therapy ; etiology ; Hypolipidemic Agents ; administration & dosage ; adverse effects ; Integrative Medicine ; methods ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Tetrazoles ; administration & dosage ; adverse effects ; Treatment Outcome ; Valine ; administration & dosage ; adverse effects ; analogs & derivatives ; Valsartan

BACKGROUNDPodocyte has inflammatory role in the development of diabetic nephropathy (DN). Mycophenolate mofetil (MMF), an anti-inflammatory agent, can suppress macrophage infiltration and reduce renal injury in streptozotocin-induced diabetic rats. Angiotensin II receptor blocker (ARB), another renal protecting agent, can decrease podocyte loss in DN. In this study, we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) and nephrin to evaluate podocyte's role in inflammatory reaction in DN, observe and compare the effect of MMF alone and in combination with valsartan, on preventing podocyte loss in streptozotocin (STZ) induced diabetic rats.

METHODSDiabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ (65 mg/kg). The successfully induced diabetic rats were randomly divided into four groups: diabetes without treatment group (DM), valsartan treated group (DMV), MMF treated group (DMM), and combined therapy group (DMVM). Normal rats of the same sibling were chosen as control (NC). At the end of the 8th week, serum biochemistry, 24-hour urinary protein (UP) and the ratio of kidney weight/body weight (RWK/B) were measured. The rats were sacrificed for the observation of renal histomorphology through light and electron microscope. Nephrin, desmin and MCP-1 levels were detected by semi-quantitative immunohistochemical assays. Real-time quantitative PCR was used to detect the mRNA levels of nephrin and MCP-1.

RESULTSCompared with group NC, serum glucose level, 24-hour UP and RWK/B in group DM were significantly higher (P < 0.01), and the nephrin mRNA level in DM group was significantly lower (P < 0.05). The nephrin mRNA expression levels in group DMV, DMM and DMVM were all higher than that of DM group (P < 0.05) and no significant differences were found among the three treatment groups (P > 0.05). Treatment with MMF, valsartan or their combination could significantly decrease the 24-hour UP and RWK/B, and suppress glomerulosclerosis and interstitial fibrotic lesions in diabetic rats. In diabetic rats, the high expressions of desmin and MCP-1 in kidney were suppressed by valsartan, MMF or their combination.

CONCLUSIONSPodocytes are involved in the inflammatory reaction of diabetic rats. MMF could suppress MCP-1 and desmin expression, enhance nephrin expression, and attenuate proteinuria in diabetic rats. The combined therapy of valsartan and MMF did not show any superiority over monotherapies on renal protection. MMF may have renoprotective effect in early stages of diabetic nephropathy through preventing podocytes loss and anti-inflammatory activity.

Animals ; Chemokine CCL2 ; analysis ; Desmin ; analysis ; Diabetic Nephropathies ; drug therapy ; pathology ; Drug Therapy, Combination ; Immunohistochemistry ; Male ; Membrane Proteins ; analysis ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Podocytes ; drug effects ; pathology ; Rats ; Rats, Wistar ; Tetrazoles ; administration & dosage ; therapeutic use ; Valine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Valsartan

Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; Animals ; Coronary Angiography ; Coronary Restenosis ; prevention & control ; Coronary Vessels ; pathology ; Drug Delivery Systems ; Immunohistochemistry ; Rabbits ; Receptor, Angiotensin, Type 1 ; analysis ; Receptor, Angiotensin, Type 2 ; analysis ; genetics ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Stents ; Tetrazoles ; administration & dosage ; Valine ; administration & dosage ; analogs & derivatives ; Valsartan

The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin II type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.
Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Animals ; Apoptosis ; drug effects ; Benzazepines ; administration & dosage ; Doxorubicin ; Drug Therapy, Combination ; Fas Ligand Protein ; Glomerulosclerosis, Focal Segmental ; chemically induced ; drug therapy ; pathology ; Kidney ; pathology ; Male ; Membrane Glycoproteins ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; administration & dosage ; Tumor Necrosis Factors ; biosynthesis ; genetics ; Valine ; administration & dosage ; analogs & derivatives ; Valsartan ; fas Receptor ; biosynthesis ; genetics