Trimetazidine limits the effects of myocardial ischaemia during percutaneous coronary angioplasty

This open-label, randomised, controlled study is aimed at assessing the effect of pre-treatment with the metabolic agent trimetazidine on the degree of ischaemia during percutaneous transluminal coronary angioplasty (PTCA). Overall 44 patients with one-vessel coronary artery stenosis (> 70%) in the medial part of the left anterior descending artery were included. One group (n = 22) was pre-treated with oral trimetazidine. The other group (n = 22) was the control. All patients (n = 44) were administered aspirin and conventional treatment. All patients underwent PTCA; stents were implanted in 11 trimetazidine patients and in seven control patients. The mean ST-segment elevation during all balloon inflations was significantly lower in the trimetazidine group than in the control group (-1.66 +/- 1.50 mm vs. 3.29 +/- 1.59 mm, p = 0.001). Maximal ST-segment elevations and mean ST elevation values during sequential balloon inflations were also significantly lower with trimetazidine (p = 0.018). The mean amplitude of the T-wave alterations during all balloon inflations was significantly lower with trimetazidine (3.09 +/- 2.39 mm vs. 6.83 +/- 4.31 mm; p = 0.001). Similarly, the maximal amplitude of the T-wave alterations was 4.50 +/- 2.90 mm with trimetazidine vs. 9.25 +/- 4.97 mm in control patients (p = 0.0005). Angina and rhythm disturbances were more frequent in the control group. Time from balloon inflation to onset of angina was 50 +/- 26.2 s with trimetazidine vs. 32 +/- 15.0 s, for control group (p = 0.03). The time to pain relief after deflation was 19.3 +/- 11.4 s with trimetazidine vs. 28.2 +/- 16.8 s (p = 0.001). Trimetazidine administered a few days before PTCA appears to be a cardioprotective agent for the prevention of myocardial ischaemia.     

Efficacy of trimetazidine in patients with recurrent angina: a subgroup analysis of the Trimpol II study

SUMMARY

Objectives: The revascularization procedures become more and more popular to treat coronary artery disease, in many countries. Some patients are free of angina after revascularization, without any documented re-stenosis present with recurrent angina symptoms after a period of time. The aim of this work was to assess the efficacy of trimetazidine in the subpopulation of patients with a history of PTCA or CABG, who were included in the TRIMPOL II study.

Methodology: A subgroup of 94 patients was retrospectively analysed from the Trimpol II study, a multicentre, double-blind randomised placebo-controlled trial in 426 patients with stable effort angina. These patients have a history of revascularization for coronary artery disease, and they are still symptomatic after 6 months despite a treatment with metoprolol (50?mg twice daily). They were randomly allocated to receive either trimetazidine (20?mg 3 times daily) or placebo for 12 weeks, on top of the β-blocker. Exercise test parameters, clinical efficacy and safety were assessed. Results were analysed using the Student test, the Mann–Whitney test or the Shapiro–Wilk test.

Results: Compared to placebo, the 12-week treatment with trimetazidine significantly improved: time to 1?mm ST segment depression (385.1?s ± 144.6?s versus 465.0?s ± 143.8?s [p < 0.01]); exercise test duration (466.9?s ± 144.8?s versus 524.4?s ± 131.5?s [p = 0.048]), total workload (9.0?m.e. ± 2.4?m.e versus 10.1?m.e. ± 2.4?m.e [p = 0.035]) as well as time to onset of angina (433.6?s ± 164?s versus 508.1?s ± 132.4?s [p = 0.031]). Weekly number of angina attacks and nitrate consumption were significantly reduced in the trimetazidine group when compared to placebo. Three mild gastro-intestinal side-effects were reported in the trimetazidine group.

Conclusion: These results show that trimetazidine provides anti-anginal efficacy in post-revascularized patients with recurrent angina despite a monotherapy with metoprolol. The treatment was well accepted.     

Comparison of lenograstim and filgrastim on haematological effects after autologous peripheral blood stem cell transplantation with high-dose chemotherapy

SUMMARY

Objective: To compare the efficacy of lenograstim and filgrastim on haematological recovery following an autologous peripheral blood stem cell transplantation (PBSCT) with high-dose chemotherapy.

Methods: A retrospective case-controlled study.

Results: Absolute neutrophil count (ANC) recovery above 0.5?×?10⁹?l^?1 and white blood cell (WBC) recovery above 4?×?10⁹?l^?1 for 3 consecutive days was achieved earlier with filgrastim than with lenograstim ((13.2?±?8.0 vs 19.0?±?10.0 days, p?=?0.004), (16.9?±?9.7 vs 29.9?±?16.6 days, p?=?0.001), respectively). The platelet recovery above 20 x 10⁹/l was also achieved earlier with filgrastim than with lenograstim (19.5?±?11.6 vs

27.2?±?13.8 days, p?=?0.006). Furthermore, filgrastim-treated patients received fewer days of granulocyte colony simulating factor (G-CSF) administration (12.5?±?7.0 vs 18.6?±?8.5 days, p?=?0.001) and spent less time in hospital (23.7?±?10.9 vs 32.0?±?17.6 days, p?=?0.009). Duration of antibiotic administration was also significantly shorter in the filgrastim group (13.6?±?7.6 vs 29.1?±?19.8 days, p?=?0.001). Conclusion: In patients undergoing PBSCT following high-dose chemotherapy, filgrastim significantly reduced the duration of neutropenia, thrombocytopenia and days of G-CSF administration, and led to earlier hospital discharge compared with lenograstim.     

Tumour necrosis factor-alpha levels in aqueous humour and serum from patients with uveitis: the involvement of HLA-B27

SUMMARY

Objective: To study the local and systemic levels of the tumour necrosis factor-α in patients with active uveitis and to determine the implication of TNF-α in rheumatological uveitis and to observe if this relationship is more significant in the B27 positive patients.

Patients and methods: Patients were selected on the basis of a diagnosis of uveitis of any aetiology. Data from 23 patients were stratified into two categories according to the presence or absence of systemic rheumatic disease. The first group comprised nine patients with rheumatic disease; the second group contained 14 patients without rheumatic disease. The patients were also sub-classified into those who were HLA-B27 positive (14 patients) and those who were not. TNF-α levels in serum and aqueous humour from a group of 16 patients with uncomplicated cataracts were analysed as a control group.

Results: In the control group (n?=?16) the serum TNF-α concentration was 13.1?±?2.9pg/ml and the aqueous humour concentration of TNF-α was 0.56?±?1.53?pg/ml. In uveitis patients (n?=?23) the serum TNF-α concentration was 35.35?±?26.77?pg/ml and the aqueous humour concentration of TNF-α was 15.1?±?1.70?pg/ml (p?<?0.01). In HLA-B27 positive patients (n?=?9) the serum TNF-α concentration was 45.56?±?34.17?pg/ml and the aqueous humour concentration of TNF-α was 15.89?±?0.93?pg/ml. In HLA-B27 negative patients (n?=?14) the serum TNF-α concentration was 28.79?±?19.38?pg/ml and aqueous humour concentration of TNF-α was 14.57?±?1.91?pg/ml (p?<?0.01).

Conclusions: The concentration of TNF-α in aqueous humour in patients who are HLA-B27 positive is significantly greater than in those who are B27 negative. No significant differences in the concentrations of TNF-α in serum or aqueous humour in patients with or without rheumatic diseases were detected. TNF-α is a cytokine that may participate actively in the pathogenesis of clinical uveitis.     

Effects of pioglitazone on metabolic control and blood pressure: a randomised study in patients with type 2 diabetes mellitus

SUMMARY

Aim: This Swiss multicentre study examined the efficacy and safety of oral pioglitazone in patients with type 2 diabetes.

Methods: Patients were randomised to pioglitazone at once-daily doses of 30mg for 20 weeks (n?=?76), 30?mg for 12 weeks followed by 45?mg for 8 weeks (n?=?74), or 45?mg for 20 weeks (n?=?84); 94.9% of patients completed 12 weeks and 88.9% completed all 20 weeks. Almost all (96.6%) patients received pioglitazone in combination with other anti-diabetic treatments.

Results: Mean HbA1c at baseline was 8.8?±?1.2%, and changes to endpoint were ?1.1?±?1.1%, ?1.1?±?1.4% and ?0.9?±?1.6%, respectively for the three dose groups (p?<?0.001 for each group). Triglyceride concentrations decreased in each group and the overall mean change during the study was ?0.58?mmol/l (p?<?0.001 versus baseline). HDL-cholesterol increased, with an overall mean change of 0.10?mmol?l^?1 (p?<?0.001 versus baseline). Blood pressure decreased from baseline, particularly for hypertensive patients with mean changes: systolic -10mmHg, p?<?0.001, diastolic-8mmHg, p?<?0.001 versus baseline. Serum alanine aminotransferase and γ-glutamyl transferase concentrations were significantly (p?<?0.001 for each) reduced during the study.

Conclusions: The study demonstrates the efficacy of pioglitazone 30?mg?day^?1 and 45?mg?day^?1 in the treatment of type 2 diabetes, with an improved lipid profile and decreased blood pressure in addition to improved glycaemic control.     

Effects of a Fixed Mixture of 25% Insulin Lispro and 75% NPL on Plasma Glucose during and after Moderate Physical Exercise in Patients with Type 2 Diabetes

Summary

Objective: To compare the plasma glucose (PG) response with a fixed mixture of 25% insulin lispro and 75% NPL (Mix25), prior to a meal and 3?h before exercise, to human insulin 30/70 (30/70) in patients with type 2 diabetes.

Research design and methods: Thirty-seven patients were treated in a randomized, open-label, 8-week, two-period crossover study. Mix25 was injected 5?min before breakfast and dinner throughout the study, as was 30/70 on inpatient test days and on outpatient dose titration days. Following the 4-week outpatient phase, patients were hospitalized, and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30?min, separated by 30?min rest, starting 3?h after a 339 kcal breakfast.

Results: The 2-h postprandial PG was significantly lower with Mix25 ((mean?±?SEM) 10.5?±?0.4 mmol/lvs 11.6?±?0.4 mmol/l; p?=?0.016). Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 (-3.6?±?0.29 mmol/l vs -4.7?±?0.31 mmol/l; p?=?0.001). The maximum decrease in PG over 6?h, after exercise onset, was significantly less with Mix25 (-4.3?±?0.4 mmol/l vs -5.9?±?0.4 mmol/l; p?<?0.001). The frequency of hypoglycemia (blood glucose (BG) < 3 mmol/l or symptoms) during the inpatient test was not different between treatments. During the outpatient phase, the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 (0.7?±?0.2 episodes/30d vs 1.2?±?0.3 episodes/30 d; p?=?0.042).

Conclusions: Mix25 resulted in better postprandial PG control without an increase in exercise-induced hypoglycemia. The smaller decrease in PG during the postprandial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70, especially for patients in tight glycemic control.     

Effect of smoking on retina nerve fiber layer and ganglion cell-inner plexiform layer complex

Purpose: The aim of this study is to show the effects of smoking on retina layers, especially retina nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer complex (GCIPL).

Materials and methods: Participants smoking for more than 10 years at least 1 pack of cigarettes a day and a control group, both including participants between ages of 20 and 50 years with no other systemic or ocular diseases were studied. After normality tests, an independent sample t test was used to analyze the differences in age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), GCIPL and RNFL values between the groups.

Results: There were 44 participants in each group. There were 32 (62.5%) men and 12(37.5%) women in smokers and 36 (77.88%) men and 8 (22.22%) women in control group. Mean ages were 39.85?±?8.41 and 38.66?±?10.47 years, mean spherical equivalent (SE) values were ?0.15?±?0.4 and 0?±?0.29 dioptries in smokers and control groups, respectively. The IOP, AXL, GCIPL and RNFL values were 17.58?±?3.41?mmHg, 23.69?±?0.56?mm, 84.3?±?5.83?μm and 92.3?±?3.51?μm in the smokers group and 18.5?±?2.91?mmHg, 23.45?±?0.72?mm, 86.11?±?8.02?μm and 97.66?±?8.23?μm in the control group. The inferior, superior, nasal and temporal values of RNFL quadrants were 123.18?±?26.14, 117.05?±?5.51, 64.95?±?8.67 and 63.5?±?6.88?μm in the smokers group and 130.81?±?11.8, 123.55?±?11.03, 72.44?±?9.84 and 58.44?±?7.48?μm in the control group. There were no significant difference of age, sex, SE, IOP, AXL and GCIPL values between the smokers and control groups (p?>?0.05). The mean RNFL was significantly thinner in the smokers group compared to controls (p?=?0.03, independent t test). Inferior and superior quadrants of RNFL decreased in smokers group (p?=?0.01 and p?=?0.03, respectively) but temporal and nasal quadrants did not seem to be changed (p?=?0.96 and p?=?0.07, respectively).

Discussion: Smoking may affect RNFL thickness but not GCIPL.     

Effect of chronic smoking on lens nucleus as assessed by Pentacam HR lens densitometry in young adults

Objective: To evaluate the effects of chronic tobacco smoking on lens nucleus by Pentacam HR lens densitometry (LD) in young adults.

Design: Prospective cross-sectional case series.

Methods: Thirty subjects (23?M, 7 F) who were chronic cigarette smokers (≥10 cigarettes/day for at least 2 years) (group 1) and another 30 subjects (23?M, 7 F) who did not smoke (group 2), were included in this study. The patients were matched for age and sex between the groups. The exclusion criteria were any history of ocular surgery, any systemic disorders and any ocular diseases except for mild refractive disorders. Lens densitometry measurements were done with the Pentacam HR (Oculus, Wetzlar, Germany). The Schirmer test and pachymetry measurements were also performed.

Results: Mean age of the patients for both groups was 28.90?±?8.20 years (range: 18–40 years). Mean lens densitometry (LD) measurements of Group 1 (chronic cigarette smoking group) were higher than those of Group 2 (control group) in all LD techniques; however only mean “peak” LD measurements showed a statistically significant difference between these two groups (Group 1: 8.67?±?0.61, Group 2: 8.44?±?0.70, p?=?0.04). The mean Schirmer test value was 12.43?±?5.60?mm in Group 1 and 13.00?±?4.26?mm in Group 2 (p?=?0.55). The mean central corneal thickness (CCT) value was 564.23?±?34.61?µm in Group 1 and 550.47?±?32.94?µm in Group 2 (p?=?0.03).

Discussion: The Pentacam HR LD seems to be an important option for the evaluation of lens nucleus in young adults, because it gives objective and quantitative data.

Conclusion: Although chronic smoking increases lens nucleus density in young adults, the effect is not statistically significant when compared with the control group.     

Effect of topiramate on choroidal thickness and anterior chamber parameters in the treatment of patients with migraine

Objective: To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine.

Methods: A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation.

Results: Mean age of the patients was 40.2?±?6.5?years. Mean CT at central fovea was 324?±?47?μm initially, 341?±?45?μm in the first month and 344?±?46?μm in the second month, thus first and second month measures were significantly higher than base values (p?p?=?0.001). Baseline ACD (3.66?±?0.22?mm) measures significantly decreased at the first month (3.63?±?0.22?mm) and second month (3.62?±?0.22?mm, p?=?0.009). Also, a significant reduction was detected in the first (36.2?±?4.9°) and second month (35.9?±?5.1°) ACA measures comparing with baseline (39.1?±?5.1°, p?=?0.05). A significant myopic shift was determined in the first and second month SphEq values (?0.08?±?0.6, ?0.10?±?0.6, respectively, p?=?0.05).

Conclusions: The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.     

Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers

Context: The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system.

Objective: This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats.

Material and methods: Animals were randomized into control, kernel extract (100 and 200?mg/kg/d, orally), dexamethasone (0.03?mg/kg/d, subcutaneously), dexamethasone?+?kernel (100 and 200?mg/kg/d, separately), and dexamethasone?+?captopril (25?mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX).

Results: Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128?±?7 vs. 105?±?3?mmHg, p?p?p?p?Conclusion: Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production.     

24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain

ABSTRACT

Background: Collagen hydrolysate is a nutritional supplement that has been shown to exert an anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis.

Objective: To investigate the effect of collagen hydrolysate on activity-related joint pain in athletes who are physically active and have no evidence of joint disease.

Design and setting: A prospective, randomized, placebo-controlled, double-blind study was conducted at Penn State University in University Park, Pennsylvania. Parameters including joint pain, mobility, and inflammation were evaluated with the use of a visual analogue scale during a 24-week study phase.

Study participants: Between September 2005 and June 2006, 147 subjects who competed on a varsity team or a club sport were recruited. Data from 97 of 147 subjects could be statistically evaluated.

Intervention: One hundred and forty-seven subjects (72 male, 75 female) were randomly assigned to two groups: a group (n?=?73) receiving 25?mL of a liquid formulation that contained 10?g of collagen hydrolysate (CH-Alpha)^* and a group (n?=?74) receiving a placebo, which consisted of 25?mL of liquid that contained xanthan.

Main outcome measures: The primary efficacy parameter was the change in the visual analogue scales from baseline during the study phase in relation to the parameters referring to pain, mobility, and inflammation.

Results: When data from all subjects (n?=?97) were evaluated, six parameters showed statistically significant changes with the dietary supplement collagen hydrolysate (CH) compared with placebo: joint pain at rest, assessed by the physician (CH vs. placebo (–1.37?±?1.78 vs. –0.90?±?1.74 (?p?=?0.025)) and five parameters assessed by study participants: joint pain when walking (–1.11?±?1.98 vs. –0.46?±?1.63, p?=?0.007), joint pain when standing (–0.97?±?1.92 vs. –0.43?±?1.74, p?=?0.011), joint pain at rest (–0.81?±?1.77 vs. –0.39?±?1.56, p?=?0.039), joint pain when carrying objects (–1.45?±?2.11 vs. –0.83?±?1.71, p?=?0.014) and joint pain when lifting (–1.79?±?2.11 vs. –1.26?±?2.09, p?=?0.018). When a subgroup analysis of subjects with knee arthralgia (n?=?63) was performed, the difference between the effect of collagen hydrolysate vs. placebo was more pronounced. The parameter joint pain at rest, assessed by the physician, had a statistical significance level of p?=?0.001 (–1.67?±?1.89 vs. –0.86?±?1.77), while the other five parameters based on the participants’ assessments were also statistically significant: joint pain when walking (?p?=?0.003 (– 1.38?±?2.12 vs. – 0.54?±?1.65)), joint pain when standing (?p?=?0.015 (–1.17?±?2.06 vs. –0.50?±?1.68)), joint pain at rest with (?p?=?0.021 (–1.01 ±1.92 vs. –0.47?±?1.63)), joint pain when running a straight line (?p?=?0.027 (–1.50?±?1.97 vs. –0.80?±?1.66)) and joint pain when changing direction (?p?=?0.026 (–1.87?±?2.18 vs. –1.20?±?2.10)).

Conclusion: This was the first clinical trial of 24-weeks duration to show improvement of joint pain in athletes who were treated with the dietary supplement collagen hydrolysate. The results of this study have implications for the use of collagen hydrolysate to support joint health and possibly reduce the risk of joint deterioration in a high-risk group. Despite the study's size and limitations, the results suggest that athletes consuming collagen hydrolysate can reduce parameters (such as pain) that have a negative impact on athletic performance. Future studies are needed to support these findings.     

Comparative Haemodynamic Responses to the First Dose of Short- and Long-acting ACE Inhibitors in Patients with Congestive Heart Failure

Summary

Background: Angiotensin Converting Enzyme inhibitors (ACEi's) confer significant mortality and morbidity benefits in all functional grades of chronic heart failure (CHF). However, physicians' concerns regarding the possible occurrence of first-dose hypotension appear to be a contributing factor to their under-utilisation in both hospital and primary care settings. We investigated whether long-acting and short-acting ACEi's differ in their haemodynamic responses to the first-dose in patients with CHF.

Method: This was a multicentre, randomised, open, two-parallel-group study of captopril 6.25?mg and perindopril 2mg. 240 patients with CHF, age 68.9?±?8.9 years, of whom 66% were male, NYHAII—IV, with average blood pressure baseline values of 132.2?±?16.2/78.5?±?10.5mmHg for systolic and diastolic blood pressure, and left ventricular ejection fraction (LVEF) of 31.3?±?7.4% received either captopril (n?=?124) or perindopril (n?=?116). Blood pressure was continuously monitored during the 8?h following drug intake. Minimum levels and maximum decreases in systolic, diastolic and mean arterial pressures were measured, along with the incidence of hypotensive episodes defined as mean blood pressure (MBP) fall?>?20mmHg, whether symptomatic or not. Subgroups of patients distributed according to age, baseline blood pressure (BP) and LVEF were subsequently analysed.

Results: Overall, a statistically significant treatment effect in favour of perindopril was observed. First-dose hypotension was observed more frequently following captopril than perindopril administration, with lower MAP minimal levels (78.0?±?8.9 vs. 84.5?±?10.1?mmHg, p?<?0.0001), greater maximum falls (17.6?±?8.3 vs. 12.8?±?7.3mmHg, p?<?0.0001) and more frequent hypotensive episodes (42% vs. 15%, p?<?0.0001). The incidence of at least one symptomatic episode was also significantly higher with captopril (10 patients vs. one patient, p?=?0.029). Subgroup analyses according to age (< 70 years or > 70 years) or LVEF (< 30% or > 30%) reflected the main result.

Conclusion: Initiation of treatment with ACE inhibitors is associated with different haemodynamic and clinical tolerances in CHF patients, regardless of their risk for hypotension, with possible clinical implications.     

Corneal endothelial changes in long-term cannabinoid users

Purpose: The aim of this study was at evaluating the effects of long-term cannabis use on the corneal endothelial cells with the specular microscopy.

Methods: The study enrolled 28 eyes of 28 patients diagnosed with cannabinoid use disorder. The cannabinoid group was selected among patients who had been using the substance for three days or more per week over the past one year. Thirty-two eyes of 32 age- and sex-matched healthy individuals enrolled as control group in the study. Corneal endothelial cell density (CD), coefficient of variation (CV) and hexagonal cell ratio (HEX) values were analyzed by specular microscopy.

Results: The mean CD was 2900?±?211 cells/mm² in the cannabinoid group and 3097?±?214 cells/mm² in the control group (p?p?>?0.05). No significant difference was present between the cannabinoid and the control groups in terms of mean CV value. The mean HEX was 52?±?5% in the cannabinoid group and 53?±?10% in the control group (p?>?0.05). There was not a significant difference between the cannabinoid and the control groups in terms of mean HEX value.

Conclusion: A significant decrease in CD was found in cannabinoid users compared the control group.     

Effects of triptolide on pharmacokinetics of fenofibrate in rats and its potential mechanism

1. Triptolide and fenofibrate are often used together for the treatment of nephrotic syndrome in Chinese clinics.

2. This study investigates the effects of triptolide on the pharmacokinetics of fenofibrate in rats and it potential mechanism.

3. The pharmacokinetics of fenofibrate (20?mg/kg) with or without triptolide pretreatment (2?mg/kg/day for seven days) were investigated. Additionally, the inhibitory effects of triptolide on the metabolic stability of fenofibrate were investigated using rat liver microsome incubation systems.

4. The results indicated that the C_max (35.34?±?7.52 vs. 30.43?±?6.45?μg/mL), t_1/2 (6.17?±?1.15 vs. 4.90?±?0.82?h) and AUC_(0–t) (468.12?±?35.84 vs. 416.35?±?32.68?mg?h?L^?1) of fenofibric acid decreased significantly (p?<?.05). The T_max of fenofibric acid increased significantly (p?<?.05) from 5.12?±?0.36 to 6.07?±?0.68?h. Additionally, the metabolic stability of fenofibrate was prolonged from 35.8?±?6.2 to 48.6?±?7.5?min (p?<?.05) with the pretreatment of triptolide.

5. In conclusion, these results indicated that triptolide could affect the pharmacokinetics of fenofibric acid, possibly by inhibiting the metabolism of fenofibrate in rat liver when they were co-administered.

     

Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes

ABSTRACT

Objective: Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.

Research design and methods: This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N?=?211) using insulin glargine (without mealtime insulin)?±?oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120?µg with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of ≥70 to <100?mg/dL.

Main outcome measures: Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.

Results: Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (?1.6?±?0.3?kg vs. +0.7?±?0.3?kg, p?<?0.001; mean?±?SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (?0.8?±?0.2?mg/L vs. 0.1?±?0.2?mg/L, p?<?0.01; mean?±?SE). Patients with baseline hsCRP?>?3?mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p?<?0.05). Patients with baseline triglycerides ≥150?mg/dL or ≥200?mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (?43?±?14?mg/dL or ?59?±?19?mg/dL; p?<?0.05; mean?±?SE) but not with placebo (1?±?29?mg/dLor ?3?±?54?mg/dL; mean?±?SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.

Conclusions: Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.     

Assessment of the therapeutic activity of a combination of almitrine and raubasine on functional rehabilitation following ischaemic stroke

Background and objectives: Stroke is a major cause of disability. Certain experimental studies have suggested that a combination of almitrine?+?raubasine (Duxil) increases the supply of oxygen to cerebral tissues and may be beneficial in post-stroke rehabilitation. This multicentre clinical study was carried out in order to assess the efficacy of this combination on post-stroke rehabilitation.

Methods: The trial was a randomised, double-blind, placebo-controlled study. Patients that had experienced an ischaemic cerebrovascular accident (confirmed by CT scan) were included 4-6 weeks after the acute onset and received randomised treatment of either almitrine?+?raubasine or placebo 2 tablets daily for 3 months. Before treatment, there was a 2-week washout period for stopping all other drugs, except for antihypertensive and antidiabetic drugs. We assessed the patients by Barthel Index (BI), Neurological Functional Deficit Scores (NFDS), and Hasagawa Dementia Scales (HDS) each month after treatment.

Results: A total of 83 patients were entered into the study and data were available for 74. Of these, 38 patients received almitrine?+?raubasine and 36 received placebo. The baseline characteristics were comparable between both groups. Almitrine?+?raubasine was significantly more effective than placebo at increasing BI at 1, 2 or 3 months (14.6?±?13.8 versus 3.3?±?13.2, p?=?0.01; 19.3?±?13.6 versus 8.8?±?14.0, p?=?0.02; 22.6?±?14.7 versus 10.7?±?17.0, p?=?0.02 respectively) and reducing NFDS at 1 month (3.6?±?3.2 versus 1.9?±?3.5, p?=?0.034) after treatment. More almitrine?+?raubasine-treated patients' NFDS had improved compared with placebo-treated patients at 2 and 3 months (97 versus 78%, p?=?0.013; 100 versus 86%, p?=?0.023 respectively). Compared with pre-treatment, there was a strong tendency towards an improvement of HDS with almitrine + raubasine. The number of adverse events reported was low for the almitrine + raubasine-treated group and the placebo group and all events were mild, of short duration and resolved without treatment. Almitrine + raubasine had no clinically significant effect on blood pressure, heart rate or other laboratory tests.

Conclusion:The results indicate that almitrine + raubasine can accelerate neurological function recovery after stroke to some degree and is well tolerated.     

Efficacy and Safety of Phospholipid Liposomes in the Treatment of Neuro-psychological Disorders Associated with the Menopause: A Double-blind,Randomised, Placebo-controlled Study

SUMMARY

A double-blind, randomised, placebo-controlled clinical trial was performed to evaluate the efficacy and safety of phospholipid liposomes (Liposom® Forte) administered parenterally in the treatment of anxiety and depression linked to the menopause.

A total of 64 females aged 40-60 years were randomised to receive the active drug or placebo intramuscularly; 58 patients completed the study. Treatment lasted 60 consecutive days. One IM administration of 2?ml active drug or placebo every other day was carried out.

Efficacy was evaluated by the Hamilton Anxiety Scale (HAMA) and the Climacteric Index. An intention-to-treat analysis was performed, defined as all patients administered with at least one dose of the study medications with at least one return visit.

A highly significant (p?<?0.001) decrease in) HAMA total score in both groups was noted. However, the decline in the HAMA score was significantly greater in patients administered phospholipid liposomes after 40 days (p?=?0.006), 60 days of treatment (p?<?0.001) and at the last follow-up visit (p?<?0.001). Also, there were statistically significant differences between treatment groups after 60 days of therapy for individual items, such as anxious mood (p?=?0.006), tension (p?=?0.024) and fear (p?=?0.009), with significantly less patients experiencing these symptoms in the phospholipid liposomes-treated group.

When the Climacteric Index was evaluated, a highly significant (p?<?0.001) decrease in the total score in both groups was noted. However, the decline was significantly greater in patients administered phospholipid liposomes after 40 days of treatment (p?=?0.017), 60 days of treatment (p?=?0.0013) and at the last follow-up visit (p?=?0.0012). Significant differences between treatment groups were recorded after 60 days in asthenia (p?=?0.05), dizziness (p?=?0.024) and restlessness (p?=?0.019) in favour of the active treatment.

Twelve patients reported at least one adverse event, nine in the phospholipid liposomes group

and three in the placebo group (p?=?0.062). The most commonly reported event was drowsiness with two reports in each group.

These findings further demonstrate that phospholipid liposomes administered intramuscularly are active against mild anxiety and depressive symptoms in menopausal women.     

Clinical efficacy of controlled-release oxycodone 20 mg administered on a 12-h dosing schedule on the management of postoperative pain after breast surgery for cancer

SUMMARY

Objective: To assess clinical efficacy of controlled-release oxycodone (CRO) 20?mg on a 12-h dosing schedule in this prospective, randomised, placebo-controlled, double-blinded study of 40 ASA physical status I-III women undergoing breast surgery for cancer.

Research design and methods: General anaesthesia using remifentanil and propofol was performed for surgery. Both groups received premedication with oral midazolam 7.5?mg 1?h before surgery. In the controlled-release oxycodone group, one tablet of 20?mg CRO was administered with the premedication, and 12?h after the premedication another 20?mg CRO. In the placebo (PL) group, a placebo tablet was administered with the premedication, and 12?h later another placebo tablet. All patients had access to opioid rescue medication via an IV patient-controlled analgesia (PCA) device.

Main outcome measures: Area under the curve (AUC), based on IV opioid rescue consumption over 24?h postoperatively.

Results: The AUC for IV PCA opioid consumption was significantly lower in the CRO group than in the PL group (p?=?0.01). The CRO group required less IV opioid loading dose (p?<?0.001), and consumed less opioid rescue medication 4h (p?=?0.036), 16h (p?=?0.01), and 24?h (p?=?0.005) postoperatively. AUC for VAS scores at rest was significantly lower in the CRO group than in the PL group (p?=?0.05). VAS scores at rest were lower in the CRO group 16?h (p?=?0.04) and 24h (p?=?0.03) postoperatively. There was no difference in AUC for pain scores on movement (p?=?0.103) and for quality of analgesia (p?=?0.139). There was no difference in nausea between groups (p?=?0.34). Pruritus, arterial hypotension or hypertension, bradycardia, and tachycardia were not observed in either treatment group. None of the patients showed signs of confusion, agitation, or respiratory depression.

Conclusion: The administration of CRO 20?mg on a 12-h dosing schedule halves postoperative IV PCA opioid consumption. CRO 20mg is effective in preventing pain after breast surgery for cancer with only mild side-effects.     

Epidemiology,clinical and economic outcomes of admission hyponatremia among hospitalized patients

ABSTRACT

Background: Hyponatremia, the most frequent electrolyte derangement identified among hospitalized patients, is associated with worsened outcomes in patients with pneumonia, heart failure and other disorders.

Research design and methods: We performed a retrospective cohort study of hospitalized patients to quantify the attributable influence of admission hyponatremia on hospital costs and outcomes. Data were derived from a large administrative database with laboratory components, representing 198,281 discharges from 39 US hospitals from January 2004 to December 2005. Hyponatremia was defined as admission serum [Na⁺]?<?135?mEq/L.

Results: The incidence of hyponatremia at admission was 5.5?%?(n?=?10,899). Patients with hyponatremia were older (65.7?±?19.6 vs. 61.5?±?21.8, p?<?0.001) and had a higher Deyo-Charlson Comorbidity Index score (1.8?±?2.1 vs. 1.3?±?1.8, p?<?0.001) than those with normal [Na⁺]. A higher proportion of hyponatremic patients required intensive care unit (ICU) (17.3?%?vs. 10.9?%?, p?<?0.001) and mechanical ventilation (MV) (5.0?%?vs. 2.8?%?, p?<?0.001) within 48?hours of hospitalization. Hospital mortality (5.9?%?vs. 3.0?%?, p?<?0.001), mean length of stay (HLOS, 8.6?±?8.0 vs. 7.2?±?8.2 days, p?<?0.001) and costs ($16,502?±?$28,984 vs. $13,558?±?$24,640, p?<?0.001) were significantly greater among patients with hyponatremia than those without. After adjusting for confounders, hyponatremia was independently associated with an increased need for ICU (OR 1.64, 95?%?CI 1.56–1.73) and MV (OR 1.68, 95?%?CI 1.53–1.84), and higher hospital mortality (OR 1.55, 95?%?CI 1.42–1.69). Hyponatremia also contributed an increase in HLOS of 1.0 day and total hospital costs of $2,289.

Conclusions: Hyponatremia is common at admission among hospitalized patients and is independently associated with a 55?%?increase in the risk of death, substantial hospital resource utilization and costs. Potential for bias inherent in the retrospective cohort design is the main limitation of our study. Studies are warranted to explore how prompt normalization of [Na⁺] may impact these outcomes.