The differential effects of neuroleptic drugs and PACAP on the expression of BDNF mRNA and protein in a human glioblastoma cell line

It has been suggested that, in addition to modulation of monoaminergic neurotransmission, antipsychotic drugs can also affect expression of neurotrophic factors in the brain. The present study was aimed to examine the effects of the first generation neuroleptic drug (FGA; haloperidol) and second generation neuroleptic drugs (SGAs; olanzapine and amisulpride) on expression and level of brain-derived neurotrophic factor (BDNF) in astrocyte-like T98G glioblastoma cell line. Effects of these drugs were compared to the action of PACAP38, a neuropeptide with well known BDNF-mediated neuroprotective effects. The tested neuroleptics differentially regulated the mRNA expression and protein level of BDNF depending on the concentration and incubation time. Using rtPCR technique, we demonstrate that, from the three tested neuroleptics, both haloperidol as well as olanzapine at 5 μM concentration (but not at 20 μM) increased BDNF mRNA expression with a similar efficacy after a 72 h incubation. In order to confirm the observed changes in the mRNA expression of BDNF, a protein expression assay was performed. The exposure of cells only to 5 μM olanzapine for 72 h increased BDNF concentration in the culture medium by 29%. Additionally, PACAP significantly up-regulated BDNF mRNA expression in T98G cells and the obtained results correlated positively with the increased production of BDNF protein, by 22% above control. The results of the paper show that olanzapine, similarly to exogenous PACAP38, increased BDNF mRNA expression and protein release, which can contribute to its neuroprotective mechanism of action in the cells of nonneuronal origin. The results of the present paper confirm the findings that BDNF may represent the key target for olanzapine and PACAP

Concomitant Administration of Different Doses of Simvastatin with Ivabradine Influence on PAI-1 and Heart Rate in Normo- and Hypercholesterolaemic Rats

Ivabradine is a novel heart rate lowering agent that inhibits If ionic current in the sinus node and demonstrates antiischaemic and antianginal activity. The aim of the paper was to investigate the effect its dose-dependent drug-drug interaction with simvastatin inhibitor HMGCo-A has on PAI-1 blood level, heart rate and blood pressure. The experiments were performed in hyper- and normocholesterolemic Wistar rats receiving simvastatin (1 and 20 mg × kg−1 bw) with ivabradine (10 mg × kg−1 bw) during a 4-week period. Ivabradine exacerbated the decrease of PAI-1 in normocholesterolemic animals receiving simvastatin at a dose of 1 mg/kg bw and was not observed to have any significant influence on the PAI-1 values in rats receiving 20 mg × kg−1 bw simvastatin. Ivabradine, coadministered with simvastatin given at a dose of 20 mg × kg−1 bw, significantly slowed the heart rate in normocholesterolaemic and hypercholesterolaemic groups as compared to the group receiving ivabradine alone. Conclusion. The administration of ivabradine to normocholesterolaemic and hypercholesterolaemic rats receiving simvastatin significantly exacerbated the slowing of heart rate with no effect on blood pressure. The administration of ivabradine has been shown to demonstrate different effects on PAI-1 values depending on lipid disorders

Rosuvastatin, sildenafil and their combination in monocrotaline-induced pulmonary hypertension in rat

There is considerable interest in the pleiotropic effects of statins and their potential role in the treatment of pulmonary hypertension. Previous experimental findings indicate that a combination of lipophilic statins with phosphodiesterase type-5 inhibitor, sildenafil, can offer preventive effects on rat monocrotaline-induced pulmonary hypertension. The present study is aimed to assess whether therapeutic regimen provides any benefits. Seven days after pulmonary hypertension induction, hydrophilic rosuvastatin and sildenafil were given 14 days to male Wistar outbred rats. Right ventricular pressure, right ventricle mass and three biomarkers were evaluated after 21 days: brain natriuretic peptide, high-density lipoprotein cholesterol and vascular endothelial growth factor. The present study demonstrates that administration of hydrophilic statin with sildenafil results in reduction of pulmonary vascular remodeling and right ventricular pressure. The results of biochemical measurements may suggest that statins play a positive role in right ventricle function or the process of angiogenesis in pulmonary hypertension development

New Medicine Service as support for medication adherence by chronically ill patients

Effective management of the treatment for chronically ill patients is a multifactorial process. The crucial is an accurate diagnosis, appropriate and well-designed pharmacotherapy, as well as patient medication adherence. Adherence is defined as the extent to which patients are able to follow the general practitioner's recommendations for the prescribed treatments. Patients’ reasons for deviating from the treatment plan are diverse and may be intentional or unintentional. They may be non-adherent during different stages of their treatment. Some patients may decide not to fill physician prescriptions and not start their treatment at all. Patients may use more or less than the prescribed medication or use their treatments at the wrong time. They may also discontinue therapy prematurely. The common reasons for medication non-adherence may include lack of symptoms, improvement in health, in patients’ subjective opinion, fear of potential side effects, long-term conditions, multimorbidity, and polypharmacy. Poor knowledge about medicines can also lead to severe consequences such as non-adherence. Several interventions may contribute to improved adherence. The current legislation in pharmaceutical care enables registered pharmacists to intervene successfully when a medicine is prescribed, increase effective medicine taking for the treatment of a long-term condition, and optimize the therapy; they also may offer the patient, opportunistic advice on healthy living or public health topics in line with the promotion of healthy lifestyles. One of the proposed pharmaceutical care services for Polish patients – the New Medicine Service, was introduced in England in 2011 as support for subjects starting a newly initiated medication for long-term treatment. The article presents the assumptions and goals for this pharmaceutical consultation in polish system of health care, discusses the interview schedule and forms, and describes the service's beneficial contribution to better medication adherence by chronically ill patients

The influence of different exercise training programs on the condition of animals with PH (<i>n = 1470 animals</i>).

Kaplan-Meier curves demonstrate the significant differences in overall survival among particular study groups (Pn = 266 animals); the mortality of animals with pulmonary hypertension from sedentary groups was higher than those subjected to exercise training (P = 0.0002) (A); early training protocol did not improve survival significantly (P>0.05) as compared to these subjects with PH that were exposed to the late training program (B), animals developed PH due to injection of monocrotaline (A − B); tree-plots show that training animals were characterized with significantly better exercise endurance (Q = 4.2; df = 1; P = 0.04) and weaker PH development (Q = 4.3; df = 1; P = 0.039) as compared to their sedentary counterparts (C, E); early training programs yielded benefits in relation to exercise endurance (Q = 16.7; df = 1; PD, F). The overall effect was expressed as response ratio (R), according to alterations in both heamodynamic (RVSP, mPAP) and remodeling parameters (Fulton index, PA muscularization), as well as animal exercise capacity. Increased values of response ratio (R) reveal worsening of PH-related parameters and better exercise endurance (C–F). A statistically significant Q measure (P<0.05) indicates heterogeneity among two or more analyzed subgroups.</p

The influence of some methodological items that characterize training programs on the resulting exercise endurance of animals with PH and disease development (n = 753 animals).

The overall effect was expressed as response ratio (R), according to alterations in both hemodynamic (RVSP, mPAP) and remodeling parameters (Fulton index, PA muscularization), as well as animal exercise capacity. The increased response ratio (R) values reveal worsening of PH-related parameters and better exercise endurance. A statistically significant Q measure (PA); and when the training intensity was adjusted to VO2max parameter, assessed individually (Q = 11.8; df = 1; P = 0.0006) (C); increasing intensity and slope were also related to less development of PH-related parameters in training subjects (Q = 16.1; df = 1; PB); any significant impact of individually matched training program (adjustment to VO2max) was not denoted for PH development (D).</p

Summary of risk of bias adopted from Hooijmans et al (2014) [4].

Summary of risk of bias adopted from Hooijmans et al (2014) [4].</p

The performance of animals with pulmonary hypertension in relation to methods used for the assessment of animal exercise capacity.

The overall effect was expressed as response ratio (R), according to alterations in both hemodynamic (RVSP, mPAP) and remodeling parameters (Fulton index, PA muscularization), as well as animal exercise capacity. The increased values of response ratio (R) reveal better exercise endurance (n = 1955 animals). A statistically significant Q measure (P124 comparisons) demonstrates that worsening of PH-related parameters was significantly correlated with poorer animal exercise capacity (P = 0.0001) (A); the method chosen for the exercise tests had no influence on the resultant changes in exercise capacity (Q = 0.59; df = 2; P>0.05) (B); among a wide range of parameters that could be detected in the analyzed experiments, a similar exercise capacity (C) was observed where the following sets of parameters were considered: distance, time to exhaustion and percentage exercise capacity (Q = 2.1; df = 2; P>0.05) or values of VO2max and time to VO2max (Q = 0.19; df = 1; P>0.05).</p

Summary of potential mechanisms underlying the beneficial effects of chronic exercise training in animal models of pulmonary hypertension.

Summary of potential mechanisms underlying the beneficial effects of chronic exercise training in animal models of pulmonary hypertension.</p

Study references.

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