Herpes simplex virus type 1 infection induces upregulation of interleukin-23 (p19) mRNA expression in trigeminal ganglia of BALB/c mice.

We investigated the expression kinetics of several cytokines in trigeminal ganglia (TG) and in brains of BALB/c mice during the course of ocular herpes simplex virus type 1 (HSV-1) infection. All mice recovered from the infection within 2 weeks. The quantitative rapid real-time RT-PCR method was used to analyze interleukin-4 (IL-4), interferon-gamma (IFN-gamma), IL-12p35, IL-12p40, and the recently described IL-23 (p19) mRNA in TG, brain, and splenocyte samples. In TG, we found elevated expression of mRNA for IL-23 (p19) from early acute infection (day 3) to the beginning of the latent phase (day 14). The increase was not detected in brain or in the spleen. IL-4 expression occurred in both TG and brain from the beginning of the experiment to the latent phase. During the latent phase (days 14 and 31), IL-4 expression was significantly elevated in the brain when compared with the uninfected controls (p < 0.05). Considerable expression of IFN-gamma mRNA was detected in TG of mice during acute HSV-1 infection. The expression of IL-23 was detected also in the brains of the mice, even though no significant changes were found during the acute HSV-1 infection. This is, to our knowledge, the first report to show elevated expression of IL-23 (p19) mRNA (p < 0.05) during viral infection in TG of mice.     

The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity

Aims

Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).

Methods

In this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20 mg day⁻¹ (n = 15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α-epoxycholesterol ratios were used as negative controls.

Results

Treatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference –0.069, –0.0067). The ratios of 25-hydroxycholesterol and 5α,6α-epoxycholesterol to cholesterol did not change.

Conclusions

The results establish atorvastatin as an inhibitor of CYP3A4 activity. Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including the conditions with altered cholesterol concentrations.     

Relative Efficacy of Sacubitril-Valsartan,Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis

Cardiovascular Drugs and Therapy - Sacubitril/valsartan, vericiguat, and the sodium-glucose co-transporter-2 inhibitors (SGLT2i) dapagliflozin and empagliflozin proved effective in phase 3 trials...     

Cardiovascular magnetic resonance for the diagnosis and management of heart failure with preserved ejection fraction

Heart Failure Reviews - Heart failure with preserved ejection fraction (HFpEF) is characterized by an impaired ventricular filling resulting in the development of dyspnea and other HF symptoms....     

Morphologies and prognostic significance of left ventricular volume/time curves with cardiac magnetic resonance in patients with non-ischaemic heart failure and left bundle branch block

The International Journal of Cardiovascular Imaging - Patients with non-ischaemic systolic heart failure (HF) and left bundle branch block (LBBB) can display a wide or narrow pattern (WP/NP) of the...     

Rosiglitazone treatment alleviates inflammation and improves liver function in overweight women with polycystic ovary syndrome: a randomized placebo-controlled study

In a randomized, placebo-controlled study, we studied the effects of 4 months' treatment with rosiglitazone on low-grade inflammation, liver function, lipid levels, and blood pressure in 30 overweight women with polycystic ovary syndrome. Rosiglitazone significantly decreased serum C-reactive protein levels, white blood cell count, and alanine aminotransferase enzyme activity but did not affect lipid or blood pressure levels. Placebo had no effect on any parameters.     

Baker and Itagliata's Quality of Life Scale in a group of 139 schizophrenic patients: factorial analysis and evaluation of global validity

The Satisfaction with Life Domains Scale SLDS published by Baker and Intagliata in 1982 and translated in French by Chambon and al. is one of the most used rating scales in the field of Subjective Quality of Life (SQL) for patients suffering from schizophrenia. It comprises 16 scales in 7 points and Likert format exploring the following fields: home/apartment/place of residence, neighbourhood, food, clothes, health, people they live with, friends, love life, relationships with their family, how they get on with other people, job/work day programming, spare time, what they do in the community for fun, services and facilities in their area, economic situation, general quality of life. In this study we present results on SLDS about 139 schizophrenic patients (108 males, 31 females) recruited in two centers Lyon (n = 41) and Saint-Etienne (n = 98). The SLDS was a part of more comprehensive studies including evaluation of needs for care, social support, delivery and costs of services. Diagnosis were confirmed using either the SCAN and CATEGO program (n = 108) or the list of the ICD-10 criteria (n = 31) applied at time of inclusion or on the basis of a representative episode of the illness. Patients were classified in two groups, the S group (S, n = 53) for those patients presenting clinical features at time of inclusion excepted residual forms (F 20.5) and the non S group (N-S, n = 86) for those patients free of symptoms at the time of assessment. Non parametric statistics (U test and Kendall test) were used for comparisons between groups. The field by field comparison of the scores shows the poorest level of SQL for love life (m = 4.2; sd = 1.8) and economic status (m = 4.4; sd = 1.8). Comparisons between S and non-S groups show an average range systematically higher for the non-S group and significant differences for the following fields: food, friends, how they get on with other people. The same comparisons between males and females show no significant differences excepted for the following fields: love life, economic situation. Principal components analysis with Varimax rotation were performed and a 4 factors solution was considered as the best one. Before rotation the first factor accounts for 31% of the variance and comprises all the items with loading higher than 0.4 allowing us to consider the possibility of a global score. This global score is normally distributed (m = 95.1 sd = 17.3) and shows a significant difference between S and non S-groups (S m = 92.2 sd = 20.1; non S m = 99.6 sd = 15.4 p = .02) but not between centers and between males and females. After rotation the first factor comprises relationships with family, how they get on with other people, job/work/day programming, spare time, what they do for fun and life in general. The hypothesis of unidimensionality of QV has to be tested using the RASCH model.