Pitavastatin in cardiometabolic disease: therapeutic profile

Statins effectively lower low-density lipoprotein-cholesterol (LDL-C) and reduce cardiovascular risk in people with dyslipidemia and cardiometabolic diseases such as Metabolic syndrome (MetS) or type 2 diabetes (T2D). In addition to elevated levels of LDL-C, people with these conditions often have other lipid-related risk factors, such as high levels of triglycerides, low levels of high-density lipoprotein-cholesterol (HDL-C), and a preponderance of highly atherogenic, small, dense low-density lipoprotein particles. The optimal management of dyslipidemia in people with MetS or T2D should therefore address each of these risk factors in addition to LDL-C. Although statins typically have similar effects on LDL-C levels, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects, adverse event profiles and drug-drug interactions. The choice of statin should therefore depend on the characteristics and needs of the individual patient. Compared with other statins, pitavastatin has distinct pharmacological features that translate into a broad range of actions on both apolipoprotein-B-containing and apolipoprotein-A-containing lipoproteins. Studies show that pitavastatin 1 to 4 mg is well tolerated and significantly improves LDL-C and triglyceride levels to a similar or greater degree than comparable doses of atorvastatin, simvastatin or pravastatin, irrespective of diabetic status. Moreover, whereas most statins show inconsistent effects on HDL-C levels, pitavastatin-treated patients routinely experience clinically significant elevations in HDL-C that are maintained and even increased over the long term. In addition to increasing high-density lipoprotein quantity, pitavastatin appears to improve high-density lipoprotein function and to slow the progression of atherosclerotic plaques by modifying high-density lipoprotein-related inflammation and oxidation, both of which are common in patients with MetS and T2D. When choosing a statin, it is important to note that patients with MetS have an increased risk of developing T2D and that some statins can exacerbate this risk via adverse effects on glucose regulation. Unlike many statins, pitavastatin appears to have a neutral and even beneficial effect on glucose regulation, making it a useful treatment option in this high-risk group of patients. Together with pitavastatin’s beneficial effects on the cardiometabolic lipid profile and its low potential for drug-drug interactions, this suggests that pitavastatin might be a useful lipid-lowering option for people with cardiometabolic disease.     

Wastewater: A Potential Bioenergy Resource

Wastewaters are a rich source of nutrients for microorganisms. However, if left unattended the biodegradation may lead to severe environmental hazards. The wastewaters can thus be utilized for the production of various value added products including bioenergy (H₂ and CH₄). A number of studies have reported utilization of various wastewaters for energy production. Depending on the nature of the wastewater, different reactor configurations, wastewater and inoculum pretreatments, co-substrate utilizations along with other process parameters have been studied for efficient product formation. Only a few studies have reported sequential utilization of wastewaters for H₂ and CH₄ production despite its huge potential for complete waste degradation.     

Ethylene and IAA interactions in the inhibition of photoperiodic flower induction of <Emphasis Type="Italic">Pharbitis nil</Emphasis>

It has been shown that both IAA and ethylene application inhibit flower induction in the short-day plant Pharbitis nil. However application of IAA has elevated ethylene production in this plant, as well. Strong enhancement of ethylene production is also correlated with the night-break effect, which completely inhibits flowering. In order to determine what the role of IAA and ethylene is in the photoperiodic flower induction in Pharbitis nil, we measured changes in their levels during inductive and non-inductive photoperiods, and the effects of ethylene biosynthesis and action inhibitors on inhibition of flowering by IAA. Our results have shown that the inhibitory effect of IAA on Pharbitis nil flowering is not physiological but is connected with its effect on ethylene biosynthesis.     

INFOS: spectrum fitting software for NMR analysis

Software for fitting of NMR spectra in MATLAB is presented. Spectra are fitted in the frequency domain, using Fourier transformed lineshapes, which are derived using the experimental acquisition and processing parameters. This yields more accurate fits compared to common fitting methods that use Lorentzian or Gaussian functions. Furthermore, a very time-efficient algorithm for calculating and fitting spectra has been developed. The software also performs initial peak picking, followed by subsequent fitting and refinement of the peak list, by iteratively adding and removing peaks to improve the overall fit. Estimation of error on fitting parameters is performed using a Monte-Carlo approach. Many fitting options allow the software to be flexible enough for a wide array of applications, while still being straightforward to set up with minimal user input.     

Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations

How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncover the fitness landscape defined by gene expression levels. We found strong antagonism and sign epistasis between these beneficial mutations. Mutations with the largest individual benefit interacted the most antagonistically with other mutations, a trend we also uncovered through analyses of datasets from other model systems. However, these beneficial mutations interacted multiplicatively (i.e., no epistasis) at the level of enzyme expression. By generating a model that predicts fitness from enzyme levels we could explain the observed sign epistasis as a result of overshooting the optimum defined by a balance between enzyme catalysis benefits and fitness costs. Knowledge of the phenotypic landscape also illuminated that, although the fitness peak was phenotypically far from the ancestral state, it was not genetically distant. Single beneficial mutations jumped straight toward the global optimum rather than being constrained to change the expression phenotypes in the correlated fashion expected by the genetic architecture. Given that adaptation in nature often results from optimizing gene expression, these conclusions can be widely applicable to other organisms and selective conditions. Poor interactions between individually beneficial alleles affecting gene expression may thus compromise the benefit of sex during adaptation and promote genetic differentiation.     

Insulin-induced expression of human heat-shock protein gene hsp70

In human hepatoma cell line Hep3B/T2, the human heat-shock-inducible gene hsp70 could be induced by insulin. The dose-dependent insulin effect correlates very well with the dissociation constant of the insulin receptor, indicating that the insulin effect is mediated by the insulin receptor. The expression of hsp70 gene was neither significantly induced by growth factors of epidermal and platelet-derived growth factors, nor by tumor promoter, calcium ionophore, cAMP, and glucocorticoids. These results indicate that the induction of expression of hsp70 gene by insulin is very specific and not cell cycle-related. Furthermore, the insulin-induced expression of hsp70 gene is transient, occurring specifically from 4 to 8 h after insulin addition.     

Percutaneous closure of a patent foramen ovale after cryptogenic stroke

A patent foramen ovale is a common intracardiac finding that is located between the left and right atrium. It can cause right-to-left shunting and has a high prevalence in patients who suffer a cryptogenic stroke. Earlier trials did not show superiority of percutaneous patent foramen ovale closure with standard medical therapy over standard medical therapy alone in the treatment of cryptogenic stroke. Interestingly, several meta-analyses show positive results regarding closure, suggesting underpowering of the individual trials. Recently, two large prospective trials and one long-term follow-up study showed benefit of percutaneous closure over standard medical therapy in treatment of cryptogenic stroke. A larger right-to-left shunt or the presence of an atrial septal aneurysm were predictors for a recurrent event. Therefore, percutaneous patent foramen ovale closure after cryptogenic stroke should be recommended over antiplatelet therapy alone in patients younger than 55 years of age with a high-risk patent foramen ovale.