Pharmacokinetic/ pharmacodynamic evaluation of anti-infective agents

Pharmacokinetic/pharmacodynamic modeling has become an extremely important tool in evaluating and optimizing anti-infective therapy. By systematically linking the pharmacokinetic and pharmacodynamic properties of the anti-infective agent, it is possible to make educated decisions about the correct drug to be used, correct dosing regimen and to estimate the probability of success with the selected dose regimen. This article gives an overview of the current pharmacokinetic/pharmacodynamic approaches for anti-infective agents and discusses their use in optimizing drug therapy.     

Blood-Brain Barrier Permeability of Asiaticoside,Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model

Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (P_app) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10^?6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.     

Diffusion‐weighted MRI monitoring of pancreatic cancer response to radiofrequency heat‐enhanced intratumor chemotherapy

The aim of this study was to evaluate the feasibility of using diffusion‐weighted MRI to monitor the early response of pancreatic cancers to radiofrequency heat (RFH)‐enhanced chemotherapy. Human pancreatic carcinoma cells (PANC‐1) in different groups and 24 mice with pancreatic cancer xenografts in four groups were treated with phosphate‐buffered saline (PBS) as a control, RFH at 42 °C, gemcitabine and gemcitabine plus RFH at 42 °C. One day before and 1, 7 and 14 days after treatment, diffusion‐weighted MRI and T₂‐weighted imaging were applied to monitor the apparent diffusion coefficients (ADCs) of tumors and tumor growth. MRI findings were correlated with the results of tumor apoptosis analysis. In the in vitro experiments, the quantitative viability assay showed lower relative cell viabilities for treatment with gemcitabine plus RFH at 42 °C relative to treatment with RFH only and gemcitabine only (37 ± 5% versus 65 ± 4% and 58 ± 8%, respectively, p < 0.05). In the in vivo experiments, the combination therapy resulted in smaller relative tumor volumes than RFH only and chemotherapy only (0.82 ± 0.17 versus 2.23 ± 0.90 and 1.64 ± 0.44, respectively, p = 0.003). In vivo, 14‐T MRI demonstrated a remarkable decrease in ADCs at day 1 and increased ADCs at days 7 and 14 in the combination therapy group. The apoptosis index in the combination therapy group was significantly higher than those in the chemotherapy‐only, RFH‐only and PBS treatment groups (37 ± 6% versus 20 ± 5%, 8 ± 2% and 3 ± 1%, respectively, p < 0.05). This study confirms that it is feasible to use MRI to monitor RFH‐enhanced chemotherapy in pancreatic cancers, which may present new options for the efficient treatment of pancreatic malignancies using MRI/RFH‐integrated local chemotherapy. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparative study of wavelet denoising in myoelectric control applications

Here, the wavelet analysis has been investigated to improve the quality of myoelectric signal before use in prosthetic design. Effective Surface Electromyogram (SEMG) signals were estimated by first decomposing the obtained signal using wavelet transform and then analysing the decomposed coefficients by threshold methods. With the appropriate choice of wavelet, it is possible to reduce interference noise effectively in the SEMG signal. However, the most effective wavelet for SEMG denoising is chosen by calculating the root mean square value and signal power values. The combined results of root mean square value and signal power shows that wavelet db4 performs the best denoising among the wavelets. Furthermore, time domain and frequency domain methods were applied for SEMG signal analysis to investigate the effect of muscle-force contraction on the signal. It was found that, during sustained contractions, the mean frequency (MNF) and median frequency (MDF) increase as muscle force levels increase.     

The Effectiveness and Safety of Platelet-Rich Plasma for Chronic Wounds: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.Patients and MethodsWe searched multiple databases from database inception to June 11, 2020, for randomized controlled trials and observational studies that compared PRP to any other wound care without PRP in adults with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.ResultsWe included 20 randomized controlled trials and five observational studies. Compared with management without PRP, PRP therapy significantly increased complete wound closure in lower-extremity diabetic ulcers (relative risk, 1.20; 95% CI, 1.09 to 1.32, moderate strength of evidence [SOE]), shortened time to complete wound closure, and reduced wound area and depth (low SOE). No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower-extremity venous ulcers or pressure ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. There was no statistically significant difference in adverse events.ConclusionAutologous PRP may increase complete wound closure, shorten healing time, and reduce wound size in individuals with lower-extremity diabetic ulcers. The evidence is insufficient to estimate an effect on wound healing in individuals with lower-extremity venous ulcers or pressure ulcers.Trial RegistrationPROSPERO Identifier: CRD42020172817     

New roles for mean platelet volume measurement in the clinical practice?

Several hundreds of studies recently investigated mean platelet volume (MPV) as measured by electronic cell counters in a wide variety of acquired diseases, and most of them found that platelet size was significantly increased with respect to healthy subjects. On this basis, it has been suggested that MPV can be used for diagnostic purposes. Moreover, investigation of subjects with arterial thrombosis not only revealed that their platelets were larger than those of controls, but also found that a high MPV predicted poor prognosis. Despite the large amount of available data, the pathogenesis of increased platelet size in these conditions is unclear. In particular, we do not know whether the increased platelet size is the cause or the consequence of thrombosis. Differences in MPV between patients and controls are usually very small and they reach the statistical significance because of the large number of investigated patients and the standardized methodology for MPV measurement. In real life, the wide variability of MPV possibly due to platelet count, sex, age, and ethnicity, as well as the very poor standardization of the methodologies used for MPV measurement, makes it impossible to decide whether an individual patient has normal or instead slightly increased MPV. So, MPV has presently no role in making diagnosis and defining prognosis in any acquired illness.     

More than skin deep

We present the case of a woman in her 50s with past medical history significant for psoriasis treated with methotrexate on a stable dose for the past 20?years, diabetes mellitus and chronic kidney disease. In the setting of a long flight, dehydration and non steroidal anti-inflammatory drug consumption, the patient presented to the emergency department with oral mucositis and cutaneous erosions and ulcers of the psoriasis plaques. MTX levels were normal corroborated by three different measurements in 24?h. Initially the complete blood count tests were significant for macrocytic, thrombocytopenia (82.000 10³/L) and impaired kidney function. The patient was diagnosed of acute methotrexate toxicity and started on intravenous folinic acid. In 24?h the patient developed severe pancytopenia. She required treatment with colony-stimulating factors, platelet and blood transfusions. After 10?days, the CBC improved to normal levels and the cutaneous lesions resolved.