A minimal physiologically based pharmacokinetic model for high-dose methotrexate.

Purpose: High-dose methotrexate (HDMTX) is administered for the treatment of a variety of malignant tumors. Wide intra- and inter-individual variabilities characterize the pharmacokinetics of MTX, which is mostly excreted renally. HDMTX dosages are prescribed as a function of body surface area whereas dose adjustments depending on renal function are not well defined.

A simplified math approach to predict ICU beds and mortality rate for hospital emergency planning under Covid-19 pandemic.

The different stages of Covid-19 pandemic can be described by two key-variables: ICU patients and deaths in hospitals. We propose simple models that can be used by medical doctors and decision makers to predict the trends on both short-term and long-term horizons. Daily updates of the models with real data allow forecasting some key indicators for decision-making (an Excel file in the Supplemental material allows computing them).

Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study.

Background And Objectives: Critically ill patients present reduced endogenous melatonin blood levels, and they might benefit from its exogenous supplementation. The aim of this research was to evaluate the feasibility of different routes of administration and drug formulations of melatonin. The efficiency of absorption was assessed as well as the adequacy in achieving and maintaining the physiological nocturnal blood peak.

Physiologically-based pharmacokinetic simulations in pharmacotherapy: selection of the optimal administration route for exogenous melatonin.

The benefits of melatonin on human body are drawing increasing attention from several researchers in different fields. While its role as cure for sleep disturbances (e.g.

A physiologically-based model to predict individual pharmacokinetics and pharmacodynamics of remifentanil.

Remifentanil based anesthesia is nowadays spread worldwide. This drug is characterized by a rapid onset of the analgesic effects, but also by a rapid onset of the side effects. For this reason, the knowledge of the remifentanil concentration in the human body is a key topic in anesthesiology.

A physiologically based model for tramadol pharmacokinetics in horses.

This work proposes an application of a minimal complexity physiologically based pharmacokinetic model to predict tramadol concentration vs time profiles in horses. Tramadol is an opioid analgesic also used for veterinary treatments. Researchers and medical doctors can profit from the application of mathematical models as supporting tools to optimize the pharmacological treatment of animal species.

Engineering approaches in siRNA delivery.

siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments.

Chemical Engineering in the "BIO" World.

Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level.

Innovations and Improvements in Pharmacokinetic Models Based on Physiology.

Background: Accompanied by significant improvements of modeling techniques and computational methods in medical sciences, the last thirty years saw the flourishing of pharmacokinetic models for applications in the pharmacometric field. In particular, physiologically based pharmacokinetic (PBPK) models, grounded on a mechanistic foundation, have been applied to explore a multiplicity of aspects with possible applications in patient care and new drugs development, as in the case of siRNA therapies.

Method: This article summarizes the features we recently introduced in PBPK modeling within a threeyear research project funded by Italian Research Ministry.

Neuropathy and levodopa in Parkinson's disease: evidence from a multicenter study.

The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥ 3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD).

The Viareggio LPG railway accident: event reconstruction and modeling.

This manuscript describes in detail the LPG accident occurred in Viareggio on June 2009 and its modeling. The accident investigation highlighted the uncertainty and complexity of assessing and modeling what happened in the congested environment close to the Viareggio railway station. Nonetheless, the analysis allowed comprehending the sequence of events, the way they influenced each other, and the different possible paths/evolutions.

Emergencies in parkinsonism: akinetic crisis, life-threatening dyskinesias, and polyneuropathy during L-Dopa gel treatment.

This article reviews literature on three emergencies in Parkinson's disease (PD): Akinetic crisis, severe dyskinesias or life-threatening dyskinesias, and polyneuropathy during duodenal L-Dopa gel infusion treatment. Akinetic crisis is also known as Parkinsonian hyperpyrexia, Neuroleptic-like malignant syndrome, Acute akinesia, and Malignant syndrome in parkinsonism. It appears in 0.

Restless legs syndrome in multiple sclerosis: a case-control study.

The aim of our study was to explore restless legs syndrome (RLS) frequency in multiple sclerosis (MS)-patients and establish whether RLS could be a symptom of MS. Over a period of 1 year, we consecutively enrolled 202 MS-patients and 212 healthy controls, matched for sex and age, in a case-control study. All of them filled in a structured questionnaire according to IRLSSG criteria.

Accidents involving liquids: a step ahead in modeling pool spreading, evaporation and burning.

The manuscript focuses on the modeling of industrial accidents involving liquid substances, i.e. liquid pools.

On pool spreading around tanks: geometrical considerations.

The paper discusses a straightforward approach for evaluating the distance covered by a spreading liquid pool, when the axisymmetric hypothesis is no longer valid. This distance is evaluated by a three-steps methodology: the pre-processing of input data (bund radius, if present, and radial velocity); the simulation of pool spreading by a model based on the axisymmetric hypothesis; and the post-processing of results. The paper reports some geometrical correlations to pre- and post-process the data, with regard to four case-studies.

Bed footboard peroneal and tibial neuropathy. A further unusual type of Saturday night palsy.

An uncommon cause of bilateral tibial and peroneal compression neuropathy is reported. After taking alcohol and drugs, a young heroin-addicted man lay unconscious overnight in supine position, with both legs crossing the wooden board at the end of the bed, the posterior aspect of the flexed knees pressing against its edge. The following day, he had weakness of foot flexion and extension and a sensory loss consistent with a bilateral tibial and peroneal neuropathy.

Electroneurography index based on nerve conduction study data: method and findings in control subjects.

We developed a summary score of data obtained from nerve conduction studies (NCS). The principle of such approach is that when a nonrandom trend to lower amplitudes or conduction velocities is present, it may be revealed by a summary nerve conduction score. In a group of normal subjects, peroneal, sural, ulnar, and superficial radial nerves were studied; age- and height-related F-wave and soleus H-reflex latencies were also examined.