Is There a Role for Growth and Differentiation Factor-15 in B-Cell Lymphoproliferative Neoplasms?

Growth and differentiation factor-15 (GDF-15) correlates with worse outcome of many tumours and any cause mortality. Data about its role in lymphoproliferative neoplasms (LPN) are scarce. Our research aimed to reveal the correlation between GDF-15 and standard laboratory parameters of LPN activity, and to get insight into the possible value of this cytokine assessment in lymphoma patients. Prospective research included 40 patients treated for aggressive or indolent LPN, and 31 with indolent LPN on "watch and wait" regimen. Analyses were performed before and after treatment in treated patients and on two separate occasions in the "watch and wait" group. ELISA technique with R&D assays according to the manufacturer manual, from stored sera at - 70 °C was used for GDF-15 level measurement. Statistical analyses were performed by IBM SPSS Statistics 22 using descriptive and inferential statistics. As appropriate, differences between groups were assessed by two tailed t-test, Mann-Whitney or x2 test. Spearman Rank Order Correlation was done to correlate GDF-15 with standard laboratory markers of disease activity. All tests are two-tailed with significance level p < 0. 05. GDF-15 (p = 0.028) and fibrinogen (p = 0.001) concentrations increased after treatment in indolent lymphoma patients while ß2 microglobulin decreased (p < 0.001). GDF-15 positively correlated with ß2microglobulin before (p < 0.001) and after (p = 0.031) therapy. There were no differences in any of the aforementioned parameters in the "watch and wait" group during observation. A positive correlation between GDF-15 and ß2 microglobulin in patients with indolent LPN who need treatment suggests potential value in risk assessment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01695-6.

Eculizumab for paroxysmal nocturnal hemoglobinuria: Two cases of successful pregnancy outcomes.

Paroxysmal nocturnal hemoglobinuria is a rare disease with the incidence ranging from 0.08 to 0.57 per 100,000 person-years. Up to 25% of cases in women are detected during pregnancy. We report two cases of successful pregnancy outcomes in patients treated with eculizumab, pointing out the importance of interdisciplinary approach in these high-risk pregnancies.

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.

Background: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets. Results: We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. Conclusions: These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry. Funding: This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1-190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016-0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 - 2056) (FXV). Clinical trial number: NCT03842800.

Ketamine is a widely used anesthetic as well as a popular illegal recreational drug. Recently, it has also gained attention as a potential treatment for depression, particularly in cases that don't respond to conventional therapies. However, individuals can vary in their response to ketamine. For example, the drug can alter some people's perception, such as seeing objects as larger or small than they are, while other individuals are unaffected. Although a single dose of ketamine was shown to improve depression symptoms in approximately 65% of patients, the treatment does not work for a significant portion of patients. Understanding why ketamine does not work for everyone could help to identify which patients would benefit most from the treatment. Previous studies investigating ketamine as a treatment for depression have typically included a group of individuals given ketamine and a group given a placebo drug. Assuming people respond similarly to ketamine, the responses in each group were averaged and compared to one another. However, this averaging of results may have masked any individual differences in response to ketamine. As a result, Moujaes et al. set out to investigate whether individuals show differences in brain activity and behavior in response to ketamine. Moujaes et al. monitored the brain activity and behavior of 40 healthy individuals that were first given a placebo drug and then ketamine. The results showed that brain activity and behavior varied significantly between individuals after ketamine administration. Genetic analysis revealed that different gene expression patterns paired with differences in ketamine response in individuals ­ an effect that was hidden when the results were averaged. Ketamine also caused greater differences in brain activity and behavior between individuals than other drugs, such as psychedelics, suggesting ketamine generates a particularly complex response in people. In the future, extending these findings in healthy individuals to those with depression will be crucial for determining whether differences in response to ketamine align with how effective ketamine treatment is for an individual.

Share of and Absolute Costs of Informal Care in Five Subpopulations of Outpatients with Dementia in Croatia: A Latent Profile Analysis.

BACKGROUND: High heterogeneity exists in estimates of the share of and absolute costs of informal care (IC) for individuals diagnosed with dementia. OBJECTIVE: To assess the differences in the share of and absolute costs of IC between subpopulations defined by latent profiles of activities of daily living (ADLs), neuropsychiatric symptoms, and global cognitive functioning. METHODS: We performed a nested cross-sectional analysis of data collected from 2019-2021 at the Zagreb-Zapad Health Center, Zagreb, Croatia, from a sample of patients and their caregivers. The outcome was the share of costs of IC in the total costs of care estimated using the Resource Utilization in Dementia questionnaire. We used latent profile analysis of six principal components of the Alzheimer's Disease Cooperative Study ADLs inventory, Neuropsychiatric Inventory and Mini-Mental State Examination, and conducted the analysis using beta and quantile regression. RESULTS: We enrolled 240 patients with a median age of 74 years; 78% were women. The annual cost for treatment and care for one patient was 11,462 (95% confidence interval 9,947; 12,976) EUR. After the adjustment for covariates, five latent profiles were significantly associated with the share of costs and absolute cost of IC. The adjusted annual costs of IC ranged from 2,157 EUR, with a share of 53% in the first latent profile, to 18,119 EUR, with a share of 78% in the fifth latent profile. CONCLUSION: The population of patients with dementia was heterogeneous, and there were relatively large differences in the share and absolute costs of IC between particular subpopulations.

Borderline and Depression: A Thin EEG Line.

In everyday clinical practice, there is an ongoing debate about the nature of major depressive disorder (MDD) in patients with borderline personality disorder (BPD). The underlying research does not give us a clear distinction between those 2 entities, although depression is among the most frequent comorbid diagnosis in borderline personality patients. The notion that depression can be a distinct disorder but also a symptom in other psychopathologies led our team to try and delineate those 2 entities using 146 EEG recordings and machine learning. The utilized algorithms, developed solely for this purpose, could not differentiate those 2 entities, meaning that patients suffering from MDD did not have significantly different EEG in terms of patients diagnosed with MDD and BPD respecting the given data and methods used. By increasing the data set and the spatiotemporal specificity, one could have a more sensitive diagnostic approach when using EEG recordings. To our knowledge, this is the first study that used EEG recordings and advanced machine learning techniques and further confirmed the close interrelationship between those 2 entities.

Changes in psychiatric services dynamics during the COVID-19 pandemic: Recognizing the need for resources shift.

With the significant impact of COVID-19 pandemic on the health, and the functioning of health care system, it has become increasingly important to understand changes in the ways health services were utilized and the factors influencing it. Drop in psychiatric admissions was seen during the pandemic, but also an increase in acute hospitalizations and emergency visits. Our aim was to analyze changes in out- and in-patient services utilization in the largest Croatian psychiatric institution during the first year of the pandemic, observed through the lens of the stringency index, and compare it to the pre-pandemic year. Along with an overall drop in hospitalizations, but a unit-specific rise in hospitalization, we have observed a non-significant overall drop in regular outpatient visits, and a significant drop coinciding with strictest epidemiological measures. There was also a significant increase in emergency visits coinciding with epidemiological measures that failed to return to pre-pandemic values, pointing to an expected significant and prolonged burden on emergency services. Simultaneous analysis of changing dynamics of mental health care service utilization during the pandemic helps us identify specific points of increased burden, and help us plan for early and flexible resources shift in order to adequately respond to evolving challenges.

Extraction of Bioactive Metabolites from Achillea millefolium L. with Choline Chloride Based Natural Deep Eutectic Solvents: A Study of the Antioxidant and Antimicrobial Activity.

In this study, the extraction efficiency of natural deep eutectic solvents (NADES) based on choline chloride as a hydrogen bond acceptor (HBA) and five different hydrogen bond donors (HBD; lactic acid, 1,4-butanediol, 1,2-propanediol, fructose and urea) was evaluated for the first time for the isolation of valuable bioactive compounds from Achillea millefolium L. The phytochemical profiles of NADES extracts obtained after ultrasound-assisted extraction were evaluated both spectrophotometrically (total phenolic content (TPC) and antioxidant assays) and chromatographically (UHPLC-MS and HPLC-UV). The results were compared with those obtained with 80% ethanol, 80% methanol, and water. The highest TPC value was found in the lactic acid-based NADES (ChCl-LA), which correlated with the highest antioxidant activity determined by the FRAP analysis. On the other hand, the highest antiradical potential against ABTS+• was determined for urea-based NADES. Phenolic acids (chlorogenic acid and dicaffeoylquinic acid isomers), flavones (luteolin and apigenin), and their corresponding glucosides were determined as the dominant individual phenolic compounds in all extracts. The antibacterial and antifungal properties of the extracts obtained against four bacterial cultures and two yeasts were evaluated using two methods: the agar dilution method to obtain the minimum inhibitory concentration (MIC) and the minimum bactericidal or fungicidal concentration (MBC or MFC), and the disc diffusion method. ChCl-LA had the lowest MIC and MBC/MFC with respect to all microorganisms, with an MIC ranging from 0.05 mg mL-1 to 0.8 mg mL-1, while the water extract had the weakest inhibitory activity with MIC and MBC/MFC higher than 3.2 mg mL-1.

100 Years apart: Psychiatric admissions during Spanish flu and COVID-19 pandemic.

The last pandemic comparable to the current COVID-19 pandemic was the Spanish flu. Using the admission record books for the years 1917 and 1918 and electronic health records for the years 2019 and 2020, we extracted the relevant data and explored how they affected the numbers of emergency psychiatric admissions. The general trend in both pandemics was that they did not cause a rise in psychiatric admissions, findings which go along with reports around Europe. The causes for these similarities are complex but provide an interesting perspective as to why there is no concurrent rise in emergency psychiatric admissions.

Changes in the physicochemical, antioxidant and antibacterial properties of honeydew honey subjected to heat and ultrasound pretreatments.

The objective of this study was to examine the effect of different treatments on the physicochemical, antioxidant, and antibacterial properties of honeydew honey. Honeydew honey was subjected to heat treatment and 9 different ultrasound treatments. Our results showed that the following parameters were significantly changed: water content, pH, electrical conductivity, diastase activity, HMF content and water activity. The ultrasound resulted in an increase in the total phenol content and the antioxidant capacity (DPPH, FRAP, and ABTS tests) in comparison with the conventional thermal technique. In most cases, the samples subjected to ultrasound improved the antibacterial activity; the heat treatment resulted in a significant reduction of the antibacterial activity, and sample 4 (ultrasound 30 °C, 5 min) showed the best antibacterial activity. The ultrasound treatment, especially at lower temperatures, represents a technique that enables the preservation and improvement of the biological properties of honeydew honey.

Mapping brain-behavior space relationships along the psychosis spectrum.

Difficulties in advancing effective patient-specific therapies for psychiatric disorders highlight a need to develop a stable neurobiologically grounded mapping between neural and symptom variation. This gap is particularly acute for psychosis-spectrum disorders (PSD). Here, in a sample of 436 PSD patients spanning several diagnoses, we derived and replicated a dimensionality-reduced symptom space across hallmark psychopathology symptoms and cognitive deficits. In turn, these symptom axes mapped onto distinct, reproducible brain maps. Critically, we found that multivariate brain-behavior mapping techniques (e.g. canonical correlation analysis) do not produce stable results with current sample sizes. However, we show that a univariate brain-behavioral space (BBS) can resolve stable individualized prediction. Finally, we show a proof-of-principle framework for relating personalized BBS metrics with molecular targets via serotonin and glutamate receptor manipulations and neural gene expression maps derived from the Allen Human Brain Atlas. Collectively, these results highlight a stable and data-driven BBS mapping across PSD, which offers an actionable path that can be iteratively optimized for personalized clinical biomarker endpoints.

Attachment and survival of bacteria on apples with the creation of a kinetic mathematical model.

The estimation of growth or inactivation of bacterial population in fruits during preservation and storage provides useful information for the improvement of the safety of fresh-cut fruits and vegetables. This paper addressed the attachment to the surface and the growth in the flesh of apple fruits of four bacterial cultures (Escherichia coli, Bacillus cereus, Staphylococcus aureus and Pseudomonas aeruginosa). The growth of the bacterial cultures in apple flesh was monitored at particular time intervals, and Gompertz parameters, i.e. maximum number of bacteria (Pm), the maximum growth rate of bacteria rp,m, and lag time tl, were used to determine the growth kinetics. After the immersion, the highest number of P. aeruginosa and the lowest number of B. cereus adhered to the apples. After washing and swabbing, E. coli was reduced from the surface of apples to the highest extent (by 3.34 log cfu g-1), while the number of B. cereus was reduced to the lowest extent (1.66 log cfu g-1). Fitted curves of the Gompertz model corresponded quite well to the measured values of the number of microorganisms with R2 = 0.92-0.98. The values of the standard error (0.17-0.37) and extremely low p values of the Fischer test (p < 0.0001) indicated strict dependence between the model predicted and the maximum population density. The predicted values of the maximum number of microorganisms (Pm) correspond almost exactly to the actual values. A similar conclusion can be drawn for the maximum growth rate of microorganisms (rp,m), with the measured value being slightly higher than predicted values.

Choline elevation in amygdala region at recovery indicates longer survival without depressive episode: a magnetic resonance spectroscopy study.

RATIONALE: Depression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates. OBJECTIVES: To determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy. METHODS: Forty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling. RESULTS: Twenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks' lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13-0.77). CONCLUSION: Cho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.

DNA Intercalating Near-Infrared Luminescent Lanthanide Complexes Containing Dipyrido[3,2-a:2',3'-c]phenazine (dppz) Ligands: Synthesis, Crystal Structures, Stability, Luminescence Properties and CT-DNA Interaction.

In order to create near-infrared (NIR) luminescent lanthanide complexes suitable for DNA-interaction, novel lanthanide dppz complexes with general formula [Ln(NO3)3(dppz)2] (Ln = Nd3+, Er3+ and Yb3+; dppz = dipyrido[3,2-a:2',3'-c]phenazine) were synthesized, characterized and their luminescence properties were investigated. In addition, analogous compounds with other lanthanide ions (Ln = Ce3+, Pr3+, Sm3+, Eu3+, Tb3+, Dy3+, Ho3+, Tm3+, Lu3+) were prepared. All complexes were characterized by IR spectroscopy and elemental analysis. Single-crystal X-ray diffraction analysis of the complexes (Ln = La3+, Ce3+, Pr3+, Nd3+, Eu3+, Er3+, Yb3+, Lu3+) showed that the lanthanide's first coordination sphere can be described as a bicapped dodecahedron, made up of two bidentate dppz ligands and three bidentate-coordinating nitrate anions. Efficient energy transfer was observed from the dppz ligand to the lanthanide ion (Nd3+, Er3+ and Yb3+), while relatively high luminescence lifetimes were detected for these complexes. In their excitation spectra, the maximum of the strong broad band is located at around 385 nm and this wavelength was further used for excitation of the chosen complexes. In their emission spectra, the following characteristic NIR emission peaks were observed: for a) Nd3+: 4F3/2 → 4I9/2 (870.8 nm), 4F3/2 → 4I11/2 (1052.7 nm) and 4F3/2 → 4I13/2 (1334.5 nm); b) Er3+: 4I13/2 → 4I15/2 (1529.0 nm) c) Yb3+: 2F5/2 → 2F7/2 (977.6 nm). While its low triplet energy level is ideally suited for efficient sensitization of Nd3+ and Er3+, the dppz ligand is considered not favorable as a sensitizer for most of the visible emitting lanthanide ions, due to its low-lying triplet level, which is too low for the accepting levels of most visible emitting lanthanides. Furthermore, the DNA intercalation ability of the [Nd(NO3)3(dppz)2] complex with calf thymus DNA (CT-DNA) was confirmed using fluorescence spectroscopy.

Long-Term Effectiveness and Cost Effectiveness of Multiple Myeloma Treatment Strategies for Elderly Transplant-Ineligible Patients in Serbia.

INTRODUCTION: Evidence on long-term effectiveness and cost effectiveness of treatment sequences for multiple myeloma (MM) is sparse. We used published data and country-specific data to assess the cost effectiveness of four-line treatment sequences for elderly transplant-ineligible patients with MM in Serbia. METHOD: We developed a Markov cohort model to compare long-term effectiveness and cost effectiveness of five sequential MM treatment alternatives from the perspective of the national healthcare provider. Effectiveness parameters on progression, mortality and adverse events were extracted from published clinical trials. Costs were based on price lists of the National Health Insurance Fund. We compared life expectancy, costs, and incremental cost-effectiveness ratios among alternative courses of action. The model was analyzed over a lifelong time horizon applying a 3% annual discount rate for effectiveness outcomes and costs. Robustness of the model was tested in multiple deterministic sensitivity analyses. RESULTS: The sequences were defined by the frontline treatment: MPT (melphalan-prednisone-thalidomide), MPV (melphalanprednisone-bortezomib), CTD (cyclophosphamide-thalidomide-dexamethasone), VCD (bortezomib-cyclophosphamidedexamethasone) and BP (bendamustine-prednisone). MPV sequence resulted in the highest remaining life expectancy (4.76 life years). Cost-effectiveness analysis resulted in three non-dominated strategies: MPT, VCD, and MPV sequences, with an incremental cost-effectiveness ratio of EUR 35,300 per life-year gained (LYG) for VCD and EUR 47,200/LYG for MPV relative to MPT. CONCLUSION: MPV sequence was the most effective in terms of life expectancy for elderly transplant-ineligible MM patients in Serbia. Bortezomib-based strategies would be recommended for the frontline treatment of patients with MM in Serbia if the willingness-to-pay threshold is around EUR 35,000-60,000/LYG.

Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells.

Inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) showed remarkable clinical efficacy in BRCA-mutated tumors. Based on the rational drug design, derivatives of PARP inhibitor 3-aminobenzamide (3-AB), 2-amino-4-methylbenzamide (L1) and 3-amino-N-methylbenzamide (L2), were coordinated to the ruthenium(II) ion, to form potential drugs affecting DNA and inhibiting PARP enzyme. The four conjugated complexes of formula: C1 [(ƞ6-toluene)Ru(L1)Cl]PF6, C2 [(ƞ6-p-cymene)Ru(L1)Cl]PF6, C3 [(ƞ6-toluene)Ru(L2)Cl2] and C4 [(ƞ6-p-cymene)Ru(L2)Cl2], have been synthesized and characterized. Colorimetric 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay showed the highest antiproliferative activity of C1 in HCC1937, MDA-MB-231, and MCF-7 breast cancer cells. Efficiency of inhibition of PARP-1 enzymatic activity in vitro decreased in order: C2 > C4 > 3-AB>C1 > C3. ICP-MS study of intracellular accumulation and distribution in BRCA1-mutated HCC1937 revealed that C1-C4 entered cells within 24 h. The complex C1 showed the highest intracellular accumulation, nuclear-targeting properties, and exhibited the highest DNA binding (39.2 ±â€¯0.6 pg of Ru per µg of DNA) that resulted in the cell cycle arrest in the S phase.

Language as a biomarker for psychosis: A natural language processing approach.

Human ratings of conceptual disorganization, poverty of content, referential cohesion and illogical thinking have been shown to predict psychosis onset in prospective clinical high risk (CHR) cohort studies. The potential value of linguistic biomarkers has been significantly magnified, however, by recent advances in natural language processing (NLP) and machine learning (ML). Such methodologies allow for the rapid and objective measurement of language features, many of which are not easily recognized by human raters. Here we review the key findings on language production disturbance in psychosis. We also describe recent advances in the computational methods used to analyze language data, including methods for the automatic measurement of discourse coherence, syntactic complexity, poverty of content, referential coherence, and metaphorical language. Linguistic biomarkers of psychosis risk are now undergoing cross-validation, with attention to harmonization of methods. Future directions in extended CHR networks include studies of sources of variance, and combination with other promising biomarkers of psychosis risk, such as cognitive and sensory processing impairments likely to be related to language. Implications for the broader study of social communication, including reciprocal prosody, face expression and gesture, are discussed.

Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives.

Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure - permeability and structure - retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.