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PubMed1989

Blood-brain barrier permeability to sodium. Modification by glucose or insulin?

In order to explore the pathogenetic mechanism underlying the changes in blood-brain barrier sodium transport in experimental diabetes, the effects of hyperglycemia and of hypoinsulinemia were studied in nondiabetic rats. In untreated diabetes, the neocortical blood-brain barrier permeability for sodium decreased by 20% (5.6 +/- 0.7 versus 7.0 +/- 0.8 X 10(5) ml/g/s) as compared to controls. Intravenous infusion of 50% glucose for 2 h was associated with a decrease in the blood-brain barrier permeability to sodium (5.4 +/- 1.2 X 10(5) ml/g/s), whereas rats treated with an inhibitor of insulin-secretion (SMS 201-995, a somatostatin-analogue) had normal sodium permeability (7.3 +/- 2.0 X 10(5) ml/g/s). Acute insulin treatment of diabetic rats normalized the sodium permeability within a few hours as compared to a separate control group (7.7 +/- 1.1 versus 6.9 +/- 1.4 X 10(5) ml/g/s). To elucidate whether the abnormal blood-brain barrier passage is caused by a metabolic effect of glucose or by the concomitant hyperosmolality, rats were made hyperosmolar by intravenous injection of 50% mannitol. Although not statistically significant, blood-brain barrier sodium permeability increased in hyperosmolar rats as compared to the control rats (8.3 +/- 1.0 and 7.0 +/- 1.9 X 10(5) ml/g/s, respectively). It is concluded that either hyperglycemia per se or a glucose metabolite is responsible for the blood-brain barrier abnormality which occurs in diabetes. Further, we suggest that the specific decrease of sodium permeability could be the result of glucose-mediated inhibition of the Na+K+-ATPase localized at the blood-brain barrier.

Animals↗
PubMed1998

Corticosteroid therapy augments gastroduodenal permeability to sucrose.

OBJECTIVE: The aim of the present study was to investigate whether corticosteroid therapy alters gastroduodenal mucosal permeability and whether permeability alteration is associated with macroscopic mucosal damage. METHODS: Eight patients taking oral corticosteroid therapy (total prednisone-equivalent dose, 1.5+/-0.1 g; duration, approximately 30 days), nine patients with multiple sclerosis taking high-dose intravenous methyl-prednisolone therapy (total dose, 11.7+/-0.5 g; duration, approximately 9 days), and 20 age- and gender-matched controls were studied. Gastroduodenal permeability was determined using sucrose as a site-specific permeability probe. Five-hour urine was collected after ingesting 100 g of sucrose and its urinary excretion rate was measured using high-pressure liquid chromatography. Gastroduodenal endoscopy was performed before steroid therapy to exclude subjects with evidence of macroscopic mucosal lesions. The sucrose test and endoscopy were repeated after completion of corticosteroid therapy. RESULTS: The urinary sucrose excretion rates were similar in the control group and in patient groups before corticosteroid therapy. The median excretion rate of sucrose increased four (one to 28)- and eight (two to 35)-fold, respectively, as compared with pretreatment values in patients taking oral steroid and high-dose intravenous methyl-prednisolone therapy (p < 0.01). Considering all patients together, subjects who received a mean prednisone-equivalent dose of 8.4+/-1.5 g exhibited mucosal lesions, whereas patients who received 3.3+/-1.8 g did not (p = 0.06). The post-therapy increments in sucrose excretion rates were associated with neither the presence of macroscopic lesions nor with the total steroid dose received. CONCLUSIONS: Corticosteroid therapy augments gastroduodenal permeability and high doses are associated with macroscopic mucosal lesions. Steroid-induced permeability increase does not appear to be associated with the presence of macroscopic mucosal lesions.

Administration, Oral↗
PubMed1998

The effects of Pain-Free Desensitizer on dentine permeability and tubule occlusion over time, in vitro.

The purpose of this in vitro study was to evaluate the efficacy of a new resin emulsion (Pain-Free Desensitizer) treatment for dentine hypersensitivity, for its ability to decrease dentine permeability. Crown segments were prepared from extracted, unerupted human 3rd molars by horizontal sectioning to remove occlusal enamel and the roots. The specimens were allocated in one of two groups: In group 1, the dentine surface was acid-etched to simulate the patent tubules of hypersensitive dentine. In group 2, the mineralized dentine surface was polished free of smear layer using a hydroxyapatite paste and ultrasonication. The hydraulic conductance of each specimen was then measured to obtain a pretreatment of control value. After a single treatment with resin desensitizer, the permeability was remeasured at 5 min, 1 day, 1 week and 1 month. Between measurements, the specimens were stored in buffer solution to simulate the solubilizing effects of saliva. Parallel specimens were followed by SEM examination. The results showed that a single treatment with resin desensitizer produced large, immediate, reductions in dentine permeability in both acid-etched and mineralized surfaces. In the acid-etched (group 1) specimens, the permeability returned to control values within 7 days, while the permeability of the group 2 specimens remained low even after 30 days of soaking. This simple treatment for occluding dentinal tubules may provide sufficient temporary reduction in dentine permeability to permit the development of natural desensitization.

Analysis of Variance↗
PubMed1998

Intestinal permeability in patients with acute myeloid leukemia.

Intestinal permeability was studied in patients with acute myeloid leukemia (AML) before, during and after chemotherapy. Intestinal permeability was determined by the lactulose (La)/mannitol (Ma) absorption test in 16 adult patients with de novo AML. The hydrogen breath test was used to disclose bacterial fermentation of the test substances in the small intestine. The permeability was found significantly increased (p<0.02) in the patients before induction chemotherapy treatment. During induction treatment and throughout the cytopenic period the intestinal permeability was constantly and significantly increased, compared with controls. In patients with abnormally increased permeability, no increase in hydrogen breath test result was noted. From our results it can be concluded that increased intestinal permeability is present in AML patients before commencing chemotherapy. Factors other than chemotherapy would seem to be more important regarding the occurrence of intestinal disturbances in these patients.

Acute Disease↗
PubMed2005

Degree of conversion and permeability of dental adhesives.

The aim of this study was to analyse the extent of polymerization of different adhesive films in relation to their permeability. One adhesive of each class was investigated: OptiBond FL; One-Step; Clearfil Protect Bond; and Xeno III. Adhesive films were prepared and cured with XL-2500 (3M ESPE) for 20, 40 or 60 s. Polymerization kinetic curves of the adhesives tested were obtained with differential scanning calorimetry (DSC) and data were correlated with microhardness. The permeability of the adhesives under the same experimental conditions was evaluated on human extracted teeth connected to a permeability device and analysed statistically. The results showed that the extent of polymerization obtained from DSC exotherms was directly correlated with microhardness. An increased level of polymerization after prolonged light-curing was confirmed for all adhesives. Simplified adhesives exhibited a lower extent of polymerization and showed incomplete polymerization, even after 60 s. An inverse correlation was found between the degree of cure and the permeability. This study supports the hypothesis that the permeability of simplified adhesives is correlated with incomplete polymerization of resin monomers and the extent of light exposure. These adhesives may be rendered less permeable by using longer curing times than those recommended by the respective manufacturer.

Adhesives↗
PubMed2000

The effect of sodium lauryl sulphate, triclosan and zinc on the permeability of normal oral mucosa.

OBJECTIVE: Sodium lauryl sulphate (SLS), an important component in many oral health products, is well established as a contact irritant in skin. Recent studies have suggested that it may also affect the structural integrity of oral mucosa. SLS is rarely used alone in dentifrices or mouthwashes and the aim of this study was to establish the effect of SLS both alone and in combination with Triclosan (TCN) and zinc (Zn) on the permeability barrier properties of normal human oral mucosa. METHOD: Ventral tongue mucosa was obtained from nine males and seven females within 60 h of death and stored frozen at -70 degrees C until use. The permeability of the tissue to tritiated water was measured after pretreatment for 15 min with SLS alone, SLS/TCN, SLS/Zn and a SLS/TCN/Zn mixture. Treatment with distilled water (DW) served as control. The histological appearance of the tissue before and after treatment was also examined by light microscopy. RESULTS: SLS treatment caused a significant increase in water permeability compared to control tissue (Kp = 11.7 +/- 1.00; 4.96 +/- 0.50 respectively; P < 0.005). Treatment with a SLS/TCN/Zn mixture, however, had no effect on the permeability to water (Kp = 5.5 +/- 0.56). Histological examination revealed that tissue exposed to SLS had a marked disruption of the epithelial surface whilst tissue treated with a SLS/TCN/Zn mixture was indistinguishable from controls. CONCLUSION: Although mucosa exposed to SLS alone showed an increase in permeability to water, the addition of TCN and Zn to SLS appeared to prevent this effect. As SLS is included in some dental products to solubilise compounds such as TCN, its presence may have no effect on the permeability barrier property of oral mucosa.

Adult↗
PubMed2005

In silico predictions of drug solubility and permeability: two rate-limiting barriers to oral drug absorption.

Aqueous drug solubility and intestinal drug permeability are two of the most important factors influencing drug absorption. If the developability of a drug is to be included in the lead optimization, new experimental and computational models of solubility and permeability are needed. These models must have the capacity to handle a large amount of data. Nowadays, epithelial cell culture models such as Caco-2 are routinely used to assess intestinal drug permeability and transport in drug discovery settings. The permeability values obtained from the Caco-2 cell monolayers have been traditionally used to devise in silico models for the prediction of drug absorption. In this paper, the use of molecular surface areas as descriptors of permeability and solubility will be reviewed. Moreover, a virtual filter for the prediction of oral drug developability based on the successful combination of in vitro and in silico models of drug permeability and aqueous drug solubility will be discussed.

Administration, Oral↗
PubMed1981

Specific permeability properties of demyelinated rat nerve fibres.

The specific permeability properties of isolated rat fibres with diphtheria toxin induced paranodal demyelination were investigated in potential clamp experiments. Nodal widening (4 to 6 micrometers) and paranodal demyelination (20 to 90 micrometers) were associated with a very large increase in the normally low delayed K-permeability (greater than 10 times). The resting K-permeability (which was comparatively large in the rat fibres) was similarly increased, which decreased action potential amplitude and excitability. Fibres with paranodal demyelination had, in addition, a large increase in the maximum peak Na-permeability (2 to 5 times the normal), which indicated that excitability was upheld by formation of new Na-permeability sites. The conduction defects in demyelinated fibres can therefore not be related to the size of the demyelination, but to the specific permeability changes in the demyelinated segment.

Action Potentials↗
PubMed1998

A permeability barrier in the dorsal wall of the equine hoof capsule.

The permeability barrier in the dorsal wall of the equine hoof capsule was studied by means of horseradish peroxidase (HRP) in 0.9 N saline solution as a water soluble tracer. Section were treated with 3'3'-diaminobenzidine tetrachloride (DAB) and before dissection the quality of the horn of feet from 10 horses was assessed and given a subjective grade as either good or poor. Blocks of tissue from each horse were left in either an oven at 60 degrees C or in water for 2 weeks before treatment in HRP, sectioning and DAB solution. Regions observed were i) outer surface, ii) outermost layers of the horn, iii) cut edge of the outer layer, iv) inner layer of horn, v) cut edge of the inner layer and vi) laminae. Horn deemed to be normal horn and of good 'quality' showed very slight penetration of HRP 3-5 cell layers deep in the outer layer. The cut edge of the outer layer of the wall of the 'normal' horn also showed minimal penetration of HRP through the intercellular spaces. The cut edge of the inner layers of the wall of normal, good quality horn showed penetration of the tracer up to 20 cell layers deep, with HRP in both the intercellular spaces and within the cells. In contrast, sections of horn from horses with brittle feet showed deep cracks in the outer surface into which the HRP had penetrated. Good quality horn showed no change in the position of the permeability barrier after soaking in water for 14 days, but the brittle horn showed an increase in permeability to HRP. In brittle horn, reaction product was seen deep within the section in the intercellular spaces of the intertubular horn only. Placing horn in an oven had no effect on the permeability barrier. The permeability barrier of the dorsal wall of the equine hoof capsule differs with the layer of the wall. Horn considered to be of poor quality had a weaker permeability barrier than horn of good quality.

Animals↗
PubMed1982

Permeability of canine submandibular glands to blood-borne horseradish peroxidase: effects of transient ductal obstruction during secretion.

Outflow obstruction of the submandibular duct, for a short period during parasympathetic secretion, caused an increase in glandular permeability to horseradish peroxidase. Higher frequencies of parasympathetic nerve stimulation during the obstructive period induced greater increases in the permeability. It is likely that the intraluminal distensions had disrupted some tight junctions and so permitted a greater paracellular leakiness. The damage tended to induce ballooning between striated ductal cells, similar to the appearances observed by Emmelin, Garrett & Gjörstrup (1977 a) when sympathetic secretion was accompanied by myoepithelial contraction against a raised outflow pressure. The present results have been compared with experimental data from other workers and give support to the idea that tight junctions can behave in a sieve-like manner towards the back-diffusion of molecules across them. This work indicates that there is a great need for care in permeability studies. It is possible that some permeability changes observed by other workers may have been the consequences of physical damage between cells. Our findings reinforce the need for morphological assessment of the glands after permeability experiments. In man it is likely that naturally occurring or artificially induced obstructive events may at times create similar permeability changes and these may enable protective substances to pass from the blood to the saliva. This affords possible explanation for such phenomena as the therapeutic value that often accrues from sialography and the efficacy of many different antibiotics in obstructive sialadenitis, despite the fact that most antibiotics do not normally permeate to the saliva.

Animals↗
PubMed1976

The passive permeability of the skin of anuran amphibia: a comparison of frogs (Rana pipiens) and toads (Bufo marinus).

1. Efflux of Na across dorsal skin, in vitro (bathed on both sides with Ringer solution), of frogs and toads were similar, but it was greater in ventral skin from the latter. 2. The efflux of Na declined, in both species, when the external surface of ventral, but not dorsal, skin was exposed to hyposmotic solutions with a low Na concentration. This change in Na permeability was influenced by the low osmotic concentration as well as the low Na concentration. 3. Efflux of Cl was similar in both the dorsal and ventral skin preparations (Ringer on both sides) from frogs and toads. 4. Chloride efflux declined in all skin preparations exposed on the external surface to dilute Ringer solution. Solute replacement with sucrose or choline or Na2SO4 showed that the decreased Cl efflux was principally due to the low Cl concentration, though Na may also contribute. This observation suggests the presence of Cl-/Cl- exchange diffusion mechanism. 5. Cutaneous urea permeability was less in toads than frogs and the dorsal and ventral skin was similar with respect to this solute in each species. 6. The presence of external hyposmotic solutions reduced the efflux, but not the influx, of urea across frog, but not toad, skin and it appeared that solvent 'drag' may contribute to this change. 7. Diffusion permeability to water was greater in frogs than toads and in the latter the ventral skin was more permeable than the dorsal. 8. The passive permeability of amphibian skin shows considerable interspecific and regional differences to various molecules which do not necessarily parallel each other. The control of passive cutaneous permeability appears to involve a variety of specific mechanisms, the distribution of which may have evolved during their adaptation to different environments.

Animals↗
PubMed1977

Human erythrocyte anion permeabilities measured under conditions of net charge transfer.

1. The permeability of the human erythrocyte to anions has been measured under conditions of net charge transfer: for Cl(-) and HCO(3) (-) ions, at 37 degrees C, this permeability is 5 orders of magnitude too small to account for the rate of the electroneutral anion exchange which is responsible for the chloride, or Hamburger, shift.2. The method is an indirect one in which the ionophore, valinomycin, is used to increase the erythrocyte K(+) permeability: in the absence of permeant cation externally, the rate of the resulting K(+) efflux may be limited by the slowness of the accompanying anion efflux, allowing the true anion permeability to be estimated.3. The average Cl(-) permeability estimated in ACD-stored erythrocytes (seven experiments) and erythrocytes from fresh blood (two experiments) was 2.1 x 10(-8) cm/sec at 37 degrees C and pH 7.4: this may also be expressed as a Cl(-) conductance of about 1.0 x 10(-5) Omega(-1) cm(-2). The apparent activation energy for net efflux of Cl(-) was found to be 3.9 kJ/mole (16.4 kcal/mole).4. In fresh cells, the ratios of Cl(-), HCO(3) (-), Br(-) and I(-) permeabilities (or conductances) were 1:0.8:1.5:5. The three halide ions follow Eisenman's Sequence I, representing a binding site of low field strength.

Anions↗
PubMed1992

Effect of colcemid on the water permeability response to vasopressin in isolated perfused rabbit collecting tubules.

1. The effect of the microtubule-disruptive agent, colcemid (N-deacetyl-N-methyl-colchicine), on the water permeability response to vasopressin has been investigated in isolated cortical collecting tubules from the rabbit kidney perfused in vitro. 2. Pretreatment of collecting tubules with colcemid inhibited the increase in water permeability elicited by vasopressin, 50 microU ml-1, in a time- and dose-dependent manner. After 75 min exposure to the drug, inhibition of the response to the hormone averaged 72 +/- 6% (n = 4, P < 0.01) at a colcemid concentration of 7.2 x 10(-5) M. Inhibition was estimated to be half-maximal at a colcemid concentration of 1.9 x 10(-6) M. 3. Colcemid, 2.7 x 10(-7) to 7.2 x 10(-5) M, had no effect on basal water permeability nor on the increase in lumen negative potential difference (PD) induced by the hormone. 4. Lumicolcemid, an isomer of colcemid that does not disrupt microtubules, had no influence on the water permeability response to vasopressin. 5. Pretreatment with colcemid, 2.7 x 10(-5) M, for 45 min inhibited the water permeability response to 8-CPT-cAMP, 1.8 x 10(-5) M, by 38 +/- 4% (n = 5, P < 0.01). 6. When collecting tubules were exposed to colcemid, 5.5 x 10(-5) M, for 45 min after the hydrosmotic response to vasopressin had been established, the drug had no influence on the maintenance of the raised water permeability. 7. The results provide further evidence that cytoplasmic microtubules play a role in the initiation of the hydrosmotic response to vasopressin in the mammalian collecting tubule at a site distal to the generation of cyclic AMP.

Animals↗
PubMed1995

Developmental changes in blood-brain barrier potassium permeability in the rat: relation to brain growth.

1. The potassium permeability of the blood-brain barrier (BBB) was determined in anaesthetized rats aged between 21 days gestation and adult using 86Rb+ as a marker for potassium. 2. The brain influx rate constant for 86Rb+ was high in fetal cortex at 21 days gestation (42.5 +/- 4.3 microliters g-1 min-1) but had decreased markedly by just after birth (12.2 +/- 0.6 microliters g-1 min-1). There was a further, gradual, postnatal decline to 7.0 +/- 0.3 microliters g-1 min-1 by 50 days after birth. 3. Developmental changes in passive BBB permeability were examined over the same age range using 14[C]urea. These studies showed similar developmental changes in influx rate to those found for 86Rb+. Specifically, a marked perinatal decline followed by a more gradual postnatal fall. Thus, the changes in potassium permeability probably reflect a decrease in the BBB paracellular leak during development. 4. The changes in BBB permeability coincide with changes in the rate of brain growth and the associated rate of brain potassium accumulation. As the potassium permeability properties of the adult BBB would provide insufficient potassium influx to meet the requirement associated with fetal brain growth, it is suggested that need for potassium may be the reason for the greater BBB permeability early in development.

Animals↗
PubMed2002

Effects of perfusion rate on permeability of frog and rat mesenteric microvessels to sodium fluorescein.

The permeability, P(S), to sodium fluorescein (Stokes-Einstein radius = 0.45 nm) has been measured in single mesenteric capillaries of pithed frogs and anaesthetised rats as perfusion velocity, U, was varied over a range from 400 up to 2000-10,000 microm s(-1). P(S) increased linearly with U. In 20 frog capillaries, mean (+/- S.E.M.) P(S) (in microm s(-1)) = 9.35 (+/- 1.55)U x 10(-5) + 0.244 (+/- 0.0291). Similarly, in nine rat venules, mean P(S) = 1.62 (+/- 0.385)U x 10(-4) + 0.375 (+/- 0.025). The flow-dependent component of permeability could be reversibly abolished in frog capillaries by superfusing with 100 microM noradrenaline and by superfusing rat venules with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (20 microM). It was shown that changes in microvascular pressure accompanying changes in U during free perfusion could account for only 15 % of the changes in P(S), i.e. 85 % of the changes in P(S) were changes in the permeability coefficient itself. A comparison between the changes in P(S) with U and the previously described changes in microvascular permeability to K(+) with U, suggest that if the flow-dependent component of permeability is modelled as a population of pores of constant size, these have radii of 0.8 nm. Such a pathway would limit flow-dependent permeability to small hydrophilic molecules and have minimal effect on net fluid exchange.

Animals↗
PubMed2005

Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+ concentration in the regulation of vascular permeability in Rana in vivo.

Vascular permeability is assumed to be regulated by the cytosolic Ca(2+) concentration ([Ca(2+)](c)) of the endothelial cells. When permeability is increased, however, the maximum [Ca(2+)](c) appears to occur after the maximum permeability increase, suggesting that Ca(2+)-dependent mechanisms other than the absolute Ca(2+) concentration may regulate permeability. Here we investigate whether the rate of increase of the [Ca(2+)](c) (d[Ca(2+)](c)/dt) may more closely approximate the time course of the permeability increase. Hydraulic conductivity (L(p)) and endothelial [Ca(2+)](c) were measured in single perfused frog mesenteric microvessels in vivo. The relationships between the time courses of the increased L(p), [Ca(2+)](c) and d[Ca(2+)](c)/dt were examined. L(p) peaked significantly earlier than [Ca(2+)](c) in all drug treatments examined (Ca(2+) store release, store-mediated Ca(2+) influx, and store-independent Ca(2+) influx). When L(p) was increased in a store-dependent manner the time taken for L(p) to peak (3.6 +/- 0.9 min during store release, 1.2 +/- 0.3 min during store-mediated Ca(2+) influx) was significantly less than the time taken for [Ca(2+)](c) to peak (9.2 +/- 2.8 min during store release, 2.1 +/- 0.7 min during store-mediated influx), but very similar to that for the peak d[Ca(2+)](c)/dt to occur (4.3 +/- 2.0 min during store release, 1.1 +/- 0.5 min during Ca(2+) influx). Additionally, when the increase was independent of intracellular Ca(2+) stores, L(p) (0.38 +/- 0.03 min) and d[Ca(2+)](c)/dt (0.30 +/- 0.1 min) both peaked significantly before the [Ca(2+)](c) (1.05 +/- 0.31 min). These data suggest that the regulation of vascular permeability by endothelial cell Ca(2+) may be regulated by the rate of change of the [Ca(2+)](c) rather than the global [Ca(2+)].

Animals↗
PubMed2002

Effect of fluid shear stress on the permeability of the arterial endothelium.

The localization of atherosclerotic lesions is due, in part, to regional variations in the permeability of arterial endothelium to macromolecules. In turn, endothelial permeability may be influenced by fluid shear stresses. The spatial variation in endothelial permeability is reviewed and evidence for shear stress dependence upon permeability is presented. These results are examined in light of various signaling mechanisms that increase permeability by increasing the transport of water and macromolecules through the junctions separating endothelial cells. Signaling pathways cause a change in the dense peripheral band of actin and actin stress fibers or alter the phosphorylation of junction proteins which affects their ability to localize in junctions. Future directions to clarify the effect of shear stress on permeability are considered.

Arteries↗
PubMed2004

Development of a computational approach to predict blood-brain barrier permeability.

The objectives of this study were to generate a data set of blood-brain barrier (BBB) permeability values for drug-like compounds and to develop a computational model to predict BBB permeability from structure. The BBB permeability, expressed as permeability-surface area product (PS, quantified as logPS), was determined for 28 structurally diverse drug-like compounds using the in situ rat brain perfusion technique. A linear model containing three descriptors, logD, van der Waals surface area of basic atoms, and polar surface area, was developed based on 23 compounds in our data set, where the penetration across the BBB was assumed to occur primarily by passive diffusion. The correlation coefficient (R(2)) and standard deviation (S.D.) of the model-predicted logPS against the observed are 0.74 and 0.50, respectively. If an outlier was removed from the training data set, the R(2) and S.D. were 0.80 and 0.44, respectively. This new model was tested in two literature data sets, resulting in an R(2) of 0.77 to 0.94 and a S.D. of 0.38 to 0.51. For comparison, four literature models, logP, logD, log(D. MW(-0.5)), and linear free energy relationship, were tested using the set of 23 compounds primarily crossing the BBB by passive diffusion, resulting in an R(2) of 0.33 to 0.61 and a S.D. of 0.59 to 0.76. In summary, we have generated the largest PS data set and developed a robust three-descriptor model that can quantitatively predict BBB permeability. This model may be used in a drug discovery setting to predict the BBB permeability of new chemical entities.

Algorithms↗