Modeling birds on wires.

In this paper we introduce a mathematical model to study the group dynamics of birds resting on wires. The model is agent-based and postulates attraction-repulsion forces between the interacting birds: the interactions are "topological", in the sense that they involve a given number of neighbors irrespective of their distance. The model is first mathematically analyzed and then simulated to study its main properties: we observe that the model predicts birds to be more widely spaced near the borders of each group. We compare the results from the model with experimental data, derived from the analysis of pictures of pigeons and starlings taken in New Jersey: two different image elaboration protocols allow us to establish a good agreement with the model and to quantify its main parameters. We also discuss the potential handedness of the birds, by analyzing the group organization features and the group dynamics at the arrival of new birds. Finally, we propose a more refined mathematical model that describes landing and departing birds by suitable stochastic processes.

Eudragit E100 as a drug carrier: the remarkable affinity of phosphate ester for dimethylamine.

Therapeutic agents containing phosphate groups in their molecules have increasing therapeutic impact. The object of this study was to characterize the cationic polyelectrolyte Eudragit E100 (EuE100) as a carrier for drugs containing phosphate groups, using dexamethasone phosphate (DP) as a model. A series of EuE100-DP complexes was obtained by acid-base reaction in which DP neutralized 12.5-75% of the basic groups of EuE100. The solids obtained after solvent evaporation revealed by spectroscopic characterization the complete reaction between the components through the ionic interaction between the amine groups of EuE100 and the phosphate groups of DP. The reversibility of the counterion condensation, evaluated through the proton-withdrawing effect produced by the ionic exchange generated by titration with NaCl, showed a remarkable high affinity between EuE100 and DP. In line, drug delivery in bicompartimental Franz cells toward water as receptor medium was very slow (2% in 6 h). However, it was increased as water was replaced by NaCl solution, which upon diffusion generates ionic exchange. A sustained release of DP with noticeable zero order kinetics accounted for a remarkable high affinity, mainly due to the electrostatic attraction. The release rate remains constant regardless of the saline concentration of the media. Besides, the delivery control is maintained even in gastric simulated fluid, a property not informed previously for EuE100 complexes.

Multinuclear solid state NMR investigation of two polymorphic forms of ciprofloxacin-saccharinate.

Two polymorphic forms of a novel pharmaceutical compound, ciprofloxacin-saccharinate (CIP-SAC), are analyzed using one dimensional (1D) and two dimensional (2D) (1)H nuclear magnetic resonance (NMR) at fast magic angle spinning (MAS). Additionally (15)N spectroscopy and (1)H-(13)C correlation experiments were performed to complement our conclusions. The 1D (1)H NMR spectra of CIP and complexes reveal valuable information about the ionic bonding between ciprofloxacin and saccharine. Additionally, these spectra allow us to perform a clear characterization of each solid form, giving the number of molecules per unit cell in one of the polymorphs. From 2D (1)H-(1)H spectra obtained through double quantum correlations we can arrive at important conclusions about the hydrogen bonding, conformation, and intra and inter-molecular interactions present in these compounds. Comparing and contrasting the (1)H-(1)H correlation data obtained for both polymorphic forms and taking into account the single crystal structure data existing for the solid form CIP-SAC (II) was possible to extract some conclusions on the polymorph CIP-SAC (I) where no single crystal information is available. (1)H MAS NMR is shown to be an important tool in the field of polymorphism and for the characterization of multicomponent pharmaceutical compounds.

Optimization versus randomness for car traffic regulation.

We focus on the differences among the analytical optimization of traffic flow on a road network, modeled by a fluid-dynamic approach, and a dynamic random one. In particular, two real urban networks are analyzed: Re di Roma Square, in Rome, and Via Parmenide crossing, in Salerno. With such two examples, it is possible to show that dynamic random algorithms are not the right choice for the improvement of traffic conditions.

Translational Research: A Future Strategy for Managing Squamous Cell Carcinoma of the Head and Neck?

BACKGROUND: Squamous Cell Carcinoma of the Head and Neck (SCCHN) are neoplasms arising from the epithelium of the first aero-digestive tract. They are very heterogeneous both clinically and biologically. Classic and well acknowledged risk factors are alcohol and tobacco consumption and other forms of smokeless tobacco assumption, although lately the incidence of Human Papilloma Virus (HPV)-related SCCHN is rapidly increasing. HPV-related tumors are very different from their alcohol and tobacco-associated counterpart, as they show strong chemo and radio sensitivity and thus can often be treated with conservative treatment strategies. Moreover, peculiar biologic features characterize HPV-related tumors, such as wild type TP53, low expression of Epidermal Growth Factor Receptor (EGFR), wild type CCND1 and high expression of P16. In contrast, alcohol and tobacco related SCCHN show opposite features, together with higher number of chromosomal and genetic abnormalities, conferring them chemo and radio resistance. METHODS: We have performed a narrative review of the PubMed database with the aim to study the mutational landscape of SCCHN. RESULTS: Several lines of evidence support the existence of at least two genetically different types of SCCHN, one virus-related and the other alcohol and/or tobacco-related, characterized by both clinical and biological opposite features. Virus related SCCHN are very chemo and radiosensitive, so suitable for organ preserving strategy, which in the near future may be induction chemotherapy followed by association of chemotherapy and underpowered radiotherapy. Alcohol and tobacco related SCCHN are themselves strongly heterogeneous and can be divided in different entities on the basis of the "Driver" genetic aberration, responsible for carcinogenesis. The most frequently mutated genes in alcohol and tobacco-related SCCHN are TP53, NOTCH1, CCND1, CDKN2A, EGFR and PI3KCA. CONCLUSIONS: Virus-related SCCHN can be managed with chemo-radiotherapy. Alcohol and tobacco-related tumors should be further characterized on the basis of their "Driver Mutations" in order to select effective targeted therapies.

Urinary excretion of ciprofloxacin after administration of extended release tablets in healthy volunteers. Swellable drug-polyelectrolyte matrix versus bilayer tablets.

This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, tmax, area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.

Design of novel antifungal mucoadhesive films. Part II. Formulation and in vitro biopharmaceutical evaluation.

This paper deals with the formulation of the mucoadhesive films containing nystatin. The design and formulation of the films were based on the mucoadhesive properties of carbomer 934P (CB) and carboxymethycellulose (NaCMC), and also on the plasticizer properties of polyethyleneglycol 400 (PEG400). A surfactant (ascorbyl palmitate, ASC16) was added to the system to aid in nystatin dispersion. Addition of these last two components produced a significant improvement in physical-mechanical properties (flexibility and strength) as well as an increase in the nystatin release rate. X-ray powder diffraction (XRPD) and scanning electronic microscopy (SEM) were used to evaluate the morphological changes in the films while PEG400 and ASC16 were added to the formulations. Furthermore, the in vitro nystatin profile release was determined.

Design of novel antifungal mucoadhesive films Part I. Pre-formulation studies.

In this work, pre-formulation studies concerning the design of novel mucoadhesive films have been carried out. The rationality of the design is based on the utilization of mucoadhesive polymers (carbomer and carboxymethylcellulose), a plasticizer (polyethyleneglycol 400, PEG400) and a surfactant (ascorbyl palmitate, ASC16). In the gel preparation, the casting method using water as a solvent was employed. To provide a better understanding of the structural arrangements produced during the casting process, the changes in morphology (Cryo-TEM) and rheology (viscosity) of the film forming gel were evaluated. When PEG400 was included as a plasticizer, a disorder was produced in the network, reflected in the globular structure adopted by the gel and the consequent decrease in viscosity. The addition of ASC16 improved the solubilization of nystatin and provoked a decrease in gel viscosity. However, as water was removed during casting, ASC16 produced a significant increase in the viscosity at the point in which the polymer concentrations were sufficient to strengthen the inter-polymeric interactions, giving rise to a more rigid tri-dimensional network.

Effect of ascorbic acid based amphiphiles on human erythrocytes membrane.

6-O-alkyl ascorbic acid esters (ASCn) are amphiphilic molecules that behave as surfactants in aqueous solution. These compounds show physico-chemical and aggregation properties that depend on the alkyl chain length, pH and temperature. It must consider that ASCn have shown some physical and rheological properties that suggest a potential utility as drug carriers. The present paper aims to evaluate the effects of these surfactants on human erythrocyte membranes. The membrane properties studied were: osmotic resistance in hypotonic media, shape transformation, and vesicle release at lytic concentration. According to our results, all properties depended on the length of the hydrophobic chain and they did not evolve monotonically. Finally, the study of ASCn interaction with erythrocyte membrane allowed us to postulate the crucial influence that the molecular structure exerts upon the manner in which amphiphiles interact with biological membranes and the effects involved in them.

The role of hyaluronan as a drug carrier to enhance the bioavailability of extended release ophthalmic formulations. Hyaluronan-timolol ionic complexes as a model case.

The aim of this work was to obtain information concerning the properties of ophthalmic formulations based on hyaluronic-drug ionic complexes, to identify the factors that determine the onset, intensity and duration of the pharmacotherapeutic effect. Dispersions of a complex of 0.5% w/v of sodium hyaluronate (HyNa) loaded with 0.5% w/v of timolol maleate (TM) were obtained and presented a counterionic condensation higher than 75%. For comparison a similar complex obtained with hyaluronic acid (HyH) was also prepared. Although the viscosity of HyNa-TM was significantly higher than that of HyH-TM, in vitro release of TM from both complexes showed a similar extended drug release profile (20-31% over 5h) controlled by diffusion and ionic exchange. Ocular pharmacokinetic study performed in normotensive rabbits showed that HyNa-TM complex exhibited attractive bioavailability properties in the aqueous humor (AUC and Cmax significantly higher and later Tmax) compared to commercial TM eye-drops. Moreover, a more prolonged period of lowered intra-ocular pressure (10h) and a more intense hypotensive activity was observed after instillation of a drop of HyNa-TM as compared to the eye-drops. Such behavior was related to the longer pre-corneal residence times (400%) observed with HyNa-TM complex. No significant changes in rabbit transcorneal permeation were detected upon complexation. These results demonstrate that the ability of HyNa to modulate TM release, together with its mucoadhesiveness related to the viscosity, affected both the pharmacokinetic and pharmacodynamic parameters. The HyNa-TM complex is a potentially useful carrier for ocular drug delivery, which could improve the TM efficacy and reduce the frequency of administration to improve patient compliance.

Biowaiver monographs for immediate release solid oral dosage forms: amitriptyline hydrochloride.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing amitriptyline hydrochloride are reviewed. Its therapeutic uses, its pharmacokinetic properties, the possibility of excipient interactions and reported BE/bioavailability (BA) problems are also taken into consideration. Literature data indicates that amitriptyline hydrochloride is a highly permeable active pharmaceutical ingredient (API). Data on the solubility according to the current Biopharmaceutics Classification System (BCS) were not fully available and consequently amitriptyline hydrochloride could not be definitively assigned to either BCS Class I or BCS Class II. But all evidence taken together, a biowaiver can currently be recommended provided that IR tablets are formulated with excipients used in existing approved products and that the dissolution meets the criteria defined in the Guidances.

Conception rates and serum progesterone concentration in dairy cattle administered gonadotropin releasing hormone 5 days after artificial insemination.

The objectives of this study were to determine the effect of administration of exogenous GnRH 5days after artificial insemination (AI) on ovarian structures, serum progesterone concentration, and conception rates in lactating dairy cows. In experiment 1, 23 Holstein cows were synchronized using the Ovsynch protocol. Five days after AI (day 0) cows were assigned randomly to receive either saline (saline; n=11) or 100microg GnRH (GnRH; n=12). To examine ovarian structures, ultrasonography was performed on day 1 and every other day beginning on day 5 until day 13. On days 5 and 13 blood samples were obtained to measure serum progesterone concentrations. All cows in the GnRH-treated group developed an accessory corpus luteum (CL), whereas cows in the saline group did not. Mean serum progesterone concentrations did not differ between GnRH and saline groups on day 5 (1.64+/-0.46ng/ml versus 2.04+/-0.48ng/ml). On day 13 serum progesterone concentrations were greater (P<0.05) in the GnRH group compared with saline (5.22+/-0.46ng/ml versus 3.36+/-0.48ng/ml). In experiment 2, 542 lactating cows, at two different commercial dairies, were used to test the effect of administering GnRH 5 days after AI on conception rates. Cows were synchronized and detected for estrus according to tail chalk removal. Cows detected in estrus received AI within 1h after detection of estrus. Five days after AI, cows were assigned randomly to receive either GnRH (n=266) or saline (n=276). Pregnancy status was determined by palpation per rectum of uterine contents approximately 40 days after AI. There was no effect of farm on conception rate. There was no effect of treatment as conception rates did not differ between GnRH and saline groups (26.7% GnRH versus 24.3% saline). Regardless of treatment, days in milk, parity, milk yield, and number of services had no effect on the odds ratio of pregnancy. In summary, the results of this study indicated that GnRH administered 5 days after AI increased serum progesterone by developing an accessory CL but did not improve conception rates in dairy cattle.

Time and incidence of ovulation and conception rates after incorporating estradiol cypionate into a timed artificial insemination protocol.

Two experiments were conducted to determine the effect of estradiol cypionate (ECP), when incorporated into a conventional GnRH-PGF(2alpha)-GnRH timed artificial insemination protocol (Ovsynch), on systemic estradiol (E(2)), time and incidence of ovulation, luteal development, and conception rate in Holstein cows. Our objective was to determine if administration of 0.25 mg of ECP at the time of the second GnRH injection would effectively synchronize ovulation and increase conception rate. In Experiment 1, lactating Holstein cows (n = 23; 58.7 +/- 1.2 d in milk) were synchronized with PGF(2alpha) (at d -10). Ten days later, Ovsynch was initiated with the administration of 100 mug of GnRH (d 0) followed by PGF(2alpha) on d 7. On d 9, cows were assigned randomly to be treated with either GnRH + 0.25 mg of ECP (OVS-ECP; n = 11) or GnRH and 1 mL of cottonseed oil (OVS-C; n = 12). Ovarian activity was monitored by ultrasonography on d 0, 7, and 9. To determine the time of ovulation, ultrasound examinations were conducted at 12 and 20 h posttreatment and then at least every 3 h until either 36 h posttreatment or ovulation was observed. Blood samples were collected on d 0, 7, 9, and 16 for progesterone analysis. Blood samples also were collected at the time of treatment (d 9, 0 h) and at 6, 12, 20, and 28 h for E(2) analysis. Incidence of ovulation did not differ between treatments. Mean ovulation time relative to the second GnRH administration was similar between treatments. Serum progesterone concentration did not differ between treatments at any time. Serum E(2) concentration was not different at the time of treatment (0 h); however, mean E(2) concentration was greater for the OVS-ECP group at 6 and 12 h after treatment compared with OVS-C. In Experiment 2, lactating dairy cows (n = 333) in 3 commercial herds were randomly assigned to OVS-ECP (n = 169) or OVS-C (n = 164). Cows were inseminated 22 to 24 h posttreatment. Conception rates did not differ between treatments. Estradiol cypionate treatment was successful in increasing serum E(2) when administered at the time of the second dose of GnRH in the Ovsynch protocol. Conception rates, however, were not affected by treatment.

Reduced food interaction and enhanced gastrointestinal tolerability of a new system based on risedronate complexed with Eudragit E100: Mechanistic approaches from in vitro and in vivo studies.

Novel complexes consisting of Eudragit E100-risedronate are presented. The oral bioavailability of risedronate in rats was determined through its percentage excreted in urine after administration of complexed or free risedronate in fed and fasted conditions. The evaluation of the risedronate gastro-duodenal irritation potential was carried out by macroscopic and histological analyses in an experimental rat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessed by dialysis with, mechanistic information about the interaction with calcium and the release of risedronate from the complexes being obtained using physiological solution and simulated gastric fluid without pepsin. Non-significant differences were observed in the urinary excretion of risedronate when the complex or free risedronate was administered to fasted rats. However, the urinary excretion of risedronate in the complex group was 4-times higher than in the free risedronate group when animals were concomitantly administered with food. This behavior was related to the high degree of counterionic condensation in the complex (86.5%), which led to a reduction in the calcium induced rate and magnitude of risedronate precipitation and resulted in a decrease in the gastroduodenal damage from the complex, as evidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate from the complex was observed toward water, simulated gastric fluid or physiological solution, through an ionic-exchange mechanism. In conclusion, complexation with Eudragit E100 could be a useful strategy to overcome the unfavorable properties of risedronate.

Benzenesulfonamide analogs of fluoroquinolones. Antibacterial activity and QSAR studies.

The structure-activity relationships (SAR) of new antibacterial benzenesulfonamidefluoroquinolones (BSFQs), coming from derivatization of N4-piperazinyl of ciprofloxacin (CIP) were studied. The behavior of the new BSFQ series was similar to the previously norfloxacin (NOR) analogs reported, making possible a quantitative structure-activity relationships (QSAR) analysis of the complete set of BSFQs. The presence of the benzenesulfonylamido (BS) groups shifted the activity of classic antimicrobial fluoroquinolones from being more active against Gram-negative to Gram-positive strains. QSAR studies through Hansch analysis showed a linear correlation of the activity with electronic and steric parameters. Small electron-donor groups would increase the in vitro activity against Gram-positive bacteria. Hydrophobic properties played a minor role when activity is measured as minimum inhibitory concentration (MIC). QSAR analysis also reinforces previous biological findings about the presence of new interactions with target topoisomerases.

The potential role of thrombolytic therapy in venous thrombosis.

BACKGROUND: Anticoagulant therapy for lower extremity deep-vein thrombosis (DVT) has been shown to reduce mortality from pulmonary embolism, but subsequent morbidity from the postthrombotic syndrome remains high. Thrombolytic therapy produces higher lysis rates of venous thrombi than heparin alone. Some studies suggest a lower incidence of postthrombotic sequelae after early use of streptokinase. These potential benefits are limited to those patients without contraindications for this therapy. METHODS: For the past 3 years we have prospectively studied patients with DVT documented by duplex scanning. The records of these patients were reviewed to determine what proportion of this population would have been candidates for thrombolytic therapy. For this analysis, contraindications to the use of thrombolytic agents included: (1) recent surgery (less than 1 month); (2) recent major trauma; (3) active or recent bleeding; (4) brain disease (cerebrovascular accident, brain tumor, arteriovenous malformation); (5) pregnancy; and (6) bleeding diathesis. Also, patients with prior ipsilateral DVT and those with acute symptoms present for 7 or more days were not considered to be candidates for thrombolytic therapy. RESULTS: A contraindication to thrombolytic therapy was present in 194 (93%) of 209 patients with a diagnosis of DVT, including four patients with a relative contraindication. Two or more contraindications were present in 65 cases (31%). Recent surgery was the most frequent factor precluding therapy, being present in 71 patients. A history of DVT in the affected leg was present in 45 patients. CONCLUSIONS: Only 15 (7%) of 209 patients with DVT exhibited no contraindications for thrombolytic treatment. Only a small fraction of patients with venous thrombosis will be potential candidates for this therapy.

Short communication: Conception rates following detection of estrus and timed AI in dairy cows synchronized using GnRH and PGF2alpha.

The objective of this study was to compare conception rates of cows exhibiting spontaneous estrus and receiving artificial insemination (AI) before completion of a timed AI protocol with cows that did not display estrus spontaneously, but were inseminated after 1 of 3 GnRH-PGF2alpha protocols. Cows (n = 432) in 2 herds were administered GnRH on d -7 and were tail-chalked daily. Cows detected in estrus before d 0 were inseminated immediately. Cows not detected in estrus by d 0 were administered PGF2alpha and were tail-chalked daily until 48 h after PGF2alpha. Cows detected in estrus from d -7 to 48 h after PGF2alpha were inseminated and designated as treatment A (n = 46). Cows not detected in estrus and not inseminated by 48 h after PGF2alpha were assigned randomly to receive either GnRH 48 h after PGF2alpha and timed AI 16 h later (treatment B; n = 132), or GnRH and timed AI 64 h after PGF2alpha (treatment C; n = 127), or timed AI 64 h after PGF2alpha (treatment D; n = 127). Pregnancy was diagnosed 38 to 45 d after AI by palpation per rectum of uterine contents. Nearly 11% of all cattle exhibited spontaneous estrus and received immediate AI. Herd did not influence the percentage of cows detected in estrus and inseminated. Conception rates did not differ among treatments. Conception rates differed between herds, but no interaction of herd x treatment was detected. No differences were detected between herds for days in milk, milk production, AI service number, or parity.

Venous diameter and compliance after deep venous thrombosis.

Duplex sonography was used to measure diameters of the common femoral, superficial femoral, and popliteal veins in 56 patients followed for more than 6 months after DVT and in 17 normal subjects. Diameter changes with Valsalva's maneuver were also measured as an index of venous compliance. Among patients with unilateral thrombosis, segments with residual disease were 0.07 to 0.28 cm smaller than the contralateral disease-free side (p < 0.05 for CFV and SFV) with a diameter index (ipsilateral/contralateral diameter) significantly less than that of normal subjects. In contrast, completely recanalized segments were not significantly different from the contralateral side and had diameter indices indistinguishable from normal subjects. Distensibility with Valsalva's maneuver was not significantly different from normal in DVT patients with either resolved or residual disease. Venous diameter does decrease following DVT, but returns to normal following complete recanalization and is not associated with chronic venous compliance changes.

The relationship of venous diameter to reflux, cephalad thrombus and cephalad reflux following deep venous thrombosis.

Duplex ultrasonography was used to measure the diameters of the common femoral, superficial femoral and popliteal vein segments in 123 patients following DVT. A cross sectional analysis was done based on the most recent visit to determine chronic venous diameter changes following DVT. Venous diameters in recanalized segments were smaller at all levels compared to those never occluded (p = 0.06 for CFV and p < 0.05 for SFV and PV). After accounting for a previous history of occlusion, the diameters of the segments with and without reflux were not significantly different. There was also no evidence of venodilation in segments caudal to cephalad reflux or thrombus. Recanalized veins are smaller in diameter than those which were never thrombosed. Cephalad thrombus or reflux is not associated with venodilatation of caudal segments. Reflux following DVT is probably secondary to valvular damage rather than hypertension, since there was no diameter difference between refluxing and non-refluxing segments.

Direct in vivo observation of transventricular absorption in the hydrocephalic dog using magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A model of chronic noncommunicating hydrocephalus in canines was developed, and gadolinium-DTPA (Gd-DTPA)-enhanced magnetic resonance imaging, physiologic and morphologic studies were performed to investigate transventricular absorption of cerebrospinal fluid. METHODS: Chronic hydrocephalus was induced in 12 mongrel dogs by injection of a silastic mixture into the prepontine cisterns. Ventricular pressure was measured during the development of hydrocephalus, and lateral ventriculo-ventricular perfusions with Gd-DTPA were performed under controlled conditions during serial magnetic resonance imaging studies. RESULTS: Hydrocephalus developed over an average of 129 +/- 24 days after induction, and the intraventricular pressure increased from an initial level of 14 +/- 4 cm H2O to a stabilized plateau of 25 +/- 5 cm H2O. Increased signal intensity in the brain matter, as seen on magnetic resonance images of chronic hydrocephalic dogs perfused with Gd-DTPA in the lateral ventricles, was consistent with the presence of the contrast agent in the periventricular extracellular space. This increased signal intensity was not observed in control animals. CONCLUSIONS: These results provide direct evidence of transventricular absorption in chronic hydrocephalus.