The landscape of drug resistant absence seizures in adolescents and adults: Pathophysiology, electroclinical spectrum and treatment options.

The persistence of typical absence seizures (AS) in adolescence and adulthood may reduce the quality of life of patients with genetic generalized epilepsies (GGEs). The prevalence of drug resistant AS is probably underestimated in this patient population, and treatment options are relatively scarce. Similarly, atypical absence seizures in developmental and epileptic encephalopathies (DEEs) may be unrecognized, and often persist into adulthood despite improvement of more severe seizures. These two seemingly distant conditions, represented by typical AS in GGE and atypical AS in DEE, share at least partially overlapping pathophysiological and genetic mechanisms, which may be the target of drug and neurostimulation therapies. In addition, some patients with drug-resistant typical AS may present electroclinical features that lie in between the two extremes represented by these generalized forms of epilepsy.

Sleep and epilepsy: A clinical and pathophysiological overview.

The interaction between sleep and epilepsy is complex. A better understanding of the mechanisms linking sleep and epilepsy appears increasingly important as it may improve diagnosis and therapeutic strategies in patients with epilepsy. In this narrative review, we aim to (i) provide an overview of the physiological and pathophysiological processes linking sleep and epilepsy; (ii) present common sleep disorders in patients with epilepsy; (iii) discuss how sleep and sleep disorders should be considered in new therapeutic approaches to epilepsy such as neurostimulation; and (iv) present the overall nocturnal manifestations and differential diagnosis between epileptic seizures and parasomnia.

Additive manufacturing of hierarchical injectable scaffolds for tissue engineering.

We present a 3D-printing technology allowing free-form fabrication of centimetre-scale injectable structures for minimally invasive delivery. They result from the combination of 3D printing onto a cryogenic substrate and optimisation of carboxymethylcellulose-based cryogel inks. The resulting highly porous and elastic cryogels are biocompatible, and allow for protection of cell viability during compression for injection. Implanted into the murine subcutaneous space, they are colonized with a loose fibrovascular tissue with minimal signs of inflammation and remain encapsulation-free at three months. Finally, we vary local pore size through control of the substrate temperature during cryogenic printing. This enables control over local cell seeding density in vitro and over vascularization density in cell-free scaffolds in vivo. In sum, we address the need for 3D-bioprinting of large, yet injectable and highly biocompatible scaffolds and show modulation of the local response through control over local pore size. STATEMENT OF SIGNIFICANCE: This work combines the power of 3D additive manufacturing with clinically advantageous minimally invasive delivery. We obtain porous, highly compressible and mechanically rugged structures by optimizing a cryogenic 3D printing process. Only a basic commercial 3D printer and elementary control over reaction rate and freezing are required. The porous hydrogels obtained are capable of withstanding delivery through capillaries up to 50 times smaller than their largest linear dimension, an as yet unprecedented compression ratio. Cells seeded onto the hydrogels are protected during compression. The hydrogel structures further exhibit excellent biocompatibility 3 months after subcutaneous injection into mice. We finally demonstrate that local modulation of pore size grants control over vascularization density in vivo. This provides proof-of-principle that meaningful biological information can be encoded during the 3D printing process, deploying its effect after minimally invasive implantation.

Slug/Pcad pathway controls epithelial cell dynamics in mammary gland and breast carcinoma.

Mammary gland morphogenesis results from the coordination of proliferation, cohort migration, apoptosis and stem/progenitor cell dynamics. We showed earlier that the transcription repressor Slug is involved in these functions during mammary tubulogenesis. Slug is expressed by a subpopulation of basal epithelial cells, co-expressed with P-cadherin (Pcad). Slug-knockout mammary glands showed excessive branching, similarly to Pcad-knockout. Here, we found that Slug unexpectedly binds and activates Pcad promoter through E-boxes, inducing Pcad expression. We determined that Pcad can mediate several functions of Slug: Pcad promoted clonal mammosphere growth, basal epithelial differentiation, cell-cell dissociation and cell migration, rescuing Slug depletion. Pcad also promoted cell migration in isolated cells, in association with Src activation, focal adhesion reorganization and cell polarization. Pcad, similarly to Slug, was required for in vitro 3D tubulogenesis. Therefore, Pcad appears to be responsible for epithelial-mesenchymal transition-linked plasticity in mammary epithelial cells. In addition, we found that genes from the Slug/Pcad pathway components were co-expressed and specifically correlated in human breast carcinomas subtypes, carrying pathophysiological significance.

Intravenous Levetiracetam as first-line treatment of status epilepticus in the elderly.

BACKGROUND: Status epilepticus is a condition of prolonged/repetitive seizures that often occurs in the elderly. Treatment in the elderly can be complicated by serious side effects associated with traditional drugs. OBJECTIVE: The aim of this pilot study was to evaluate the short-term efficacy/safety of intravenously administered LEV (IVLEV) as the treatment of choice for SE in the elderly. METHODS: We enrolled nine elderly patients (five female/four male; median age 78 years) with SE. Two patients had a previous diagnosis of epilepsy; in the remaining seven, SE was symptomatic. SE was convulsive in five and non-convulsive in four. All the patients presented concomitant medical conditions (arrhythmias/respiratory distress/hepatic diseases). As the traditional therapy for SE was considered unsafe, IVLEV was used as first-line therapy (loading dose of 1500 mg/100 ml/15 min, mean maintenance daily dose of 2500 mg/24 h) administered during video-EEG monitoring. RESULTS/CONCLUSIONS: In all the patients but one, IVLEV was effective in the treatment of SE and determined either the disappearance of (7/8), or significant reduction in (1/8), epileptic activity; no patient relapsed in the subsequent 24 h. No adverse events or changes in the ECG/laboratory parameters were observed. These data suggest that IVLEV may be an effective/safe treatment for SE in the elderly.

Molecularly imprinted polymers for the recognition of proteins: the state of the art.

Molecular imprinting has proved to be an effective technique for the creation of recognition sites on a polymer scaffold. Protein imprinting has been a focus for many chemists working in the area of molecular recognition, since the creation of synthetic polymers that can specifically recognise proteins is a very challenging but potentially extremely rewarding objective. It is expected that molecularly imprinted polymers (MIPs) with specificity for proteins will find application in medicine, diagnostics, proteomics, environmental analysis, sensors and drug delivery. In this review, the authors provide an overview of the progress achieved in the decade between 1994 and 2005, with respect to the challenging area of MIPs for protein recognition. The discussion furnishes a comparative analysis of different approaches developed, underlining their relative advantages and disadvantages and highlighting trends and possible future directions.

Improvement of norfloxacin oral bioavailability by EDTA and sodium caprate.

The EDTA and sodium caprate (Na caprate) effects on the oral bioavailability of norfloxacin were tested. It was found that absorption kinetic of norfloxacin was markedly accelerated when mixed with EDTA or Na caprate in a ratio of 1:1. When mixed with the absorption enhancers in a ratio of 1:5, only Na caprate improved norfloxacin bioavailability significantly. In vitro dissolution tests demonstrated that EDTA and Na caprate increased norfloxacin dissolution kinetic. However, the correlation between bioavailability and in vitro dissolution improvement was not clearly established. So, we can conclude that the solubilizing property of EDTA and Na caprate did not take a prominent part in norfloxacin absorption.

[Priapism: decisional algorithm, our experience, and role of sildenafil in sexual rehabilitation]. / Priapismo: algoritmo decisionale, nostra esperienza e ruolo del sildenafil nella riabilitazione sessuale.

OBJECTIVE: We report our experience in the management of priapism. MATERIALS AND METHODS: In a 2-year period we observed 7 patients of whom 4 presented with low flow and 3 with high flow priapism. RESULTS: In 2 of the patients with ischemic priapism, simple blood aspiration from the corpora allowed for a quick detumescence, while in the other 2 cases a derivative intervention (1 spongio cavernous and 1 glans cavernous) had to be performed. In all the 3 patients with high flow priapism we performed a superselective arteriography that obtained the visualisation of the arteriovenous fistula. These patients restarted their sexual activity after about three months. At six months a patient with low flow priapism restored sexual activity due to sildenafil 50 mg. CONCLUSION: The importance of distinguishing low and high flow priapism was confirmed.

[Abdomino-scrotal hydrocele]. / L'idrocele inguino-funicolo-vaginale.

In this paper two cases of abdomino-scrotal hydrocele are described. One of these cases resulted really singular due to its rare dimensions as well as to its secondary renal obstruction. After a careful description of the cases a detailed review of the literature as well as of the etiopathogenetic theories of this rare pathology are reported.

Hyperbaric oxygen therapy in the treatment of Fournier's disease in 11 male patients.

PURPOSE: Optimal tissue oxygenation, as obtained by hyperbaric oxygen therapy, potentiates or restores the host's bactericidal mechanisms and wound healing activity in patients afflicted by serious synergeic aerobic and anaerobic infections of the cutaneous and subcutaneous tissues. Furthermore, hyperbaric oxygen therapy has a direct toxic effect on anaerobic bacteria. We describe our experience with hyperbaric oxygen therapy in the treatment of 11 patients with Fournier's syndrome. MATERIALS AND METHODS: The average age of our patients was 59.5 years; the most common predisponsing condition was diabetes. All patients were treated with antibiotic therapy and hyperbaric oxygen therapy (minimum 5 and maximum 24 cycles, consisting of 90 minutes 2.5 atmosphere absolute pressure). Furthermore, 6 of these patients underwent surgical débridement of the wounds and 3 patients underwent delayed reconstructive surgery. RESULTS: The results we obtained with hyperbaric oxygen therapy as an adjunctive measure for the treatment of these infections were excellent; our mortality rate for Fournier's disease was 0. Moreover, no complications whatsoever were observed. Furthermore, the 3 patients who underwent delayed corrective surgery presented with well healed tissues and their operations were not complicated by infections or other pathological conditions. CONCLUSIONS: We believe that our findings, although limited in number, underline the excellent results that can be obtained with hyperbaric oxygen therapy as an adjunct treatment in Fournier's disease.

Influence of poly(DL-lactide) nanocapsules on the biliary clearance and enterohepatic circulation of indomethacin in the rabbit.

Following intravenous administration, the uptake of colloidal drug carriers by cells of the mononuclear phagocyte system, mainly the Kuppfer cells, may concentrate an encapsulated drug close to the liver parenchymal cells and facilitate its biliary excretion and enterohepatic circulation. To test this hypothesis indomethacin was administered (10 mg/kg) in four groups of 10 rabbits each by intravenous infusion at a constant rate over 2 hr, either in its free form (aqueous solution) or as nanocapsules prepared from preformed poly(DL-lactide). Unchanged drug was assayed in plasma of the two control (sham-operated) groups and in both plasma and bile of the two bile-cannulated groups. Pharmacokinetic analysis led to the conclusion that the uptake of nanocapsules by liver macrophages reduces the concentration of the drug by enhancing its total clearance. This enhancement was due to an increase in biliary clearance, as a result of parallel increases in bile concentration and biliary excretion of the drug. It was also demonstrated that nanocapsules enhance the enterohepatic circulation of indomethacin.

[The effect of dilutions of Apis mellifica and Apium virus on ultraviolet light-induced erythema in the guinea pig]. / Mise en évidence des effets de dilutions d'Apis mellifica et d'Apium virus vis-à-vis de l'érythème provoqué par un rayonnement UV chez le cobaye.

Dilutions of Apis mellifica (obtained from the whole bee) and Apium virus (obtained from bee venom) are used classically in homeopathy for inflammatory symptoms with edema, erythema and pruritus (Lewis triad). Using a method examining the evolution of UV induced erythema in the guinea pig, the authors show the following dilutions of Apis mellifica 7 CH(10(-14)), 9 CH(10(-18)) and of Apium virus 5 CH(10(-10)), 7 CH(10(-14)), 9 CH(10(-18)) exert an action on experimental erythema. The results are statistically significant for the dilutions at the 48th hour after irradiation.

In vivo neutralization of low-molecular weight heparin fraction CY 216 by protamine.

The neutralization in vivo of a low molecular weight heparin by protamine was investigated. Large doses and excessive doses of intravenously administered CY 216 were studied. An intravenous injection of protamine given 10 minutes after the administration of CY 216 did not cause the studied biologic parameters to return to normal levels, but merely attenuated them, whatever the protamine dosage tested. In contrast, the bleeding time and the volume of blood loss resumed normal values that were close to those observed in the controls. This dissociation of actions cannot be explained at present. The ratio of protamine to CY 216 dosage that produced the best results was 1 antiheparin U of protamine to 2 anti-Xa U of CY 216. Nevertheless CY 216 appeared to have a small hemorrhagic potential.

Activite succino-deshydrogenasique des microsomes et mode d'incorporation du succinate 2,3-(14)C dans les acides gras des microsomes de foie de rat in vitro.

The incorporations of 2,3-(14)C-succinate 2-(14)C-acetate into fatty acids of different cellular fractions of rat liver were studied. Acetate was incorporated mainly into supernatant and succinate into microsomal fatty acids. Mitochondria only could intensively decarboxylate pyruvate. Avidine inhibited fatty acid synthesis from succinate mainly in the supernatant. It is suggested that succinate is an important physiological precursor of fatty acids in the liver and that an active succino-dehydrogenase is present in microsomes.

Action de l'insuline sur la synthese des acides gras dans les differentes fractions cellulaires de tissu adipeux blanc de rat in vivo.

The synthesis of fatty acids in mitochondria, microsomes and supernatant of rat adipose tissue was studied after administration of U-(14)C(-) glucose. The major site of fatty acids synthesis was the supernatant in controls and the microsomes in insulin-treated animals. The action of insulin cannot be explained only by an increase of the intra-cellular penetration of glucose. An action on enzyme synthesis is probable.