Microneedle-Assisted Delivery of Anti-Migraine Drugs Across Porcine Skin: Almotriptan Malate and Naratriptan Hydrochloride

Migraine is a common neurological disorder characterized by nausea, vomiting, photophobia, aching, fever, pain and chills. Triptans are selective serotonin agonists which can used to relieve migraine symptoms. Almotriptan malate and naratriptan hydrochloride are currently used for the management of migraine in the form of oral tablets. Oral tablets may be problematic for patients experiencing nausea and vomiting which are often associated with migraine. The microneedle-assisted transdermal drug delivery of these triptans may improve patient compliance. A vertical six-celled, static Franz diffusion cell system was used to conduct in vitro permeation experiments on porcine ear skin to determine the influence of microneedle-assisted transdermal delivery of both almotriptan malate and naratriptan hydrochloride. HPLC-MS analysis was performed using an Agilent 1200 series high performance liquid chromatography system in combination with an Agilent time of flight mass spectrometer (TOF-MS) system model 6230 (Agilent, Santa Clara, CA, USA). A reversed phase liquid chromatography column (Agilent Zorbax Eclipse Plus C18, 100 mm X 2.1 mm, 3.5 µm), was utilized for chromatographic separation. Confocal laser scanning microscopy was used to characterize the depth of the microchannels created after stainless-steel microneedle roller application. Transdermal flux of both triptans was calculated from the linear portion of the cumulative amount of drug permeated versus time curve. The mean passive flux of almotriptan malate was 13.044 ± 0.32 µg.cm2 .h, while the mean flux following microneedle roller application was 11.281 ± 0.22 µg.cm2 .h. The mean flux values for naratriptan hydrochloride for passive and after microneedle roller application was 0.88 ± 0.29 µg.cm2 .h and 4.18 ± 1.39 µg.cm2 .h, respectively. Statistical analysis was performed using the Student’s t-test (GradPad Prism 7). A statistically significant difference (p\u3c0.05) between microneedle-treated porcine skin samples compared to untreated skin samples was found for the transdermal flux values of naratriptan hydrochloride. Solid stainless-steel microneedle rollers enhanced the transdermal delivery of naratriptan hydrochloride. In contrast, transdermal flux values obtained for almotriptan malate indicate that differences between microneedle-treated and untreated skin samples was not statistically significant (p\u3e0.05)

The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h) compared to passive delivery (12.83 ± 6.30 µg/cm2/h). For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h). Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant

The Response of Caenorhabditis elegans to Hydrogen Sulfide and Hydrogen Cyanide

Hydrogen sulfide (H2S), an endogenously produced small molecule, protects animals from various stresses. Recent studies demonstrate that animals exposed to H2S are long lived, resistant to hypoxia, and resistant to ischemia–reperfusion injury. We performed a forward genetic screen to gain insights into the molecular mechanisms Caenorhabditis elegans uses to appropriately respond to H2S. At least two distinct pathways appear to be important for this response, including the H2S-oxidation pathway and the hydrogen cyanide (HCN)-assimilation pathway. The H2S-oxidation pathway requires two distinct enzymes important for the oxidation of H2S: the sulfide:quinone reductase sqrd-1 and the dioxygenase ethe-1. The HCN-assimilation pathway requires the cysteine synthase homologs cysl-1 and cysl-2. A low dose of either H2S or HCN can activate hypoxia-inducible factor 1 (HIF-1), which is required for C. elegans to respond to either gas. sqrd-1 and cysl-2 represent the entry points in the H2S-oxidation and HCN-assimilation pathways, respectively, and expression of both of these enzymes is highly induced by HIF-1 in response to both H2S and HCN. In addition to their role in appropriately responding to H2S and HCN, we found that cysl-1 and cysl-2 are both essential mediators of innate immunity against fast paralytic killing by Pseudomonas. Furthermore, in agreement with these data, we showed that growing worms in the presence of H2S is sufficient to confer resistance to Pseudomonas fast paralytic killing. Our results suggest the hypoxia-independent hif-1 response in C. elegans evolved to respond to the naturally occurring small molecules H2S and HCN

optical coherence tomography angiography in optic nerve sheath meningioma

This study describes Spectral Domain-Optical Coherence Tomography (SD-OCT) and Optical Coherence Tomography Angiography (OCTA) features of Optic Nerve Sheath Meningioma (ONSM).A 22-year-old woman, diagnosed with meningioma encircling the right optic nerve inside the intraorbital segment optic canal at the magnetic resonance imaging, showed a normal fundus examination.Instead, SD-OCT and OCTA revealed alterations in the neurostructure and microvascular network of the optic nerve.Despite fundoscopy and fluorescein angiography, SD-OCT and OCTA represent valid, non-invasive and reliable methods to evaluate neurostructural and vascular irregularities in this benign tumor of the optic nerve. Keywords: Optic nerve sheath meningioma, OCT angiography, SD-OC

La durabilit\ue0 dei componenti edilizi

La pubblicazione riporta una sintesi dei risultati della ricerca scientifica nazionale (PRIN-2003) su \u201cMetodologie di progettazione e di valutazione della durabilit\ue0 dei componenti edilizi in processi di produzione sostenibili, finalizzate alla programmazione della manutenzione degli edifici\u201d delle sei unit\ue0 di ricerca (Politecnico di Milano, Politecnico di Torino, Universit\ue0 degli Studi Federico II di Napoli, Universit\ue0 degli Studi di Palermo, Universit\ue0 degli Studi di Catania, Universit\ue0 degli Studi di Brescia). La ricerca \ue8 condotta in coerenza con quanto si sta sviluppando a livello internazionale nell\u2019ambito dell\u2019International Council for Research and Innovation in Buiding and Construction (CIB), in particolare nella Commissione CIB W80 Prediction of Service Life of Building Materials and Components, nonch\ue9 nei correlati lavori dell\u2019ISO TC 59 SC14 per l\u2019elaborazione delle varie parti della norma ISO 15686 \u201cService life planning\u201d. Il lavoro ha portato nel 2006 alla uscita della prima norma italiana UNI 11156 \u201cValutazione della durabilit\ue0 dei componenti edilizi\u201d articolata in tre parti: \u201cTerminologia e definizione dei parametri di valutazione\u201d, \u201dMetodi per la valutazione della propensione all\u2019affidabilit\ue0\u201d, \u201dMetodi per la valutazione della durata\u201d. I risultati finora acquisiti costituiscono gi\ue0 un significativo riferimento per gli operatori di committenza pubblica e privata in interventi edilizi di nuova costruzione ai fini di organizzare per essi una manutenzione programmata atta ad assicurare nel tempo il mantenimento di un livello di qualit\ue0 tecnologica adeguato, con benefico effetto di riduzione dei costi di gestione degli edifici. Ci\uf2 potr\ue0 essere perseguito attraverso la conoscenza della qualit\ue0 tecnologica utile dei componenti edilizi dei componenti edilizi richiedibile attraverso le specifiche di durabilit\ue0 direttamente imponibili da parte dei progettisti nei capitolati speciali d\u2019appalto secondo i dettati della sopra citata norma UNI 11156

COMPARING ESTIMATION PROCEDURES FOR DOSE-RESPONSE FUNCTIONS

The dose-response design is often used in agricultural research when it is necessary to measure a biological response at various levels of an experimental factor. This type of problem is common in chemical and pesticide research, however, it can also occur in other disciplines such as plant, animal, soil, and environmental sciences. While the analysis of dose-response data usually involves fitting a regression curve, the primary objective often centers on the estimation of dose related percentiles such as the LD50 or LC50. These measures are useful for comparing the relative efficacy of various treatments, however, the estimation of the specified percentiles is not always straightforward. Traditional methodology has relied on inverted solutions or asymptotic theory for statistical inference. More recently, computer intensive methods have been used to model dose-response relationships and can be more appropriate than traditional methods in some situations. This paper examines both the traditional and modem approaches to estimating doseresponse functions as they apply to binomial data. The techniques will be demonstrated using mortality data collected on black vine weevil eggs exposed to an organic pesticide treatment

A voxel-based morphometry study of disease severity correlates in relapsing–remitting multiple sclerosis

Previous studies have shown a preferential loss of grey matter in fronto-temporal regions in patients with multiple sclerosis. Studies of correlates of disease severity are more controversial, because some studies have suggested an association between sensorimotor cortex atrophy and Expanded Disability Status Scale score, while others did not find such a correlation. The objective of this study was to assess the correlation of regional loss of grey matter and white matter with indexes of clinical and radiological severity in relapsing–remitting multiple sclerosis, including the Expanded Disability Status Scale and lesion load. Correlations between Expanded Disability Status Scale, lesion load and disease duration were assessed in 128 patients with relapsing–remitting multiple sclerosis (Expanded Disability Status Scale range 1.0–6.0) using optimized voxel-based morphometry. Bilateral loss of grey matter in sensorimotor cortices was correlated with Expanded Disability Status Scale, and tissue loss also involved adjacent white matter, extending along pyramidal tracts to the brainstem. Increasing lesion load was correlated with loss of deep grey matter and white matter. No specific region of grey matter or white matter showed a significant correlation with disease duration. These findings support the hypothesis that motor neuron involvement plays a major role in the progression of physical disability. Lesion load accrual affects mainly highly interconnected subcortical structures, while disease duration has a less significant impact on brain atrophy, probably owing to the inter-subject heterogeneity of the clinical course of the disease

Foreign bodies in the upper airways: the experience of two Italian hospitals

OBJECTIVE: To study the pattern of foreign bodies in the upper airways as emerging from the hospital records in the Bologna and Siena hospitals in Italy 1997-2002. METHODS: A retrospective review of hospital records was performed using a standardized protocol. All injuries with ICD9 (International Classification of Diseases, 9'h revision) codes ranging from 931 to 934 which occurred in children age 0-14 were considered for the database. RESULTS: One hundred ninety seven patients were included in the database with a diagnosis of Foreign Bodies (FB) over the study period, 78 with ICD931, 105 with ICD932, 12 with ICD933 and 2 with ICD934 discharge diagnosis. Of the 197 patients, 51.90% of the patients were males and the 48.10% were female. Median age was 4 (2, 6). At the moment of the injury, the child was eating (11%), playing (83%) or studying (4%) or cleaning ears (2%). The child was supervised by an adult in doing his/her activities at the moment of injury in the 84.2% of the cases. The child reached the hospital using always private transport (100%), never by using an emergency transport (0%). Most commonly, FB were extracted in ambulatory (95.4%), more rarely using an endoscopic procedure (4.1%), and never using surgery. Hospitalization was required in the 0.5% of cases (1). CONCLUSIONS: Our study showed the substantial epidemiological similarity of the Italian data with the experience of other center in the world. The burden of chocking was very limited in our country, as proven by the limited access to emergency and more invasive procedures. Nevertheless, some consideration can be made from the preventive point of view. Quite surprisingly, the majority of injuries occurred under the supervision of an adult in playing or recreational activities

Foreign bodies in the upper airways: the experience of two Italian hospitals

OBJECTIVE: To study the pattern of foreign bodies in the upper airways as emerging from the hospital records in the Bologna and Siena hospitals in Italy 1997-2002. METHODS: A retrospective review of hospital records was performed using a standardized protocol. All injuries with ICD9 (International Classification of Diseases, 9'h revision) codes ranging from 931 to 934 which occurred in children age 0-14 were considered for the database. RESULTS: One hundred ninety seven patients were included in the database with a diagnosis of Foreign Bodies (FB) over the study period, 78 with ICD931, 105 with ICD932, 12 with ICD933 and 2 with ICD934 discharge diagnosis. Of the 197 patients, 51.90% of the patients were males and the 48.10% were female. Median age was 4 (2, 6). At the moment of the injury, the child was eating (11%), playing (83%) or studying (4%) or cleaning ears (2%). The child was supervised by an adult in doing his/her activities at the moment of injury in the 84.2% of the cases. The child reached the hospital using always private transport (100%), never by using an emergency transport (0%). Most commonly, FB were extracted in ambulatory (95.4%), more rarely using an endoscopic procedure (4.1%), and never using surgery. Hospitalization was required in the 0.5% of cases (1). CONCLUSIONS: Our study showed the substantial epidemiological similarity of the Italian data with the experience of other center in the world. The burden of chocking was very limited in our country, as proven by the limited access to emergency and more invasive procedures. Nevertheless, some consideration can be made from the preventive point of view. Quite surprisingly, the majority of injuries occurred under the supervision of an adult in playing or recreational activities