Template Assisted Formation of 32 and 34π Octaphyrins Embedded with Dithienopyrrole Cores: A New Scaffold to Unravel Proton Coupled Redox Switching and (Anti)Aromaticity.

Herein, we report two distinct octaphyrins obtained by the condensation of new dithieno[3,2-b:2',3'-d]pyrrole based tetrapyrrane under two different acidic conditions. Fourfold meso-substituted octaphyrin was the major product when the reaction was performed in the presence of an aryl aldehyde using trifluoroacetic acid. Whereas, the sixfold meso-substituted octaphyrin was obtained when the precursor was condensed with pentafluorobenzaldehyde using para-toluenesulfonic acid. Such a template effect of aryl aldehydes in oxidative coupling reactions is realized for the first time in literature. Experimental and theoretical studies suggested that the oxidized form of fourfold meso-substituted octaphyrin is 32π antiaromatic and undergoes proton-coupled electron transfer (PCET) to the protonated form of 34π aromatic congener upon treatment with protic acids. Furthermore, small organic molecules such as alcohols and amines were also found to promote chemical reduction. Single crystal X-ray structure revealed that the aromatic counterpart is highly planar and stabilized by several intermolecular H-bonding and F-F interactions, leading to a large 3D supramolecular arrangement and exhibited colorimetric sensing for fluoride and hydroxide anions. On the other hand, sixfold meso-substituted octaphyrin did not show (anti)aromatic features, PCET or anion sensing, but its intriguing absorption features associated with protonation could make it an ideal candidate for pH-dependent bioimaging.

Predictors of pituitary tumour behaviour: an analysis from long-term follow-up in 2 tertiary centres.

OBJECTIVES: To determine the clinical utility of assessment of tumour invasion, markers of proliferation, and the French clinicopathological classification in pituitary tumour prognostication. METHODS: This is a retrospective evaluation of adult patients undergoing pituitary surgery at Oxford University and St Vincent's Hospitals, between 1989 and 2016, with at least 12 months of clinical data. Invasion was assessed radiologically, proliferative markers (Ki67, mitotic count, p53) by immunohistochemistry. Tumours were graded according to the clinicopathological classification. Intra- and interlaboratory variability of histopathology reporting was evaluated. OUTCOMES: (1) Tumour recurrence (radiological or reintervention ≥12 months postoperatively) and/or (2) "aggressive behaviour" (≥4 interventions and/or invasive tumour with recurrence/reintervention between 12 and 24 months postoperatively). RESULTS: A total of 386 patients were included, age at surgery was 56 (interquartile range [IQR] 41-67) years, 54% were male, and median follow-up was 90 months (range 44-126). Tumours were predominantly clinically nonfunctioning (252, 65%), with overall 53% invasive, and 10% that demonstrated ≥2 proliferative marker positivity. Recurrence was predicted by invasiveness (hazards ratio [HR] 1.6 [1.10-2.37], P .02), elevated mitotic count (HR 2.17 [1.21-3.89], P .01), grade (2b vs 1a HR 2.32 [1.06-5.03], P .03), and absence of gross total resection (HR 3.70 [1.72-8.00], P .01). Clinically defined aggressiveness was associated with elevated Ki67, mitotic count, and invasiveness. Ki67 reporting methodologies showed moderate correlation across laboratories (Phi 0.620), whereas p53 reporting reproducibility was poor (Phi 0.146). CONCLUSIONS: Proliferative markers, including Ki67 and mitotic count, but not p53, are important in predicting the development of aggressive pituitary tumour behaviour.

Comparison of Indirect Fungal Diagnostic Tests in Patients With Proven Histoplasmosis.

Background: Histoplasmosis is a common cause of invasive fungal infection in endemic regions and accurate diagnosis is difficult without direct tissue culture or pathology. Indirect fungal antigen testing for various fungal pathogens are typically performed to assist with diagnostic workup, though cross-reaction can lead to difficulty in interpreting results. We aimed to compare indirect fungal diagnostic tests and evaluate prevalence of positive antigen testing for non-Histoplasma fungal pathogens in patients with proven histoplasmosis. Methods: We performed a single-center retrospective review of adult patients with proven histoplasmosis diagnosed by fungal culture and/or cytology from January 2010 to March 2018. Patient demographics, clinical characteristics, and results of fungal antigen testing for Histoplasma, Blastomyces, Aspergillus, Cryptococcus, and (1→3)-ß-D-glucan were evaluated. Two different urine Histoplasma antigen assays were used during the study period. Results: Fifty-seven of 182 (31.3%) patients reviewed had proven histoplasmosis and presented with acute pulmonary (n = 10), chronic pulmonary (n = 7), and disseminated (n = 40) disease. Forty-one (72%) of these patients were immunosuppressed. Urine Blastomyces antigen (93%) and serum (1→3)-ß-D-glucan (88%) were commonly positive in patients with histoplasmosis, whereas Aspergillus antigen was detected in 50% of patients and Cryptococcus antigenemia was rare (5%). In patients with disseminated disease, the MiraVista urine Histoplasma antigen assay had higher sensitivity than the Viracor urine Histoplasma antigen assay (86% vs 50%, respectively; P = .019). Conclusions: Noninvasive fungal antigen assays are helpful diagnostic tools; however, given their low specificity, clinicians must be aware of the various clinical presentations of invasive fungal infections and be aware of the limitations of these tests.

Timing and sequencing of oro-pharyngeal swallow events in persistent dysphagia post-stroke / Momento y secuencia de los eventos de deglución orofaríngea en la disfagia persistente post-ictus

Introduction and objectives: Evidence from videofluoroscopic analysis of healthy swallowing physiology shows that typical swallowing function is not entirely ‘sequential’ but are clusters of precisely coordinated movements. It is unknown if disruption of this fine orchestra of events could be associated with persistent dysphagia in individuals post-stroke. This investigation studied the time of onset and sequencing of specific oro-pharyngeal swallowing events as seen in the modified barium swallow study in a population with airway penetration of swallowed bolus post-stroke. Materials and methods: A retrospective frame to frame analysis of 29 time points in single cued 5ml liquid barium swallows obtained from 23 individuals who satisfied inclusion criteria was conducted independently by two investigators. Relative temporal measures with reference to upper esophageal sphincter activity were calculated. Results and conclusion: Statistical analysis revealed five temporal clusters of swallowing events while the onset of oral bolus transport, soft palate elevation, upper esophageal sphincter opening, hyoid descent, and complete laryngeal closing occurred independently. A timeline of event sequences was also developed that showed multiple deviations from the known sequences reported in healthy swallowing literature. There was a delay as well as deviance from known normality in the order of swallowing events considered in this study. The findings suggested a difference in the underlying programming for a swallow in post-stroke dysphagia, that may also contribute to the airway intrusion. The study provides preliminary evidence for the inclusion of temporal measures of swallowing physiology during an instrumental assessment of swallowing function in persons with dysphagia.(AU)

Introducción y objetivos: La evidencia del análisis videofluoroscópico de la fisiología de la deglución saludable muestra que la función de la deglución típica no es completamente «secuencial», sino que son grupos de movimientos coordinados con precisión. Se desconoce si la interrupción de esta fina armonía de eventos podría asociarse con una disfagia persistente en individuos después del accidente cerebrovascular. Esta investigación estudió el tiempo de inicio y la secuenciación de eventos específicos de deglución orofaríngea, como se observa en el estudio modificado de deglución de bario en una población con penetración de las vías respiratorias del bolo ingerido después del accidente cerebrovascular. Materiales y métodos: El análisis retrospectivo paso a paso de 29 momentos de la deglución de 5ml de bario líquido analizados en 23 individuos que cumplieron con los criterios de inclusión fue realizado de forma independiente por dos investigadores. Se calcularon medidas temporales relativas a la actividad del esfínter esofágico superior. Resultados y conclusiones: El análisis estadístico reveló cinco grupos temporales de eventos de deglución, mientras que el inicio del transporte de bolo oral, la elevación del paladar blando, la apertura del esfínter esofágico superior, el descenso de hioides y el cierre laríngeo completo se produjeron de forma independiente. También se desarrolló una línea de tiempo de secuencias de eventos que mostraba múltiples desviaciones de las secuencias conocidas reportadas en la literatura de deglución saludable. Hubo un retraso, así como una desviación de la normalidad en el orden de los eventos de deglución considerados en este estudio. Los hallazgos sugirieron una diferencia en la programación subyacente para una deglución en la disfagia tras el accidente cerebrovascular, que también puede contribuir a la intrusión de las vías respiratorias.(AU)

Persistent Methicillin-Susceptible Bacteremia Rapidly Cleared with Cefazolin and Ertapenem Combination Therapy in a Patient with COVID-19.

Methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) are associated with significant morbidity and mortality. MSSA BSIs can rapidly disseminate, resulting in deep-seated infections, prolonged durations of bacteremia, and further metastases. Recently, cefazolin and ertapenem combination therapy has emerged as a potential therapeutic strategy to sterilize the blood in patients with persistent MSSA bacteremia. Here, we present a patient with COVID-19 pneumonia and concomitant MSSA BSI achieving blood culture sterilization within 24 hours of cefazolin and ertapenem combination therapy initiation following 11 days of positive blood cultures.

Triple Intussusception in an Adult-A Rare Presentation of Adenocarcinoma Ileum.

Intestinal intussusception is uncommon in adults. It occurs more often in the small intestine than in the colon. In adults, when small bowel intussusception occurs, it can be due to a malignant lead point. Malignant etiology is most frequently due to diffuse metastatic disease. We present a rare case of an 18-year-old woman who was diagnosed with jejunojejunal, jejunoileal, and colocolic intussusceptions. She presented with vomiting, abdominal pain, and passage of semisolid stools for 5 days. During emergency exploratory laparotomy, multiple polyps were found in the jejunum, ileum, and sigmoid. Jejunotomy and sigmoidotomy were done to remove the respective polyps. The ileal polyp showed hemorrhagic changes; hence, an intraoperative decision was taken to proceed with resection and anastomosis. On histopathological examination, the resected ileal part showed moderately differentiated adenocarcinoma (grade 2) arising from an adenomatous polyp, while the jejunal polyp and sigmoid polyp were adenomatous polyps with low-grade dysplasia. Patient received six cycles of adjuvant chemotherapy consisting of capecitabine and oxaliplatin (CAPEOX regimen). After 2 years, she is symptom free with a normal colonoscopy. The treatment of intussusception in adults typically involves surgery, often with bowel resection as there is always a pathologic leading cause which may be malignant, like in our case.

Spontaneous Bacterial Peritonitis Caused by Bordetella hinzii.

Although Bordetella hinzii coccobacilli is most commonly identified in respiratory tracts of birds and rodents, this organism has occasionally been isolated in human infections. We describe a case of B. hinzii spontaneous bacterial peritonitis in Missouri, USA. Whole-genome sequencing of blood and peritoneal fluid isolates confirmed B. hinzii infection.

Comparison of Blood (1->3)-ß-d-Glucan Levels in AIDS-Related Pneumocystis jirovecii Pneumonia and AIDS-Related Progressive Disseminated Histoplasmosis.

In this retrospective study, (1->3)-ß-d-glucan (B-glucan) was an unreliable marker for AIDS-related Pneumocystis jirovecii pneumonia (PCP) because a high percentage of participants with progressive disseminated histoplasmosis and respiratory symptoms had a positive B-glucan result. Where histoplasmosis is common, attributing B-glucan positivity to PCP without further testing risks misdiagnosis.

How can gastro-intestinal tuberculosis diagnosis be improved? A prospective cohort study.

BACKGROUND: Gastrointestinal tuberculosis (TB) is diagnostically challenging; therefore, many cases are treated presumptively. We aimed to describe features and outcomes of gastrointestinal TB, determine whether a clinical algorithm could distinguish TB from non-TB diagnoses, and calculate accuracy of diagnostic tests. METHODS: We conducted a prospective cohort study of hospitalized patients in Kota Kinabalu, Malaysia, with suspected gastrointestinal TB. We recorded clinical and laboratory characteristics and outcomes. Tissue samples were submitted for histology, microscopy, culture and GeneXpert MTB/RIF®. Patients were followed for up to 2 years. RESULTS: Among 88 patients with suspected gastrointestinal TB, 69 were included in analyses; 52 (75%) had a final diagnosis of gastrointestinal TB; 17 had a non-TB diagnosis. People with TB were younger (42.7 versus 61.5 years, p = 0.01) and more likely to have weight loss (91% versus 64%, p = 0.03). An algorithm using age < 44, weight loss, cough, fever, no vomiting, albumin > 26 g/L, platelets > 340 × 109/L and immunocompromise had good specificity (96.2%) in predicting TB, but very poor sensitivity (16.0%). GeneXpert® performed very well on gastrointestinal biopsies (sensitivity 95.7% versus 35.0% for culture against a gold standard composite case definition of confirmed TB). Most patients (79%) successfully completed treatment and no treatment failure occurred, however adverse events (21%) and mortality (13%) among TB cases were high. We found no evidence that 6 months of treatment was inferior to longer courses. CONCLUSIONS: The prospective design provides important insights for clinicians managing gastrointestinal TB. We recommend wider implementation of high-performing diagnostic tests such as GeneXpert® on extra-pulmonary samples.

A Systematic Review of the Influence of Bolus Characteristics on Respiratory Measures in Healthy Swallowing.

There have been a number of studies on the effect of bolus volume, consistency, texture, temperature and taste on the oropharyngeal swallowing physiology. However, its influence on the respiratory function associated with swallow is not well understood. This study aimed at systematically analysing and documenting the prevailing research literature on respiratory functions before, during, and after healthy swallows of boluses with varied characteristics. The PRISMA guidelines were followed for retrieval of relevant research. From among the 48,329 reports screened for inclusion criteria, 25 articles were included for data extraction. Each of these reports was evaluated for its design, methodology and reporting quality and also the level of evidence provided by them. The results revealed that the scientific evidence in this regard was restricted to level II. Majority of the studies included considered bolus volume as the variable than bolus consistency, taste or temperature. Expiratory phase was preferred surrounding the apnea irrespective of volume, consistency or taste but changed with temperature variations across age groups. The reports are equivocal on the duration of respiratory apnea, and length of respiratory cycles before and after the apnea. The temporal coordination of pharyngeal swallow events was found to be independent of bolus volume. This review concluded that bolus characteristics have differential effects on the respiratory functions during swallow beyond a 'central sensory threshold' level. Objective standardization of bolus characteristics may be the immediate requirement for generalization of future research findings in this direction.

Candidal carriage in saliva and subgingival plaque among smokers and non-smokers with chronic periodontitis-a cross-sectional study.

BACKGROUND AND OBJECTIVES: Studies of gum or periodontal disease have focused mainly on bacterial pathogens. However, information related to fungal species in the saliva and subgingival mileu is particularly lacking in smokers with periodontitis. This cross-sectional study compared the prevalence of various Candida species in saliva and subgingival plaque samples of smokers and non-smokers with periodontal disease. METHODOLOGY: Study subjects were recruited into three group-Group 1: Smokers with chronic periodontitis (N = 30), Group 2: Non-smokers with chronic periodontitis (N = 30) and Group 3: Healthy controls (N = 30). Clinical parameters recorded included plaque index (PI), gingival index (GI), periodontal probing depth (PPD) and clinical attachment loss (CAL). Saliva and subgingival plaque samples were collected from subjects from the above groups. The collected samples were processed for isolation and identification of various Candida species using CHROMagar chromogenic media. Additionally, antifungal susceptibility tests were performed for the isolated Candida species in order to assess antifungal drug resistance to fluconazole and voriconazole. RESULTS: Prevalence of Candida species in saliva samples was quantified as 76.6% in Group 1, 73.3% in Group 2 and 36.6% in Group 3 and statistically significant differences were observed between groups 1 & 3. Prevalence of Candida species in subgingival plaque samples was quantified as 73.3% in Group 1, 66.6% in Group 2 and 60% in Group 3 and no statistically significant differences were observed between groups. Candida albicans was the most frequently isolated species followed by Candida krusei and Candida tropicalis. A positive correlation was observed for smoking exposure, pack years and Candida colonization. A marginally significant positive correlation was observed between Candida colonization and increasing pocket depth and attachment loss. Antifungal drug resistance was mainly observed for Candida krusei in both saliva and subgingival plaque samples. CONCLUSION: Based on the results we can conclude that oral candidal carriage is significantly increased in smokers with periodontal disease. Mechanistic studies are needed to understand the importance of Candida species in periodontal disease.

Prevalence of Vitamin B12 Deficiency and its Associated Factors among Patients with Type 2 Diabetes Mellitus on Metformin from a District in Malaysia.

INTRODUCTION: Vitamin B12 deficiency is more common among metformin-treated subjects although the prevalence is variable. Many factors have been associated with this. The aim of this study is to determine the prevalence of vitamin B12 deficiency and its associated factors among patients with type 2 diabetes mellitus (DM) who are on metformin. METHODOLOGY: A total of 205 patients who fit eligibility criteria were included in the study. A questionnaire was completed, and blood was drawn to study vitamin B12 levels. Vitamin B12 deficiency was defined as serum B12 level of ≤300 pg/mL (221 pmol/L). RESULTS: The prevalence of vitamin B12 deficiency among metformin-treated patients with type 2 DM patients was 28.3% (n=58). The median vitamin B12 level was 419 (±257) pg/mL. The non-Malay population was at a higher risk for metformin-associated vitamin B12 deficiency [adjusted odds ratio (OR) 3.86, 95% CI: 1.836 to 8.104, p<0.001]. Duration of metformin use of more than five years showed increased risk for metformin-associated vitamin B12 deficiency (adjusted OR 2.06, 95% CI: 1.003 to 4.227, p=0.049). CONCLUSION: Our study suggests that the prevalence of vitamin B12 deficiency among patients with type 2 diabetes mellitus on metformin in our population is substantial. This is more frequent among the non-Malay population and those who have been on metformin for more than five years.

Hyperthyroidism presenting as ST Elevation Myocardial Infarction with Normal Coronaries - A Case Report.

A 31-year-old male, apparently well, presented with typical chest pain. His ECG showed ST-elevation from V1-V4 and echocardiogram revealed anteroseptal wall hypokinesia with ejection fraction of 45%. Normal coronary arteries were seen on coronary angiogram. A thyroid function test showed elevated free T4 levels with suppressed thyroid stimulating hormone (TSH). Treatment with thionamides and beta-blockers improved symptoms. Upon review 4 months later he was well. Repeat echocardiogram showed good ejection fraction with no hypokinetic area.

Case Report of an Adult Female with Neglected Congenital Adrenal Hyperplasia (CAH).

An apparently well 27-year-old phenotypically male adult was seen at the endocrine clinic for gender assignment. Patient had been raised as a male and identifies as such. Abdominal CT scan showed a unilateral left adrenal mass and karyotyping revealed 46 XX female karyotype. She was diagnosed to have simple virilizing CAH and needed thorough counselling with subsequent management by a multidisciplinary team.

Efficacy of Four Remineralizing Agents on Primary Teeth: In Vitro Evaluation Using Microhardness Testing and Quantitative Light-induced Fluorescence.

PURPOSE: This study's purpose was to evaluate the remineralization of primary enamel using GC Tooth Mousse, Clinpro Tooth Crème, SHY-NM, and Pronamel by employing microhardness testing and quantitative light-induced fluorescence (QLF) values. METHODS: An in vitro study was performed with 100 intact primary anterior teeth. After specimen preparation, they were subjected to baseline microhardness and QLF testing. The specimens were immersed in demineralizing solution, subjected again to microhardness and QLF testing, and divided randomly into five groups of 20 teeth: group one-control group (artificial saliva); group two-GC Tooth Mousse; group three-ClinPro tooth crème; group four-SHY-NM; and group five-Pronamel. The pastes were respectively applied for the specific group specimens for 15 consecutive days. The samples were subjected to microhardness and QLF testing. RESULTS: The results were analyzed using analysis of variance testing. A post-hoc comparison was done using a paired t test. There were mean increases in microhardness and QLF values with all remineralizing agents. Group two showed a statistically significant increase (P<0.05) in microhardness and QLF values. Group four showed a significant increase only in microhardness values. (P<0.05). CONCLUSION: GC Tooth Mousse and SHY-NM are promising materials for remineralizing incipient lesions in primary teeth.

Immune checkpoints and immunotherapy for colorectal cancer.

Colorectal cancer (CRC) remains one of the major causes of death worldwide, despite steady improvement in early detection and overall survival over the past decade. Current treatment paradigms, with chemotherapy and biologics, appear to have reached their maximum benefit. Immunotherapy, especially with checkpoint inhibitors, has shown considerable clinical benefit in various cancers, including mismatch-repair-deficient CRC. This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents-as single agents, combinations and in conjunction with chemotherapy-in patients with CRC. This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC, as well as current efforts in CRC immunotherapy.

Iontophoretic skin permeation of peptides: an investigation into the influence of molecular properties, iontophoretic conditions and formulation parameters.

The transdermal route offers advantages for delivery of peptides and proteins. However, these polar and large molecules do not permeate the skin barrier well. Various enhancement methods have been employed to address this problem. Iontophoresis is one of the methods that shows promise but its application to peptide delivery has yet to be fully explored. This study investigates the effects of different molecular properties and iontophoretic conditions on the skin permeation of peptides. In this study, the permeation of alanine-tryptophan dipeptide (MW 276 Da), alanine-alanine-proline-valine tetrapeptide (MW 355 Da), Argireline® (Acetyl hexapeptide-3, MW 889 Da) and Triptorelin acetate (decapeptide, MW 1311 Da) through excised human skin under passive or iontophoretic current of 0.4 mA was investigated. The effects of pH change (3.0-7.4, to provide different net negative, neutral, and positive charges) to the peptide, donor concentration (1-10 mg/ml), background electrolyte (34-137 mM NaCl and/or 5-20 mM HEPES) and current direction (anodal vs cathodal) were also studied. Peptides were analysed by high-performance liquid chromatography or liquid scintillation counting. Iontophoresis led up to a 30 times increase in peptide permeation relative to passive permeation for the peptides. Electroosmosis was an important determinant of the total flux for the high molecular weight charged peptides. Electrorepulsion was found to be considerable for low molecular weight charged moieties. Permeation was decreased at lower pH, possibly due to decreased electroosmosis. Results also showed that 10 times increase in donor peptide concentration increases permeation of peptides by about 2-4 times and decreases iontophoretic permeability coefficients by about 2.5-5 times. The addition of extra background electrolyte decreased the iontophoretic permeation coefficient of peptides by 2-60 times. This study shows that iontophoretic permeation of peptides is affected by a number of parameters that can be optimized for effective transdermal peptide delivery.

Enhanced sonophoretic delivery of 5-aminolevulinic acid: preliminary human ex vivo permeation data.

BACKGROUND/AIMS: 5-Aminolevulinate (ALA) is an important photodynamic therapy drug for the treatment of actinic keratoses and other non-melanoma skin cancers in cosmetically sensitive areas. One limitation of this drug is a relatively high recurrence rate. Our aim was to evaluate the feasibility of ultrasound augmented ALA delivery in excised human skin. MATERIALS AND METHODS: An ultrasonic delivery device was used to enhance radiolabelled ALA into excised skin. Quantification of ALA was performed after passive and ultrasonic ALA delivery. Transepidermal water loss was used as a measure of barrier function before and after ultrasonic treatment. RESULTS: We found that ultrasonic treatment dramatically increased the mean cumulative amount of ALA to P< 0.0001 from 4 to 8 h when compared to passive ALA treatment. The flux was calculated to be 54.8 ± 8.0 µg/cm(2) h with ultrasound treatment. TEWL increased nearly two-fold, from 12.3 to 21.0, after ultrasound treatment. CONCLUSION: Our study supports the use of ultrasound for improved ALA delivery by showing significant improvements in the cumulative drug load and flux via combined ultrasound and ALA treatment.

Enhanced transdermal delivery of 5-aminolevulinic acid and a dipeptide by iontophoresis.

Poor skin permeability limits the application of peptides to the skin. Enhanced skin permeation could facilitate the development of new therapies for dermatologic and cosmeceutical applications. The aim of this study was to investigate the application of iontophoresis to the delivery of small peptide model compounds (5-aminolevulinic acid and L-alanine-L-tryptophan) across human skin. Under the conditions tested, iontophoresis increased the in vitro permeability coefficient of ALA.HCl across human epidermis from 7 X 10(-5) cm/h with passive diffusion to 110 x 10(-5) cm/h with iontophoresis. D-Glucose permeation elucidated the iontophoretic electrotransport of ALA.HCl to have contributions of both electrorepulsion and electroosmosis. The L-alanine-L-tryptophan permeability coefficient was increased from 1.5 x 10(-5) cm/h to 35 x 10(-5) cm/h with iontophoretic application. Iontophoretic delivery of the dipeptide increased markedly at lower pH because of an increase in electrorepulsive transport. The study demonstrates that iontophoresis can enhance epidermal permeation of a small peptide and peptide-like drug by up to 15- and 22-fold under the conditions tested.

Enhanced skin permeation and hydration by magnetic field array: preliminary in-vitro and in-vivo assessment.

OBJECTIVES: The aim of the study was determine the effect of magnetic film array technology on the skin permeation of urea. METHODS: A 5% urea gel was applied to human epidermal membrane in vitro and human skin in vivo. Application of gel with magnetic film array and plastic occlusive film was compared with application of gel with a plastic occlusive film and non-magnetic film. In-vitro epidermal penetration was determined using a Franz-type diffusion system. In-vivo permeation and changes in epidermal properties were visualised by optical coherence tomography. KEY FINDINGS: The mean cumulative permeation of urea over 2 h for magnetic film array application was 89.54 +/- 7.34 microg/cm(2) as compared with 20.83 +/- 2.02 microg/cm(2) for passive occluded application (mean +/- SEM, n = 9/8), representing greater than 4-fold increase over the 2-h application time period. Administration of urea with the magnetic film array resulted in the lag time being reduced from 40.58 +/- 3.98 to 21.13 +/- 6.27 min (P < 0.02), while steady state flux increased from 0.24 +/- 0.03 to 0.75 +/- 0.06 microg/cm(2) per min (P < 0.0001). Under active occlusion, the relative change in epidermal thickness as determined by optical coherence tomography increased by 16 and 11% at 30 and 60 min, respectively. CONCLUSIONS: Administration with a novel magnetic film array technology provided enhanced skin penetration of urea and increased epidermal hydration when compared with administration under an occlusive film only.