No description available.

<p>Background and Aims: While a single &ldquo / high quality&rdquo / oral liquid based cytology (LBC) study has shown a high sensitivity and specificity for the technique in detection of oral dysplasia and malignancy, the high unit cost of this technology cannot be borne by the developing African countries. This study aims to evaluate the efficiency of an alternative cost-effective technique, Shandon PapSpin (PS) LBC in&nbsp / diagnosis of oral and oropharyngeal dysplasia and malignancy. Materials and Methods.We compared the diagnostic accuracy of Shandon PS LBC with that of scalpel biopsy in 69 patients. Transepithelial cytology specimens were obtained using a cervical Cytobrush. The cytology specimens were graded and scored using a novel oral cytologic grading and scoring system respectively. Results: Histological diagnosis of dysplasia or invasive squamous cell carcinoma was made in 51 of the 69 cases. Histology confirmed the cytological diagnosis of dysplasia or malignancy in 49 of the 51 cases. There were two false negative and no false positive cases. The sensitivity was 96% and the specificity 100%. The cytologic grade correlated positively with histologic grade. The best cut off value for distinguishing reactive/mildly dysplastic lesions from high 9 grade/invasive squamous cell carcinoma was determined as a cytologic score of 3, representing a sensitivity of 95% and a specificity of 96%. Conclusion: The Shandon PS LBC in association with transepithelial brush biopsy technique (TBBT) is a highly sensitive, specific and economical screening test in detection of oral and oropharyngeal dysplasia and malignancy. The proposed oral cytologic grading system correlates well with histology. The novel oral cytologic scoring system shows promise as a simple, reliable and reproducible scoring system. In addition, the liquid residual allows for immunocytochemical (Podoplanin) testing.</p>

<p>Background and Aims: While a single &ldquo / high quality&rdquo / oral liquid based cytology (LBC) study has shown a high sensitivity and specificity for the technique in detection of oral dysplasia and malignancy, the high unit cost of this technology cannot be borne by the developing African countries. This study aims to evaluate the efficiency of an alternative cost-effective technique, Shandon PapSpin (PS) LBC in&nbsp / diagnosis of oral and oropharyngeal dysplasia and malignancy. Materials and Methods.We compared the diagnostic accuracy of Shandon PS LBC with that of scalpel biopsy in 69 patients. Transepithelial cytology specimens were obtained using a cervical Cytobrush. The cytology specimens were graded and scored using a novel oral cytologic grading and scoring system respectively. Results: Histological diagnosis of dysplasia or invasive squamous cell carcinoma was made in 51 of the 69 cases. Histology confirmed the cytological diagnosis of dysplasia or malignancy in 49 of the 51 cases. There were two false negative and no false positive cases. The sensitivity was 96% and the specificity 100%. The cytologic grade correlated positively with histologic grade. The best cut off value for distinguishing reactive/mildly dysplastic lesions from high 9 grade/invasive squamous cell carcinoma was determined as a cytologic score of 3, representing a sensitivity of 95% and a specificity of 96%. Conclusion: The Shandon PS LBC in association with transepithelial brush biopsy technique (TBBT) is a highly sensitive, specific and economical screening test in detection of oral and oropharyngeal dysplasia and malignancy. The proposed oral cytologic grading system correlates well with histology. The novel oral cytologic scoring system shows promise as a simple, reliable and reproducible scoring system. In addition, the liquid residual allows for immunocytochemical (Podoplanin) testing.</p>

Magister Chirurgiae Dentium - MChD / Background and Aims: While a single “high quality” oral liquid based cytology (LBC) study has shown a high sensitivity and specificity for the technique in detection of oral dysplasia and malignancy, the high unit cost of this technology cannot be borne by the developing African countries. This study aims to evaluate the efficiency of an alternative cost-effective technique, Shandon PapSpin (PS) LBC in diagnosis of oral and oropharyngeal dysplasia and malignancy. Materials and Methods.We compared the diagnostic accuracy of Shandon PS LBC with that of scalpel biopsy in 69 patients. Transepithelial cytology specimens were obtained using a cervical Cytobrush. The cytology specimens were graded and scored using a novel oral cytologic grading and scoring system respectively. Results: Histological diagnosis of dysplasia or invasive squamous cell carcinoma was made in 51 of the 69 cases. Histology confirmed the cytological diagnosis of dysplasia or malignancy in 49 of the 51 cases. There were two false negative and no false positive cases. The sensitivity was 96% and the specificity 100%. The cytologic grade correlated positively with histologic grade. The best cut off value for distinguishing reactive/mildly dysplastic lesions from high 9 grade/invasive squamous cell carcinoma was determined as a cytologic score of 3, representing a sensitivity of 95% and a specificity of 96%. Conclusion: The Shandon PS LBC in association with transepithelial brush biopsy technique (TBBT) is a highly sensitive, specific and economical screening test in detection of oral and oropharyngeal dysplasia and malignancy. The proposed oral cytologic grading system correlates well with histology. The novel oral cytologic scoring system shows promise as a simple, reliable and reproducible scoring system. In addition, the liquid residual allows for immunocytochemical (Podoplanin) testing. / South Africa

The most popular and convenient route of drug administration remains the oral route, however, protein and peptide drugs such as insulin have poor membrane permeability and stability in the gastrointestinal tract. Absorption enhancers can be added to drug delivery systems to overcome the epithelial cell membrane permeability problem. Although previous studies have shown that aloe leaf materials improve the transport of drugs across intestinal epithelia, their performance in solid oral dosage forms has not yet been investigated. Beads containing insulin and each of the selected absorption enhancers (i.e. Aloe ferox, Aloe marlothii and Aloe vera gel materials) were produced by extrusion-spheronisation, using a full factorial design to optimise the formulations based on transepithelial electrical resistance (TEER) reduction of Caco-2 cell monolayers as response. The optimum bead formulations were evaluated in terms of friability, mass variation, particle surface texture, shape, size and dissolution. The transport of insulin across excised pig intestinal tissue from the optimised bead formulations was determined over a 2 h period. The samples obtained from the transport studies were analysed for insulin content by means of high-performance liquid chromatography (HPLC). The results showed that the TEER reduction, as an indication of tight junction modulation, obtained for the bead formulations containing aloe materials was concentration dependent. Furthermore, inclusion of croscarmellose sodium (Ac-di-sol®) as a disintegrant showed an enhanced TEER reduction effect in combination with the aloe gel materials. Dissolution profiles indicated that the beads containing aloe leaf materials in conjunction with insulin, released the insulin within an hour. In accordance with the TEER reduction results, the A. marlothii and A. vera materials containing beads showed similar increased insulin delivery across excised pig intestinal tissue, which was pronouncedly higher than that of the control group (insulin alone). It can be concluded that beads containing aloe leaf materials have high potential as effective delivery systems for protein therapeutics such as insulin via the oral route of administration. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

The most popular and convenient route of drug administration remains the oral route, however, protein and peptide drugs such as insulin have poor membrane permeability and stability in the gastrointestinal tract. Absorption enhancers can be added to drug delivery systems to overcome the epithelial cell membrane permeability problem. Although previous studies have shown that aloe leaf materials improve the transport of drugs across intestinal epithelia, their performance in solid oral dosage forms has not yet been investigated. Beads containing insulin and each of the selected absorption enhancers (i.e. Aloe ferox, Aloe marlothii and Aloe vera gel materials) were produced by extrusion-spheronisation, using a full factorial design to optimise the formulations based on transepithelial electrical resistance (TEER) reduction of Caco-2 cell monolayers as response. The optimum bead formulations were evaluated in terms of friability, mass variation, particle surface texture, shape, size and dissolution. The transport of insulin across excised pig intestinal tissue from the optimised bead formulations was determined over a 2 h period. The samples obtained from the transport studies were analysed for insulin content by means of high-performance liquid chromatography (HPLC). The results showed that the TEER reduction, as an indication of tight junction modulation, obtained for the bead formulations containing aloe materials was concentration dependent. Furthermore, inclusion of croscarmellose sodium (Ac-di-sol®) as a disintegrant showed an enhanced TEER reduction effect in combination with the aloe gel materials. Dissolution profiles indicated that the beads containing aloe leaf materials in conjunction with insulin, released the insulin within an hour. In accordance with the TEER reduction results, the A. marlothii and A. vera materials containing beads showed similar increased insulin delivery across excised pig intestinal tissue, which was pronouncedly higher than that of the control group (insulin alone). It can be concluded that beads containing aloe leaf materials have high potential as effective delivery systems for protein therapeutics such as insulin via the oral route of administration. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

Master of Science / Department of Biochemistry / Bruce D. Schultz / John M. Tomich / Peptides based on the second transmembrane segment of the glycine receptor (M2GlyR) were made to provide a potential therapeutic treatment for cystic fibrosis (CF) and a latent absorption enhancer for drug delivery. For similarity of presentation, unique synthetic peptide sequences have been given alpha-numeric designations. Results are presented from studies focusing on four peptides. In the first study, the contributions of synthetic peptides p1171, p1172 and p1173 to net transepithelial ion transport were measured as a first step toward the goal of testing whether pore length or electrostatics of pore lining residues will affect anion transport. Peptide p1130 exhibits many attributes that make it an ideal synthetic peptide for CF treatment, but has low permselectivity for anions. Therefore, it is used as a platform for modification. Peptide p1171 is doubly substituted with diaminopropionic acid at positions T13 and T17. Peptide p1172 and p1173 are separately one and two helical turn(s) inserted into the p1130 backbone. Apical exposure of MDCK monolayers to these peptides caused a rapid increase in short circuit current (Isc), an indicator of net ion transport. The increase in Isc caused by p1172 or p1173 was accompanied by increase in transepithelial electrical conductance (gte). The electrophysiological results suggested that these modified peptides can assemble in the apical membrane of epithelial cells to form functional ion-conducting pores. Peptide NC-1059, which provides for ion transport across epithelial cells derived from many sources, was studied further to assess cellular changes that account for increased gte. NC-1059 increased Isc, gte and enhanced permeation of dextrans in a concentration dependent manner. Results from previous and current studies show that NC-1059 modulated the epithelial paracellular pathway by altering the distribution and abundance of junctional proteins. Immunoblotting and immunolabeling with confocal microscopy showed that NC-1059 induces reorganization of actin and causes a reduction in F-actin abundance in epithelial cells. The distributions were changed and cellular abundances were reduced of tight junction proteins occludin and ZO-1 and adherens junction proteins E-cadherin and β-catenin by NC-1059. These effects were largely reversed in 24 hr and fully recovered in 48 hr. Therefore, NC-1059 has the therapeutic potential to increase the efficiency of drug delivery across barrier membranes.

The present investigation is concerned with determining the role of calcium, phospholipids, and phospholipid metabolites on transepithelial sodium and water transport in response to antidiuretic hormone (ADH). These studies utilize the frog skin for determining sodium transport and amphibian urinary bladder for water flow measurements and scanning electron microscopy of cell surface morphology. The results demonstrate that phospholipids and phospholipid metabolites containing arachidonic acid stimulate transepithelial sodium transport through amiloride sensitive channels and the action of these lipids involves the synthesis of prostaglandins. These lipids also inhibited the increase in water flow induced by ADH, and this effect was prevented with prostaglandin synthesis inhibitors. Prostaglandins alter intracellular calcium concentrations and agents effecting calcium metabolism alter cell surface morphology and the changes in surface substructure induced by ADH. These observations support the hypothesis that alterations in membrane permeability to water and ions may involve metabolism of membrane phospholipids and prostaglandin biosynthesis.

No description available.

Epithelia form protective barriers and regulate molecule transport between the mesenchyme and environment. Amongst all metazoans, only sponges are said to lack 'true' epithelia however the physiology of sponge cell layers are rarely studied empirically. Aggregates and gemmules of a freshwater demosponge, Spongilla lacustris, were used to grow confluent tissue over permeable culture wells which are required for transepithelial recordings. The transepithelial potential (TEP) of S. lacustris was slightly negative (-3mV), indicating possible control of ion transport. Transepithelial resistance (TER) was recorded between 1-2 k cm2, the same order of magnitude as many vertebrate epithelia. Cultures with high resistance blocked the passage of the small tracer molecules 14C-PEG, 3H-Inulin and ruthenium red. Pinacocytes were spatially stable over time and epithelial layers were morphologically similar in freshwater and marine species. These results suggest that sponge cell layers are able to control solute and ion transport, the physiological attributes of functional epithelia. / Physiology, Cell and Development Biology