Mechanisms and solutions for nasal drug delivery - a narrative review.

The aim of this paper is to review mechanisms and solutions for nasal drug delivery. Literature survey was performed via PubMed, Google Scholar, Google, and ProQuest Central database of Kirikkale University. The nasal lining presents a large area of endothelium of variable permeability and with a rich vascular supply. Advantages of this route include eliminating first-pass metabolism and being easily accessible. The nasal route enables some agents which are otherwise difficult to administer to enter the systemic circulation, for example, low molecular mass compounds with high polarity, peptides, or proteins. There are three principal factors that influence the extent to which drugs can be absorbed through the nasal lining, namely the physico-chemical characteristics of the drug molecule itself, the action of the mucociliary system within the nose, and the presence of any factors increasing nasal absorption. A key factor limiting the use of the intranasal route of administration is insufficient absorption through the nasal mucosa. A number of drugs in development cannot be administered intranasally because their bioavailability following nasal administration is too low. There has been considerable research focus on methods to enhance absorption via the nasal mucosa. In this chapter, we review the literature related to this problem and discuss potential solutions.

Could COVID-19 improve psychiatric awareness at the heart of the Middle East? - A personal reflection on Bahrain's response.

This perspective offers a personal insight into COVID-19 in Bahrain along with the response to this unprecented pandemic. In a country where a robust health care system and economic prosperity have allowed it to cope with the medical sequelae, the mental health consequences may have been less anticipated but more problematic. An unforeseen positive emerging from the pandemic might be the nation's recognition of the importance of mental health well-being and a new openness to discussing it.

The theory of a "staphylococcus superantigen" in chronic rhinosinusitis with nasal polyps: myth or reality?

OBJECTIVE: The aim of our study was to search for evidence of a "staphylococcus superantigen" in chronic rhinosinusitis with nasal polyps. PATIENTS AND METHODS: Sixty-nine patients with chronic rhinosinusitis with nasal polyps and 45 healthy controls were included in the study. All patients in the study and control groups underwent bacteriological and immunological examination on nasal smear samples. Total IgE and the following cytokines were tested in all patients: tumor necrosis factor (TNF), interleukin-1 (IL1), interleukin-6 (IL6), interleukin-8 (IL8). RESULTS: The concentration of bacteria in the nasal cavity was much higher in patients in the study group compared to those in the control group, mainly due to staphylococci. In species identification of staphylococci, bacteria most represented were S. aureus and S. epidermidis. The greater the concentration of S. aureus, the lower the level of IgE. Proinflammatory cytokines were uniformly increased in patients with nasal polyps. The level of IgE was maximal in patients with chronic rhinosinusitis with nasal polyps with a poor growth of culture and minimal in patients with abundant growth, suggesting that in the latter the effect of eosinophilic inflammation on the disease was reduced, and conversely, the activity of eosinophilic inflammation was maximal with a poor seeding of the nasal cavity. CONCLUSIONS: Although this study has some limits, our findings do not support the theory of a staphylococcus superantigen in which the IgE level and eosinophilic inflammation should increase with increasing activity of Staphylococcus aureus. Further research supported by a larger sample of patients is required to better delineate the role of a staphylococcus superantigen in the pathogenesis of patients with chronic rhinosinusitis with nasal polyps.

Laser-assisted uvulopalatoplasty: post operative complications (NILES, preliminary experience).

Laser (CO(2)) assisted uvulopalatoplasty (LAUP) is an out-patient technique under local anesthesia, proposed for the treatment of snoring. The National Institute of Laser Enhanced Sciences, Cairo University, began to offer (LAUP) to patients since summer 1996. A patient survey was developed to evaluate the postoperative complications. A total of 60 post-treatment surveys were completed using a written questionnaire or telephone calls at intervals ranging between day 1 and 6 months. Complications ranged from allergy to local anesthesia to severe pain. No serious complications were recorded. Further long run study is necessary for full understanding and assessment.

Characterization of fucosyllactose determinant-bearing glycoproteins probed by a Biomphalaria alexandrina lectin in Schistosoma mansoni cercariae.

Utilizing a Biomphalaria alexandrina-derived lectin (BaSII) of proven specificity to a Schistosoma mansoni-associated fucosyllactose [(Fuc alpha 1-2) Gal beta 1-4 Glc] determinant, two determinant-bearing glycoproteins of 40 and 37 kDa were found to be synthesized by the cercarial stage of the parasite. The two glycoproteins were isolated by BaSII affinity column chromatography from extracts of cercariae metabolically radiolabelled with 35S-methionine. Treatments with endoglycosidases, alkaline borohydride, as well as concanavalin A column chromatography and analysis by two-dimensional gels indicated that the two glycoproteins are synthesized as a single 33 kDa polypeptide backbone that is differentially glycosylated with one and/or two determinant-bearing N-linked complex-type glycan units of either the biantennary, or, to a lesser extent, the tri- or tetra-antennary types. The two glycoproteins lack other conventional high mannose-type or O-linked glycans, and the distinct structures of the complex-type oligosaccharides accounted solely for the expression of three isomorphs for each determinant-bearing glycoprotein. Based on the structural relatedness of the fucosyllactose determinant to the antigenic mammalian blood group H trisaccharide, our observations may have implications in mechanisms of host-parasite interactions as well as immunoprophylaxis.

Structural characterization of an Lyt-2/3 homolog expressed on Bufo regularis lymphocytes.

Two alloantisera and a monoclonal antibody (mAb 53-6.7) of proven specificities to the murine Lyt-2/3 macromolecule labeled, in indirect immunofluorescent assays, a distinct lymphocyte population in the toad, Bufo regularis. Lyt-2/3 antigenic activities expressed by B. regularis lymphocytes have been solubilized and purified by mAb 53-6.7 affinity chromatography and found to be associated with a single 67 kDa macromolecule in SDS-PAGE. Upon reduction, this macromolecule resolved into 38 kDa, 34 kDa and 28 kDa subunits corresponding to the alpha, alpha' and beta subunits of the murine Lyt-2/3 complex. Comparisons based on the S delta Q index of differences in amino acid compositions of HPLC-purified alpha- and alpha'-subunits of the amphibian Lyt-2/3 molecule indicated a significant structural relatedness to their murine counterpart as well as to the human CD8 polypeptide. Our observations point to an early phylogenetic emergence of Lyt-2/3 as an important component of the T cell cytolytic apparatus during vertebrate evolution.

Characterization of Biomphalaria alexandrina-derived lectins recognizing a fucosyllactose-related determinant on schistosomes.

Two novel lectins that bind selectively to a schistosome-associated fucosyllactose-related determinant have been characterized and purified from the hemolymph of Biomphalaria alexandrina, the snail vector of Schistosoma mansoni. Both lectins were purified by affinity chromatography on a column of equimolar mixture of D- and L-glucose coupled to epoxy-activated Sepharose 6B and sequential elution by D-glucose (designated BaSI) and L-fucose (designated BaSII). Assessment of the structural characteristics, by one- and two-dimensional polyacrylamide gel electrophoresis, indicated that BaSI and BaSII were structurally distinct, and exist in their native forms as multimers of non-covalently associated subunits, that were of different sizes in BaSI and of equal size in BaSII. Removal of N-linked glycans by Endo-beta-N-acetylglucosaminidase F resolved the heterodisperse pattern of BaSI subunits into two spots of 13.2 kDa (pI 7.2) and 10.1 kDa (pI 5.8), and collapsed the acidic charge microheterogeneity of the BaSII subunit into a single spot that corresponded in terms of molecular weight and pI to the basic 13.2-kDa subunit of BaSI. In miracidial binding and inhibition assays with different sugars, both lectins exhibited selectivity towards a fucosyllactose sequence, but BaSII had a higher binding preference to fucose moieties. BaSII-Sepharose 4B affinity chromatography and analysis on two-dimensional gels indicated that multiple copies of the fucosyllactose-related determinant were expressed by heterogeneous, acidic glycoproteins in the miracidial stage of S. mansoni.

Identification of peanut agglutinin-binding glycoproteins on lizard lymphocytes.

The expression of PNA-binding glycoproteins on lizard lymphocytes was investigated by studying the reactivity of FITC-PNA towards lizard lymphocytes obtained from the different lymphoid organs. Direct immunofluorescence assays have demonstrated that the majority of lizard thymocytes (70%) and only a fraction of lymphocytes in the spleen, peripheral blood and bone marrow were PNA-positive. This positivity was selectively inhibited by galactose as well as lactose, indicating the specificity of binding. Putative PNA receptors were purified from lizard thymocytes and splenocytes by affinity chromatography on a PNA-Sepharose 4B column and resulted in fractions enriched 1,792-fold and 3,141-fold for the PNA-binding component expressed on lizard thymocytes and splenocytes, respectively. Analysis on reducing and non-reducing SDS-PAGE revealed that both thymic and splenic PNA-binding glycoproteins migrated as a single component of 35 KDa, with no evidence for the association into higher multimers in both tissues. Analyses for amino acid and carbohydrate compositions indicated that the thymic and splenic glycoproteins have similar amino acid composition and differed in the content of neutral and amino-sugars as well as sialic acid. The content of the latter residue was relatively higher in the splenic form of the receptor compared to its thymic counterpart, and was inversely correlated with the content of galactosyl residues in both forms of the receptor. The functional significance of PNA-binding glycoproteins during vertebrate evolution is discussed.

Identification and structural characterization of an LYT-2/3 homolog in tunicates.

1. A serologic and structural homolog to murine Lyt-2/3 molecular complex was sought in tunicate hemocytes by using a monoclonal antibody specific to Lyt-2 framework determinants (mAb 53-6.7). 2. This antibody labeled a distinct population of tunicate hemocytes, as determined in indirect immunofluorescence and FACS analysis, and immunoprecipitated disulfide-bonded subunits from hemocytes equivalent to the 38 kDa (alpha), 34 kDa (alpha') and 30 kDa (beta) subunits of murine Lyt-2/3 molecules. 3. As in mice, tunicate alpha- and alpha' -subunits each appeared to bear three N-linked oligosaccharides, one high mannose- and two complex-type glycans and focused as a number of heterogeneous spots on IEF gels. 4. In contrast, beta-subunits of both species were associated with a single N-linked glycan of the complex type and focused as basic components of limited charge heterogeneity. 5. Based on tryptic peptide patterns, alpha and alpha' -subunits, are likely to be structurally similar in both tunicate and mouse complexes. 6. However, CNBr cleavage patterns indicated that the alpha-subunit of both species may differ in the size-location of the intrachain disulfide bridge. 7. Collectively our observations suggest the phylogenetic emergence of an Lyt-2/3 homolog at an early level of evolution.

Identification and structural characterization of Lyt-1 glycoproteins from tunicate hemocytes and mouse thymocytes.

1. A panel of monoclonal antibodies specific to murine Lyt-1 allotypic and framework determinants was used to investigate the possible occurrence of a Lyt-1 homolog in tunicate (protochoradte) hemocytes. 2. In immunoprecipitation experiments, antigenic activities were associated with a major 67 kDa component on tunicate hemocytes and C57Bl/6 mouse thymocytes. 3. Tunicate and mouse Lyt-1 molecules were compared, in terms of glycosylation, by their sensitivity to glycosidases and analyses on one- and two-dimensional gel electrophoresis. 4. Each of the two molecules appeared to bear two N-linked oligosaccharides, one high-mannose and one complex-type glycan. 5. Both molecules revealed charge microheterogeneity with differences in sialic acid content accounting for the charge difference between each other. 6. However, the difference in the glycans did not account for the microheterogeneity within each molecule, suggesting that other post-translational modifications might be responsible. 7. At the polypeptide level, comparisons of chymotryptic and endoproteinase-Arg-C peptide maps, as well as CNBr-cleavage products, suggested that tunicate and mouse Lyt-1 molecules are structurally similar and that each may contain at least one intra-chain disulfide bridge. 8. The significance of these findings is discussed in terms of the possible biological role of Lyt-1 glycoproteins at different levels of evolution.

Serological characterization and partial purification of an Lyt-1 homolog in tunicate hemocytes.

A panel of alloantisera and monoclonal antibodies specific to murine Lyt-1 allotypic and framework determinants was used in indirect immunofluorescence and FACS analysis to investigate the occurrence of an Lyt-1 homolog in tunicate (protochordate) hemocytes. Binding assays and quantitative absorption experiments established the expression of Lyt-1 cross-reacting determinants on a distinct population of tunicate hemocytes. These determinants were expressed exclusively by cells with the morphological characteristics of hemoblasts and lymphocytes. In a rapid two-step purification procedure, Lyt-1 glycoproteins from tunicate hemocytes and C57B1/6 mouse thymocytes were solubilized and partially purified by affinity chromatography using a mAb anti-Lyt-1 frame-work determinant. In both cell types, antigenic activities were associated with a major 67-kDa component. Our findings suggest an early phylogenetic emergence of an Lyt-1 homolog at this level of evolution.

Phylogenesis of lymphocyte diversity. II. Characterization of Agama stellio Ig-negative lymphocytes by a heterologous anti-thymocyte serum.

A specific antiserum was raised in rabbits against thymocytes of the lizard Agama stellio (ATS). In indirect immunofluorescent (IF) assays, the in vitro absorbed ATS was, at any given dilution, reactable with thymocytes greater than peripheral blood lymphocytes (PBL) greater than or equal to splenocytes greater than bone marrow lymphocytes (BML). In quantitative absorption analyses the specificity of ATS for recognizing antigenic determinant(s) specific to Agama thymocytes (ASTA) and shared by other lymphocytes of probable thymic origin was indicated. In view of the inverse correlation of ASTA-bearing lymphocytes with Ig-bearing lymphocytes in lymphoid tissues, and the uniformity of results obtained with either an antiserum raised with Ig-negative thymocytes or antisera absorbed with purified gamma-fractions, ASTA may be a strict phenotype specific to Ig-negative thymocytes and other Ig-negative lymphocytes in the periphery. We propose a dichotomy of the T- and B-like arms of immunity in Agama, on the basis of presence or absence of ASTA.