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The evolutionary development of modifier genes.

The main findings of a study of the evolution of modifier gene frequencies in models of deterministic population genetics are presented. A wide variety of random mating systems are subject to selection with modifiers operating, in different cases, on mutation rates, dominance, migration between subpopulations, and linkage between other loci. In all these instances the modifier frequencies evolve in such a way as to maximize the mean fitness of the population at equilibrium. This is remarkable since, except for the dominance modifier, the modifier genes are selectively neutral in the sense that they do not affect the fitness of their individual carriers. In nonrandom mating systems the mean fitness concept is not well defined, and there does not appear to be such a simple principle governing the evolution of modifier frequencies. In assortative mating systems modifiers favoring reduced assortment propensities tend to increase. In contrast, for selfing-outcrossing systems modifiers favoring increased selfing tend to increase.

Alleles↗

Bifunctional major histocompatibility-linked genetic regulation of cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes.

Murine thymus-derived lymphocytes can be sensitized in vitro to trinitrophenyl (TNP)-modified autologous spleen cells (1, 2). Cytotoxic effector cells were generated which were specific for TNP-modified target cells expressing the same H-2K and H-2D serological regions as the modified stimulator cells (3, 7). Spleen cells from two C57BL/10 congenic strains of mice sharing common I-C, S, and D regions, but differing at K, I-A, and I-B regions, generated different levels of lytic responses to the shared modified H-2Dd products upon sensitization with auto logous TNP-modified cells. Lymphocytes from an F1 between responder and nonresponder strain generated a level of cytolysis toward the H-2Dd modified specificity which was of the same order of magnitude as that obtained with the high responder, irrespective of whether F 1 or either parental strain of modified stimulator cell was used. These results suggest that the modification of H-2Dd products resulted in formation of new antigenic determinants in both parental strains. However, the difference observed in responsiveness appeared to be due to a gene or genes mapping in the K, I-A, or I-B region which influenced the ability of the responding lymphocytes to react to these modified H-2Dd products. Responsiveness was expressed as a dominant trait in the F1.

Alleles↗

Multiple H-2 linked immune response gene control of H-2 D-associated T-cell-mediated lympholysis to trinitrophenyl-modified autologous cells: Ir-like genes mapping to the left of I-A and within the I region.

One of the more recent associations of the murine H-2 major histocompatibility complex (MHC) with immune function has been the finding that cytotoxic T-effector cells generated by sensitization with viral-infected (1-6), chemically modified (7-9), or weak transplantation antigen-associated (10,11) syngeneic cells can efficiently lyse target cells which express the same viral, chemical, or weak antigenic agent, and which share the H-2K and/or H-2D regions of the MHC with the responding and/or stimulating cells. Furthermore, an additional contribution of a gene(s) within the H-2 complex has been demonstrated which controls immune response potential (Ir genes) in the generation of cytotoxic effector cells to trinitrophenyl (TNP)-modified self components (12,13). In such studies it was found that certain B10 congenic strains generated good cytotoxic responses to both TNP- modified H-2K and H-2D region products, whereas other B10 congenic strains exhibited preferential or exclusive reactivity against TNP-modified H-2K region products. Some of these recombinant strains differing in response potential to TNP- modified H-2D products expressed the same haplotype at the D end, but differed at the K end of H-2. The low responsiveness observed in the B10.A strain to TNP-modified H-2D(d) when compared to B10.D2 and (B10.A x B10.D2)F(1) for the same specificity, suggested a role of dominant Ir genes which map in K, I-A, I-B, I-J, and/or I-E (12, 14). In the present report an attemnpt was made to further map within the MHC the Ir gene(s) controlling cell-mediated lympholysis (CML) to TNP-modified H-2D(d), by using recombinant mouse strains on the A and B10 backgrounds. Irrespective of the genetic background, the s and k haplotypes at the K end generated high and low cytotoxic responses, respectively, to H-2D(d)-TNP. The intermediate responder and low responder status of the A.TL and A.AL strains, respectively, indicated that a gene mapping in the K region of H-2 influences response potential. Furthermore, the differences in the levels of cytotoxicity detected in the A.TH and A.TL strains suggested an additional I region influence. Taken together these findings raise the possibility that multiple genes mapping within different regions of the MHC control the level of T-cell-mediated cytotoxicity to chemically modified autologous cells.

Animals↗

Binding of benzocaine in batrachotoxin-modified Na+ channels. State-dependent interactions.

Hille (1977. Journal of General Physiology. 69:497-515) first proposed a modulated receptor hypothesis (MRH) to explain the action of benzocaine in voltage-gated Na+ channels. Using the MRH as a framework, we examined benzocaine binding in batrachotoxin (BTX)-modified Na+ channels under voltage-clamp conditions using either step or ramp command signals. We found that benzocaine binding is strongly voltage dependent. At -70 mV, the concentration of benzocaine that inhibits 50% of BTX-modified Na+ currents in GH3 cells (IC50) is 0.2 mM, whereas at +50 mV, the IC50 is 1.3 mM. Dose-response curves indicate that only one molecule of benzocaine is required to bind with one BTX-modified Na+ channel at -70 mV, whereas approximately two molecules are needed at +50 mV. Upon treatment with the inactivation modifier chloramine-T, the binding affinity of benzocaine is reduced significantly at -70 mV, probably as a result of the removal of the inactivated state of BTX-modified Na+ channels. The same treatment, however, enhances the binding affinity of cocaine near this voltage. External Na+ ions appear to have little effect on benzocaine binding, although they do affect cocaine binding. We conclude that two mechanisms underlie the action of local anesthetics in BTX-modified Na+ channels. Unlike open-channel blockers such as cocaine and bupivacaine, neutral benzocaine binds preferentially with BTX-modified Na+ channels in a closed state. Furthermore, benzocaine can be modified chemically so that it behaves like an open-channel blocker. This compound also elicits a use-dependent block in unmodified Na+ channels after repetitive depolarizations, whereas benzocaine does not. The implications of these findings for the MRH theory will be discussed.

Animals↗

The binding efficiency of polyclonal and monoclonal antibodies to DNA modified with benzo[a]pyrene diol epoxide is dependent on the level of modification. Implications for quantitation of benzo[a]pyrene-DNA adducts in vivo.

A number of polyclonal antibodies specific for DNA modified with (+/-)trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyre ne (BPDE) were obtained from the sera of New Zealand white rabbits immunized with BPDE-DNA, complexed with methylated bovine serum albumin (mBSA). Monoclonal antibodies were developed by fusion of mouse myeloma cells with spleen cells isolated from BALB/c mice immunized with the same complex of BPDE-DNA and mBSA. These antibodies have been characterized for specificity in a highly sensitive, enzyme-linked immunosorbent assay (ELISA). All antibodies showed a very high affinity for single-stranded BPDE-DNA, but had lower affinity towards native BPDE-DNA. The affinity for the free mononucleoside BPDE-dG was at least 100-fold lower than that for BPDE-DNA, and no affinity was detected for BP tetrols or DNA modified with N-acetoxy-N-acetyl-2-aminofluorene. A high cross reactivity was observed with DNA modified with (+/-)-trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydrochrysene++ +. Using five different antibodies, monoclonal or polyclonal, we observed that the antibody affinity for BPDE-DNA was dependent on the level of modification; in the competitive ELISA as little as 4 fmol BPDE-DNA (50 pmol/micrograms) was sufficient for 50% inhibition with our best antisera, but 17 fmol of the adduct was required when [3H]BPDE-DNA of low modification (1-10 fmol/micrograms) was used as inhibitor. When samples of [3H]BP-DNA isolated from the livers of mice, treated i.p. with different doses of [3H]BP were examined by competitive ELISA and calibrated with [3H]BPDE-DNA of low modification (1-10 fmol/micrograms), binding values calculated from the immunoassay were in good agreement with those obtained from radioactivity measurements. In contrast, when this DNA was quantitated in competitive ELISA using highly modified BPDE-DNA as standards, values by ELISA were 20-40% of those obtained by radioactivity. These results indicate that the use of serially diluted BPDE-DNA of high modification as standard competitor in the ELISA will lead to erroneous results in the measurement of adducts in DNAs modified to a low extent (biological samples). The property of antisera specific for BP-DNA, recognizing highly modified DNA more efficiently than DNA modified to a low extent, may be common to all antisera elicited against highly modified DNA immunogens. Therefore we conclude that antibody affinity must be tested also with DNA samples of low modification, obtained either in vitro or in vivo.

2-Acetylaminofluorene↗

Comparative analysis of position-effect variegation mutations in Drosophila melanogaster delineates the targets of modifiers.

In Drosophila melanogaster, heterochromatin-induced silencing or position-effect variegation (PEV) of a reporter gene has provided insights into the properties of heterochromatin. Class I modifiers suppress PEV, and class II modifiers enhance PEV when the modifier gene is present in fewer than two doses. We have examined the effects of both class I and class II modifiers on four PEV mutations. These mutations include the inversions In(1)w(m4) and In(2R)bw(VDe2), which are classical chromosomal rearrangements that typify PEV mutations. The other mutations are a derivative of brown(Dominant), in which brown+ reporters are inactivated by a large block of heterochromatin, and a P[white+] transposon insertion associated with second chromosome heterochromatin. In general, we find that class I modifiers affect both classical and nonclassical PEV mutations, whereas class II modifiers affect only classical PEV mutations. We suggest that class II modifiers affect chromatin architecture in the vicinity of reporter genes, and only class I modifiers identify proteins that are potentially involved in heterochromatin formation or maintenance. In addition, our observations support a model in which there are different constraints on the process of heterochromatin-induced silencing in classical vs. nonclassical PEV mutations.

Animals↗

Comparison of 99mTc-DTPA renal dynamic imaging with modified MDRD equation for glomerular filtration rate estimation in Chinese patients in different stages of chronic kidney disease.

BACKGROUND: The renal dynamic imaging method (modified Gate's method) with (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) is simple and less time consuming for glomerular filtration rate (GFR) estimation than other methods. However, its diagnostic performance as a surrogate marker of GFR is questioned increasingly. Recently, the modified Modification of Diet in Renal Disease (MDRD) study equation based on data from Chinese patients of chronic kidney disease (CKD) showed significant performance improvement. In the present study, the renal dynamic imaging methods and the modified abbreviated MDRD equation were compared with the plasma clearance method. METHODS: Four hundred and eighty two patients with CKD were selected. GFR were estimated simultaneously using three methods: (i) modified Gate's method (gGFR); (ii) the modified abbreviated MDRD equation (c-aGFR) and (iii) dual plasma sampling method (rGFR). Using rGFR as the reference method, gGFR and c-aGFR were compared with rGFR in each stage of CKD. RESULTS: Both gGFR and c-aGFR were correlated well with rGFR (r(gGFR) = 0.81 and r(c-aGFR) = 0.90, P < 0.001). In the overall performance, c-aGFR had less bias (849.5 vs 933.1 arbitrary units), higher precision (57 vs 78.4 ml/min/1.73 m(2)) and higher accuracy than gGFR. For gGFR, the 15, 30 and 50% accuracies were 32.4, 56.0 and 79.1%, respectively; for c-aGFR, the corresponding accuracy rose to 43.2%, 75.5% and 90.9%, respectively. In each stage of CKD, the modified abbreviated MDRD equation also outperformed the modified Gate's method in the GFR estimation. CONCLUSION: Our results indicated that the performance of the renal dynamic imaging in total GFR estimation was not better than the modified abbreviated MDRD equation in our patient group, and should not be used as a surrogate marker of GFR, especially in clinical trials. We presume that the dynamic renal imaging methods for estimation of GFR can be improved by using proper reference GFR, more adequate background subtraction and soft-tissue attenuation correction, in a relatively larger sample size.

Asian People↗

Modulation of stability properties of bovine trypsin after in vitro structural changes with a variety of chemical modifiers.

Controlled chemical modification of enzymes, targeting groups not involved in the active site, can lead to modified catalysts that are intrinsically more efficient and resistant to heat and denaturing agents. Bovine pancreatic trypsin was covalently modified up to 75-85% with monomeric glutaraldehyde (MGA), polymeric glutaraldehyde (PGA), oxidized sucrose and oxidized sucrose polymers (OSP 70 and OSP 400). Virtually no loss in activity occurred upon modification. Temperature optima of trypsin shifts from 45-76 degrees C and T50 from 54-76 degrees C for the best modified sample made with OSP. The efficiency of the modifiers in stabilization was ranked in the order: OSP 400-T > OSP 70-T > PGA-T > MGA-T > Sucrose-T. Half-life of modified enzymes also followed the same trend. Both stabilization factor and t1/2 decreased with increasing temperatures. The free energy of activation for inactivation delta(deltaG*) varies from 12-20 kJ/mol and the activation enthalpy delta(deltaH*) of the modified trypsin by 80-120 kJ/mol indicating stabilization. Inactivation of modified trypsin by urea is less noticeable. The character of the two-step inactivation process of trypsin changes with the degree of stabilization in that the duration of phase I one increased noticeably as stabilization increases. Native trypsin fluoresces less intensely showing a red shift under the influence of denaturation. Such a fluorescence change is not so obvious for the modified enzymes indicating conformational stability acquired by modification.

Animals↗

Long-term followup of penile carcinoma treated with penectomy and bilateral modified inguinal lymphadenectomy.

PURPOSE: We evaluated modified inguinal lymphadenectomy in the treatment of penile carcinoma, analyzing the rate of complications compared to complete inguinal lymphadenectomy, the complications in performing lymphadenectomy and penectomy concomitantly, and the long-term locoregional recurrence rate. MATERIALS AND METHODS: A total of 26 patients with squamous cell carcinoma of the penis were clinically assessed, and underwent penectomy and bilateral modified inguinal lymphadenectomy at the same operative time. Frozen section analysis of lymph nodes was performed and if metastases were detected a complete ipsilateral inguinal dissection was performed. RESULTS: A total of 52 modified lymphadenectomies were performed. In 10 procedures lymph node metastasis was present. Clinical staging presented false-positive and false-negative rates of 50% and 7.9%, respectively. The complication rate for modified lymphadenectomy was 38.9% and for complete inguinal lymphadenectomy it was 87.5%. Followup ranged from 5 to 112 months and mean followup of recurrence-free cases was 78 months (range 38 to 112). A total of 18 patients underwent bilateral negative modified inguinal lymphadenectomy and 2 of these experienced locoregional recurrence within 2 years after surgery. CONCLUSIONS: Modified inguinal lymphadenectomy causes a lower complication rate than complete inguinal lymphadenectomy. Bilateral modified inguinal lymphadenectomy performed at the same time as penectomy does not increase the complication rate. When frozen section analysis is negative bilaterally, 5.5% of inguinal regions might still harbor occult metastasis. Modified inguinal lymphadenectomy is recommended as a staging procedure in all patients with T2-3 penile carcinoma. A straight followup is required for 2 years since all recurrence was within this period.

Adult↗

Polysaccharide-degrading Enzymes are Unable to Attack Plant Cell Walls without Prior Action by a "Wall-modifying Enzyme".

A study of the degradation of plant cell walls by the mixture of enzymes present in Pectinol R-10 is described. A "wall-modifying enzyme" has been purified from this mixture by a combination of diethylaminoethyl cellulose, Bio Gel P-100, and carboxymethyl cellulose chromatography. Treatment of cell walls with the "wall-modifying enzyme" is shown to be a necessary prerequisite to wall degradation catalyzed by a mixture of polysaccharide-degrading enzymes prepared from Pectinol R-10 or by an alpha-galactosidase secreted by the pathogenic fungus Colletotrichum lindemuthianum. The action of the "wall-modifying enzyme" on cell walls is shown to result in both a release of water-soluble, 70% ethanol-insoluble polymers and an alteration of the residual cell wall. A purified preparation of the "wall-modifying enzyme" is unable to degrade a wide variety of polysaccharide, glycoside, and peptide substrates. However, the purified preparation of wall-modifying enzyme has a limited ability to degrade polygalacturonic acid. The fact that polygalacturonic acid inhibits the ability of the "wall-modifying enzyme" to affect cell walls suggests that the "wall-modifying enzyme" may be responsible for the limited polygalacturonic acid-degrading activity present in the purified preparation. The importance of a wall-modifying enzyme in developmental processes and in pathogenesis is discussed.

Journal Article↗

opaque-2 modifiers increase gamma-zein synthesis and alter its spatial distribution in maize endosperm.

Through the action of opaque-2 modifier genes, the soft, floury endosperm of opaque-2 mutants is converted to a vitreous phenotype. This change in endosperm texture is associated with a twofold to threefold increase in gamma-zein content. To investigate the effect of opaque-2 modifiers on the expression of gamma-zein genes, we analyzed the synthesis and distribution of gamma-zein protein and the level of gamma-zein mRNAs in developing endosperms of the inbreds W64A and W64Ao2, a modified opaque-2 mutant Pool 34 QPM, and their reciprocal F1 hybrids. We also characterized the number and organization of gamma-zein genes in these and related maize genotypes. Our studies show that opaque-2 modifiers are semidominant genes, resulting in a twofold to threefold increase in gamma-zein gene expression in both opaque-2 and normal genetic backgrounds. The increase in gene expression appears to be a consequence of enhanced mRNA transcription or stability rather than gene amplification because gamma-zein genes occur in one or two copies in modified as well as nonmodified genetic backgrounds. Ultrastructural studies showed that gamma-zein occurs in high concentrations in the first few subaleurone cells of nonmodified endosperms, but high concentrations of gamma-zein occur in the subaleurone and central endosperm cells of modified opaque-2 mutants. The increased concentration and distribution of gamma-zein in modified endosperms are highly correlated with the activity of opaque-2 modifier genes.

Microscopy, Immunoelectron↗

opaque2 modifiers act post-transcriptionally and in a polar manner on gamma-zein gene expression in maize endosperm.

The opaque2 (o2) modifier genes convert the soft endosperm of an o2 mutant to a hard, vitreous phenotype. The primary biochemical change associated with the expression of these genes is a two- to threefold increase in synthesis of the 27-kD gamma-zein storage protein. To investigate the mechanism of modifier gene activity, we examined the level of gamma-zein mRNA and protein synthesis during the early stages of endosperm development in normal, o2, and modified o2 geno-types. Although the o2 mutation was found to reduce expression of the 27-kD gamma-zein genes, the activity of o2 modifier genes dramatically increased the level of both gamma-zein protein and mRNAs as early as 16 days after pollination. At this stage, transcription of gamma-zein genes is reduced by approximately 50% in both o2 and modified o2 genotypes compared to wild type. Thus, it appears that the modifiers regulate gamma-zein synthesis through a post-transcriptional mechanism. Analysis of transcripts from the two nearly identical genes (A and B) encoding the 27-kD gamma-zein protein showed differences in the mRNA ratios in different genotypes. In modified o2 mutants, accumulation of A over B transcript was greatly enhanced during endosperm development. Somatic recombination at this locus was found to reduce the number of B genes in the endosperm, but this could not account for the preferential accumulation of the A transcript. Our results suggest that a product of the o2 modifier genes increases the translation or stability of the A gene mRNA, leading to enhanced synthesis of 27-kD gamma-zein protein.

Base Sequence↗

Genetically modified skin to treat disease: potential and limitations.

Molecular definition of disease at the level of the gene and advances in recombinant DNA technology suggest that many diseases are amenable to correction by genes not bearing the defective elements that result in disease. Many questions must be answered before this therapy can be used to correct chronic diseases. These questions fall into safety and efficacy categories. Experience with transplanting cellular elements of skin or skin substitutes (defined as skin that possess the cell types and a dermal structure to develop into a functioning skin) to athymic rodents is considerable and is seen as a system where these questions can be answered. This paper reviews these questions and presents our early analysis of genetically modified cells in skin substitutes in vivo and in vitro. Experimental data demonstrate that both a matrix of woven nylon, housing a fibroblast generated collage, and dead dermis can be utilized to shuttle genetically modified human fibroblasts from the laboratory to an in vivo setting. Genetically modified fibroblasts do not migrate from the shuttle to the surrounding tissue. The survival of significant numbers, approximately 70%, of genetically modified fibroblasts for at least 6 weeks in these shuttles, supports this general approach as having clinical utility. It is also concluded that skin substitute systems can be used to generate a genetically modified skin in vitro that has the capacity to develop into functional skin in vivo. Further, as genetically modified keratinocytes differentiate there is increased production by the transgene, supporting the concept that keratinocytes have true potential as shuttles for therapeutic genes. This work demonstrates that transplantation of systems containing genetically modified cells of the skin can be used to experimentally define many aspects of gene therapy using skin before this technology is taken to the clinic. Examples include determining the effect of gene transduction and expression on structure and function of the genetically modified skin as well as on distant skin and an assessment of the translational capacity of the transgene as function of time and cell number.

3T3 Cells↗

Modified formulation of CPDA for storage of whole blood, and of SAGM for storage of red blood cells, to maintain the concentration of 2,3-diphosphoglycerate.

BACKGROUND AND OBJECTIVES: A dramatic decrease in the level of 2,3-diphosphoglycerate (2,3-DPG) takes place during the storage of whole blood (WB) in CPDA (citrate-phosphate-dextrose-adenine) and a similar decrease occurs during the storage of red blood cells (RBCs) in SAGM (saline-adenine-glucose-mannitol). The aim of the present study was to prevent this decrease by modifying CPDA and SAGM. MATERIALS AND METHODS: The pH of WB anticoagulant or RBC preservative solution was maintained at 7.6 by autoclaving the dextrose solution separately, by incorporating ascorbic acid and nicotinic acid into both CPDA and SAGM (to produce modified CPDA and SAGM solutions), and by reducing the concentration of adenine and adding citrate to the modified SAGM solution. The concentration of 2,3-DPG in WB after 28 days of storage in modified CPDA, and in RBCs stored in modified SAGM, was compared with that in WB or RBCs stored in unmodified solutions. RESULTS: The initial 2,3-DPG levels were maintained after 28 days in the modified formulations [10.63 +/- 2.58 microM/g of haemoglobin (Hb) in the case of modified CPDA and 12.07 +/- 1.47 microM/g of Hb in the case of modified SAGM], whereas in standard CPDA and SAGM solutions, the concentration of 2,3-DPG decreased to very low levels (0.86 +/- 0.97 microM/g Hb for CPDA and 0.12 +/- 0.008 for SAGM). CONCLUSIONS: Our modification in the formulation of CPDA or SAGM is effective in arresting the dramatic decrease in the level of 2,3-DPG that occurs during storage of WB and RBCs in unmodified solutions.

2,3-Diphosphoglycerate↗

Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides.

Malondialdehyde (MDA), a peroxidative end-product released during polyunsaturated fatty acid degradation, reacts strongly with lysine residues of cellular proteins. MDA-modified proteins become immunogenic and may elicit specific autoantibody formation. We hypothesized that systemic diseases in which inflammatory events occur, could be an interesting model for studying oxidative stress. A few studies have suggested that MDA-modified proteins may exist in systemic diseases, and that autoantibodies to MDA-modified structures might reflect this oxidative process. Autoantibodies to MDA-modified epitope(s) were therefore assayed in sera of patients with systemic lupus erythematosus (SLE, n = 29), scleroderma (SCL, n = 11), giant cell arteritis (GCA, n = 11), periarteritis nodosa (PAN, n = 10), rheumatoid arthritis (RA, n = 9), and healthy subjects (HS, n = 32). Significantly increased anti-MDA-modified epitope(s) autoantibodies were found in patients with SLE and also in other systemic diseases such as PAN and SCL. Autoantibodies to MDA-modified epitope(s) were predominantly of IgM isotype, with low levels of IgG and no IgA activity. In SLE, anti-MDA-modified epitope(s) autoantibody titres correlated strongly with systemic lupus activity measure (SLAM, r = 0.702, P = 0.0001), anti-nuclear antigen autoantibodies (ANA, r = 0.4, P = 0.029), IgG anti-cardiolipin (r = 0.558, P = 0.03) and the steroid drug regimen (r = 0.52, P = 0.004). Autoantibodies to MDA-modified epitope(s) may reflect oxidative modifications occurring in systemic diseases, and might be useful as clinical markers of SLE activity if further investigated.

Adult↗

Comparison of energy and protein intakes of older people consuming a texture modified diet with a normal hospital diet.

BACKGROUND: There are very few studies looking at the energy and protein requirements of patients requiring texture modified diets. Dysphagia is the main indication for people to be recommended texture-modified diets. Older people post-stroke are the key group in the hospital setting who consume this type of diet. The diets can be of several consistencies ranging from pureed to soft textures. OBJECTIVE: To compare the 24-hour dietary intake of older people consuming a texture modified diet in a clinical setting to older people consuming a normal hospital diet. METHOD: Weighed food intakes and food record charts were used to quantify the patients' intakes, which were compared to their individual requirements. RESULTS: The oral intake of 55 patients was measured. Twenty-five of the patients surveyed were eating a normal diet and acted as controls for 30 patients who were prescribed a texture-modified diet. The results showed that the texture-modified group had significantly lower intakes of energy (3877 versus 6115 kJ, P < 0.0001) and protein (40 versus 60 g, P < 0.003) compared to consumption of the normal diet. The energy and protein deficit from estimated requirements was significantly greater in the texture-modified group (2549 versus 357 kJ, P < 0.0001; 6 versus 22 g, P = 0.013; respectively). CONCLUSION: These statistically significant results indicate that older people on texture-modified diets have a lower intake of energy and protein than those consuming a normal hospital diet and it is likely that other nutrients will be inadequate. All patients on texture-modified diets should be assessed by the dietitian for nutritional support. Evidence based strategies for improving overall nutrient intake should be identified.

Aged↗

Tensile bond strength of resin-modified glass-ionomer cement to microabraded and silica-coated or tin-plated high noble ceramic alloy.

PURPOSE: The purpose of this study was to evaluate the influence of alloy surface microabrasion, silica coating, or microabrasion plus tin plating on the tensile bond strengths between a resin-modified glass-ionomer luting cement and a high-noble alloy. Bond strength between the microabraded alloy specimens and conventional glass-ionomer cement or resin cement were included for comparison. MATERIALS AND METHODS: One hundred twenty uniform size, disk-shaped specimens were cast in a noble metal alloy and divided into 6 groups (n = 10 pairs/group). The metal surfaces of the specimens in each group were treated and cemented as follows. Group 1: No surface treatment (as cast, control), cemented with a resin-modified glass-ionomer cement. Group 2: Microabrasion with 50-microm aluminum oxide particles, resin-modified glass-ionomer cement. Group 3: A laboratory microabrasion and silica coating system, resin-modified glass-ionomer cement. Group 4: Microabrasion and tin-plating, resin-modified glass-ionomer cement. Group 5: Microabrasion only, conventional glass-ionomer cement. Group 6: Microabrasion and tin-plating, conventional resin cement. The uniaxial tensile bond strength for each specimen pair was determined using an Instron Universal Testing Machine (Instron Corp, Canton, MA). Results were analyzed using a one-way analysis of variance (alpha = 0.05) and a Tukey post-hoc analysis. RESULTS: Mean bond strength: Group 1: 3.6 (+/- 1.5) MPa. Group 2: 4.2 (+/-0.5) MPa. Group 3: 6.7 (+/- 0.9) MPa. Group 4: 10.6 (+/- 1.8) MPa. Group 5: 1.1 (+/- 0.4) MPa. Group 6: 14.6 (+/- 2.3) MPa. Group 6 was significantly stronger than Group 4. The bond strength of specimens cemented with the resin-modified glass-ionomer cement using microabrasion and tin-plating (Group 4) was significantly stronger than all other groups except the resin cement with microabrasion and tin-plating (Group 6). CONCLUSION: Microabraded and tin-plated alloy specimens luted with the resin-modified glass-ionomer cement resulted in the greatest mean tensile strengths for the resin-modified glass-ionomer cement groups. This strength was 73% of the mean tensile strength of microabraded specimens luted with resin cement.

Aluminum Oxide↗

Biodistribution of cyclosporin encapsulated in liposomes modified with bioadhesive polymer.

The purpose of this investigation was to study the possibility of renewing the immunosuppressive activity of cyclosporin by formulating the compound in liposomes modified with bioadhesive polymers. The liposomes prepared were evaluated both pharmacokinetically and pharmacodynamically. Tissue distribution and plasma pharmacokinetics of cyclosporin and model dye, sudan black, which is as hydrophobic as cyclosporin, were studied in rats after intravenous infusion (10 mg kg-1). The immunosuppressive efficacy of liposomal cyclosporin preparations was studied in the allogenic rat-heart-transplantation model, where cyclosporin therapy (10 mg kg-1) continued for one week. The entrapment of sudan black in liposomes modified with bioadhesive polymers resulted in higher sudan black delivery to the spleen and the liver than with standard sudan-black-loaded liposomes. Among the modified liposomes, those modified with carbopol 941 showed the most remarkable enhancing effect on the delivery of sudan black to these organs and total plasma clearance of sudan black decreased to 38.6 +/- 7.8 mL h-1 kg-1 (standard liposomes, 58.9 +/- 6.4 mL h-1 kg-1). Delivery of cyclosporin to the spleen and the liver was increased approximately twofold by modifying the liposomes with carbopol 941. In the preliminary study on the allogenic rat-heart-transplantation model, the mean survival days of the graft were 18.8 +/- 2.9 days for the group receiving cyclosporin liposomes modified with carbopol 941, 14.2 +/- 4.4 days for the group receiving standard cyclosporin liposomes and 7.6 +/- 0.5 days for the group receiving cyclosporin solution. The encapsulation of cyclosporin in liposomes modified with bioadhesive polymer enhanced the residence time of cyclosporin in the systemic circulation, resulting in approximately twofold greater delivery of cyclosporin to the spleen and liver. However, in the allogenic rat-heart-transplantation model no significant difference was detected between the immunosuppressive efficacy of cyclosporin encapsulated in bioadhesive polymer-modified liposomes and that encapsulated in standard liposomes.

Acrylic Resins↗