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Chemically modified papain for applications in detergent formulations.

Papain was modified using succinic anhydride, and the modified papain so obtained was compared with the native papain for its activity and stability in detergents. This study was done using commercial enzyme detergents as references. It was found that modified papain retained activity comparable to the commercial enzyme detergents. Chemically modified papain may prove to be an inexpensive alternative to alkaline proteases that are used in detergents.

Biotechnology↗

Synthesis and properties of oligo-2'-deoxyribonucleotides containing internucleotidic phosphoramidate linkages modified with pendant groups ending with either two amino or two hydroxyl functions.

Single and multiple incorporations of stereochemically pure modified dinucleoside-phosphoramidates involving substituent groups ending with bis-hydroxyethyl and bis-aminoethyl groups have been performed into pyrimidic triple helix-forming oligo-2'-deoxyribonucleotides designed to bind parallel to the purine strand of the DNA target. The ability of these modified oligo-2'-deoxyribonucleotides to form triple helices has been studied by UV-melting curve analyses, and circular dichroism. Only the oligonucleotides involving modified phosphate groups with the Rp configuration formed more stable triple helices than did the parent phosphodiester sequences. Incorporating the modifications into the third oligonucleotide strands has little effect on the structure of the triplexes. At pH 7, the incorporation of two, three or four modified phosphate groups into the third strands stabilizes the triplexes, as compared to the unmodified oligonucleotide. Stronger stabilization was observed with compounds containing linkers ending with amino functions. Stability increases with the number of modifications without being fully additive. This might be due to the different environments of the phosphate groups inside the sequence.

Amides↗

Stability of simultaneous modified LeFort III/LeFort I osteotomies.

The objective of this study was to examine maxillary skeletal stability after simultaneous modified LeFort III/LeFort I osteotomy in patients who presented for the simultaneous correction of midface and maxillary hypoplasia. Eleven patients underwent simultaneous modified LeFort III/LeFort I osteotomies using transoral and transconjunctival surgical approaches. The mean net surgical movement at A point (A pt) was 5.2 mm anteriorly and 2 mm inferiorly. Titanium mini-plates were used to stabilize both the midface component and the LeFort I segment; iliac crest or calvarial bone grafts as well as freeze-dried cancellous blocks were used at the zygoma and lateral orbital rim regions. All patients had lateral cephalometric radiographs taken immediately postoperatively, and at their sixth week, sixth month, and one year follow-up visits. Five maxillary landmarks (CI, A pt, ANS, PNS, and 2M) were used to examine the horizontal and vertical changes occurring at each time period. The central incisor relapsed vertically 2.8 mm at six months, A pt relapsed vertically 2.3 mm at six months, ANS relapsed posteriorly 1.6 mm at 6 weeks, PNS relapsed 1.5 mm anteriorly at one year. This study demonstrated that the maxilla moved anteriorly 1.5 mm and superiorly 2.8 mm in simultaneous modified LeFort III/LeFort I osteotomies performed with mini-plate fixation and bone grafts. This movement should be considered when planning and performing simultaneous surgical movement of the maxilla and midface using modified LeFort II/LeFort I osteotomies. Appropriate occlusal overcorrection at the time of surgery is necessary.

Adolescent↗

Influence of combined zero-balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass grafting.

OBJECTIVE: To evaluate whether combined zero-balanced and modified ultrafiltration affects the systemic inflammatory response in coronary artery bypass graft (CABG) patients. DESIGN: Randomized and controlled. SETTING: University-affiliated heart center. PARTICIPANTS: Forty-three patients scheduled for elective CABG. INTERVENTIONS: In the ultrafiltration group (UF group; n = 21), zero-balanced ultrafiltration was performed during rewarming and modified ultrafiltration immediately after the end of cardiopulmonary bypass (CPB). A control group of patients (n = 22) was treated identically to the treatment group except no ultrafiltration process was performed. MEASUREMENTS AND MAIN RESULTS: Immediately after CPB (ie, after zero-balanced ultrafiltration), and again after the modified ultrafiltration, the concentrations of interleukin-6 and interleukin-8 were significantly less (p < 0.05) in the UF group compared with the control group. Both proinflammatory cytokine levels peaked at 2 and 4 hours after CPB, at which time no difference between the two groups could be observed. The levels of measured anti-inflammatory mediators (interleukin-10 and interleukin-1 receptor antagonist) did not show any difference between the two groups. Intrapulmonary shunt fraction decreased in the course of the modified ultrafiltration from 31% +/- 1.2% to 25% +/- 1.3% (p < 0.01), whereas mean arterial pressure increased (69 +/- 1.8 to 80 +/- 2.8 mmHg; p < 0.01); neither parameter changed in the control group. Time to extubation was shorter in the UF group (6.1 +/- 0.5 v 8.6 +/- 0.7 hours; p < 0.05). CONCLUSION: It was concluded that the use of ultrafiltration diminished inflammatory response in a very limited time period immediately after CPB and, probably as a consequence, slightly improved clinical parameters.

Blood Pressure↗

Critical evaluation of the modified Lapidus procedure.

The modified Lapidus procedure has been used for treatment of hallux abducto valgus for many years, yet only a handful of reports evaluate procedure outcome. The purpose of this investigation was twofold: 1) to provide a retrospective outcome analysis of the modified Lapidus procedure using subjective and objective criteria, and 2) to evaluate procedure outcome in patient populations with differing functional demands: athletes, active patients, and sedentary patients. Thirty-four patients (42 feet) had the modified Lapidus procedure performed by the senior author (R.T.B.) over a 7-year period. Nine patients were lost to follow-up leaving 25 patients (32 feet) for study inclusion. Twenty-three females and two males with average age 44.4 years (range 15-71 years) were evaluated at an average follow-up time of 39 months (range 13-91 months). Evaluation consisted of subjective questionnaire, physical examination, and radiographic assessment. Subjective evaluation revealed that 78% of patients rated surgery "completely" or "very" effective. Athletes demonstrated lower return to preoperative activity levels (30%) than did active patients (86%) and sedentary patients (75%), but this was not statistically significant. Seventy-seven percent of athletes rated surgery "completely" or "very" effective. Postoperative intermetatarsal angle averaged 8.2 degrees (range -2 to 15) and first metatarsophalangeal joint dorsiflexion averaged 62.6 degrees (range 20- 90 degrees). Intermetatarsal angle correction to 10 degrees or less and postoperative first metatarso-phalangeal joint dorsiflexion 45 degrees or greater correlated with improved subjective results. The modified Lapidus procedure is an effective procedure in patients with hypermobility of the first metatarsocuneiform joint. Success is dependent on patient selection, meticulous surgical technique and comprehensive postoperative management.

Adolescent↗

Maximizing radiotracer delivery to experimental atherosclerotic lesions with high-dose, negative charge-modified Z2D3 antibody for immunoscintigraphic targeting.

BACKGROUND: Two factors that directly affect target/background ratio in immunoscintigraphy are the concentration of the antibody bound to the target and the concentration of the antibody in the circulation. High dosages of monoclonal antibody have been reported to be more efficacious in visualization of tumors. Although administration of a higher dosage of antibody increases the absolute target accumulation of the radiotracer, it also increases the background activity, which may offset this advantage. Negative charge-modified antibodies carry high specific radioactivity to the target sites without significantly increasing the background activity. Therefore we investigated whether higher dosages of negative charge-modified antibody can be used to improve imaging of experimental atherosclerotic lesions. METHODS AND RESULTS: Experimental atherosclerotic lesions were produced in 16 New Zealand White rabbits by balloon deendothelialization of the infradiaphragmatic aorta and hyperlipidemic diet for 12 weeks. Negative charge-modified Z2D3 antibody F(ab')2 specific for an antigen on proliferating smooth muscle cells of human atheroma labeled with (111)In was used for imaging experimental atherosclerotic lesions either at high (100 to 125 microg) or low (25 to 50 microg) dosages. A lower dosage of Z2D3 was labeled with 507 +/- 29.5 microCi (25 to 50 microg) (111)In label, compared with 2.9 +/- 0.24 mCi (100 to 125 microg) for the higher dosage. Although noninvasive visualization of atherosclerotic lesions was possible in all animals at 24 hours, high antibody dose allowed unequivocal visualization of the lesion as early as 3 hours after intravenous administration of the antibody. Eight animals were killed at 24 hours and the remaining eight animals at 48 hours. Mean radioactivity dose delivered per gram of lesion with the low-dose protocol at 24 hours was 0.46 +/- 0.09 microCi, which remained essentially unchanged at 48 hours (0.37 +/- 0.09 microCi; p = 0.51). With the high-dosage protocol, the total radioactivity (dose) per gram uptake in the lesion increased by about eightfold (3.49 +/- 0.58 microCi; p = 0.002) at 24 hours and was sixfold higher at 48 hours (2.21 +/- 0.45 microCi; p < 0.02). CONCLUSIONS: The study demonstrated that the increase in the dosage of negatively charge-modified antibody allows a very high delivery of specific radioactivity to the target, which in turn enables early visualization of experimental atherosclerotic lesions.

Animals↗

Long-term follow-up of modified condylotomy for internal derangement of the temporomandibular joint.

OBJECTIVES: The purpose of this study was to evaluate disk position and patient response 10 years after modified condylotomy for symptomatic reducing disk displacement. STUDY DESIGNS: Questionnaires and invitations to return for examination and temporomandibular joint magnetic resonance imaging were mailed to 39 consecutive patients 10 years after modified condylotomy. RESULTS: On a 10-point scale the mean pain experienced by the 17 respondents (27 joints) to the questionnaire was 2.0. Ninety percent of 20 joints (12 patients) examined were free of tenderness to palpation. Magnetic resonance imaging in 10 patients (17 joints) showed disk reduction in 59%, displacement with reduction in 29%, and displacement without reduction in 12%. Eighty-five percent of the joints met American Association of Oral and Maxillofacial surgeons criteria for a successful therapeutic outcome. CONCLUSIONS: The study suggests a role for modified condylotomy in the long-term management of symptoms associated with reducing disk displacement. Further, modified condylotomy can frequently reverse an internal derangement and seems to protect against the natural progression of osteoarthrosis.

Adult↗

Pulp reaction to a tri-cure resin-modified glass ionomer.

OBJECTIVE: This study evaluated the pulp response to a tri-cure resin-modified glass ionomer cement and compared this response to those elicited by a zinc oxide-eugenol cement and a silicate cement. Materials were placed in nonexposed class V cavity preparations on human teeth. STUDY DESIGN: Sixty premolars were selected in orthodontic patients in a voluntary group of teenagers. All cavities were prepared according to International Dental Federation specifications. Resin-modified glass ionomer and silicate applications were carried out according to the manufacturers' instructions. RESULT: All teeth were asymptomatic. Pulp responses to the resin-modified glass ionomer cement were slightly greater than to the zinc-oxide-eugenol cement. Bacterial staining attempts were inconclusive with regard to time intervals and pulp responses. No necrotic pulps were seen in any teeth. CONCLUSION: The tri-cure resin-modified glass ionomer cement elicited a slightly greater adverse pulp response than did the zinc-oxide-eugenol cement with respect to the healing process of the pulp.

Composite Resins↗

Localization of concealed norplant implants and implant fragments by a modified mammography technique.

A modified mammography technique for localization of concealed Norplant implants and Norplant fragments was applied to four patients, ages 18, 35, 22, and 25. A dedicated mammography unit and mammography film screen system affording high resolution and high contrast was applied under the same conditions to each patient. 26 kilovoltage peak (KVp) was used, ranging from 60 to 150 milliamperes. Using both the automatic exposure control and manual techniques, specific milliampere range depended on the specific case. The technique proved successful, as concealed Norplant capsules were exquisitely visualized by films obtained with a Siemens Mammomat 3000. Applying the same modified technique, precise location of the Norplant implants was determined using a fenestrated compression plate with an alphanumeric grid in a manner similar to hookwire localization of breast lesions under mammographic guidance. The capsules were then safely retrieved. We conclude that this modified technique may provide practitioners with valuable assistance in the exact localization of the Norplant capsule(s) or fragments, thereby facilitating their removal. Application of a modified mammography technique reveals precise localization of concealed Norplant capsules facilitating their removal.

Adolescent↗

Structure-modifying agents for osteoarthritis: an update.

The terms "chondroprotective" and "structure-modifying" were coined to identify a class of drugs capable of preventing, stabilizing, or repairing joint damage caused by osteoarthritis. The method of reference for evaluating structure-modifying effects in knee or hip osteoarthritis is the measurement of joint space loss on serial plain radiographs. Joint space width can be measured manually or by a computer. Several radiological techniques have been described for measuring joint space width in the medial femorotibial compartment of the knee and the superolateral part of the hip. Most studies of potentially structure-modifying effects evaluated slow-acting drugs for osteoarthritis, which are currently used for their delayed symptomatic effect in osteoarthritis. Although most of these agents have shown promising effects in vitro, none has been proven to produce clinically meaningful structure-modifying effects in humans with osteoarthritis.

Animals↗

Origins of the aminoglycoside modifying enzymes.

The aminoglycosides represent an important class of antibiotics for the treatment of bacterial infections. Interaction of the aminoglycosides with the bacterial ribosome inhibits protein synthesis, which is their primary mode of action. However, in gram negative bacteria, the ability of aminoglycosides to perturb the cell envelope is also an important mode of action. A common mechanism for aminoglycoside resistance involves modifying enzymes which acetylate, phosphorylate or adenylylate the aminoglycoside. There exists a staggering number of aminoglycoside modifying enzymes in clinical isolates of bacteria. This diversity suggests multiple origins for the present day enzymes. In this review, the possible origins of these modifying enzymes will be presented. Previous proposals describing the origins of these enzymes will be reviewed and potential mechanisms for the development of new aminoglycoside modifying enzymes will be discussed.

Journal Article↗

Effects of N-acetylation degree on N-acetylated chitosan hydrolysis with commercially available and modified pectinases.

Three types of N-acetylated chitosans (NACs) with different degrees of acetylation (DA) were prepared and used as a substrate for enzymatic hydrolysis with a commercially available pectinase and a modified one. Pectinase modification was conducted using polyalkyleneoxide-maleic anhydride copolymer (PEO-MA copolymer). The effects of DA on enzymatic reaction with native and modified pectinases were investigated experimentally. Initial hydrolysis rate and Michaelis-Menten kinetic parameters were measured by analysis of reducing sugars. DA of NAC strongly affected the hydrolytic characteristics of native and modified pectinases. N-acetylation of chitosan increased the initial hydrolysis rate and the enzyme-substrate affinity with respect to both pectinases: NACs with DA over 0.3 showed high initial hydrolysis rate and strong affinity between enzyme and substrate. Especially, when NAC with DA over 0.3 was treated with modified pectinase, the affinity became much stronger than the native pectinase.

Journal Article↗

Evidence of modified LDL in the plasma of hypercholesterolemic WHHL rabbits injected with aqueous extracts of cigarette smoke.

Cigarette smoking is a major risk factor for atherosclerosis, and oxidative modification of low density lipoprotein (LDL) is a key event in the development of atherosclerosis. The aim of the present study was to determine whether modified LDL would be formed in the plasma of Watanabe heritable hyperlipidemic (WHHL) rabbits injected with nicotine-free cigarette smoke extracts (CSE). In order to assess this, cigarette smoke-modified LDL (CS-LDL) was prepared by incubation of rabbit native LDL (N-LDL) with CSE for 24 h. The oxidative modification in CS-LDL was well established by the reduced ratio between two LDL subfractions (LDL2/LDL3) separated by anion-exchange HPLC, together with the fast migration in the anodic direction in agarose gel electrophoresis and the increased lipid peroxide levels. Very similar modification was noted with mildly oxidatively modified LDL prepared by incubation of N-LDL with 5 µM CuCl(2) for 1 h. When WHHL rabbits (n=4) intravenously received a single injection of CSE, the ratio of LDL2/LDL3 was markedly reduced compared with the control rabbits (n=4) while total cholesterol levels in the plasma gradually decreased until 24 h after the injection. These results suggest that oxidatively modified LDL, probably like CS-LDL, is produced in the plasma of WHHL rabbits injected with CSE.

Journal Article↗

Reaction of metallotetraphenylporphyrins on hydroxyl-modified silver colloid and Ag2O colloid by surface-enhanced Raman scattering.

This paper reports a novel reaction of metallotetraphenylporphyrins on hydroxyl-modified silver colloid and Ag2O colloid. Surface-enhanced Raman spectra of Ag(II) and Cu(II) complexes of tetraphenylporphyrin (TPP) adsorbed on the hydroxyl-modified Ag colloid and Ag2O colloid have been studied. The time-dependent SERS spectra of MTPP (M = Ag, Cu) on hydroxyl-modified Ag colloid were recorded and dramatic change on SERS spectra was observed. The final spectra were found to be strikingly different from the corresponding normal Raman spectra (NRS), with the appearance of new Raman bands at 1614. 1417, 947, 674 and 292 cm(-1). The UV-visible absorption spectrum of MTPP on hydroxyl-modified Ag colloid exhibits a broad shoulder near 460 nm. Similar spectral phenomena were also observed for AgTPP and CuTPP adsorbed on Ag2O colloid. The observed spectral alterations were ascribed to new species formation due to the irreducible oxidation of MTPP on the colloids.

Colloids↗

Fully automated DNA extraction from blood using magnetic particles modified with a hyperbranched polyamidoamine dendrimer.

Bacterial and artificial magnetic particles were modified using a polyamidoamine (PAMAM) dendrimer and outer shell amines determined. Bacterial magnetic particles were the most consistently modified. Transmission electron microscopic (TEM) analysis showed that the artificial magnetic particles were structurally damaged by the modification process including sonication. Furthermore, laser particle analysis of the magnetite also revealed damage. Small quantities of dendrimer-modified bacterial magnetic particles were used to extract DNA from blood. The efficiency of DNA recovery was consistently about 30 ng of DNA using 2-10 microg of dendrimer-modified bacterial magnetite. This technique was fully automated using newly developed liquid handling robots and bacterial magnetic particles.

Journal Article↗

Could disease-modifying HIV vaccines cause population-level perversity?

Most current candidate HIV vaccines seem to produce little protection against infection, but reduce viral load and slow the decline in CD4 lymphocyte numbers. Such disease-modifying vaccines could potentially provide important population-level benefits by reducing transmission, but could possibly also increase transmission. We address the following question: could disease-modifying HIV vaccines cause population-level perversity (ie, increase epidemic severity)? By analysing a mathematical model and defining a new quantity-the fitness ratio-we show that disease-modifying vaccines that provide only a low degree of protection against infection and/or generate high fitness ratios will have a high probability of making the epidemic worse. However, we show that if disease-modifying vaccines cause a 1.5 log(10) reduction in viral load (or greater) then perversity cannot occur (assuming risk behaviour does not increase). Finally, we determine threshold surfaces for risk behaviour change that determine the boundary between beneficial and perverse outcomes; the threshold surfaces are determined by the fitness ratio, the proportion of the population that are "successfully vaccinated", and the degree of change of risk behaviour in unvaccinated infected individuals. We discuss the implications of our results for designing optimal vaccination control strategies.

AIDS Vaccines↗

Sequential-injection stripping analysis of nifuroxime using DNA-modified glassy carbon electrodes.

The voltammetric behavior of nifuroxime was investigated comparing stationary voltammetric methods with the recently proposed sequential-injection stripping analysis (SISA), by using cyclic voltammetry (CV) and differential-pulse voltammetry at bare and DNA-modified glassy carbon (GC) electrodes. In cyclic voltammetry, reduction of nifuroxime at DNA-modified electrodes gives rise to a well-defined peak, and in contrast to bare GC surfaces, a re-oxidation peak could be observed. Optimization of the pre-concentration process at the DNA-modified surface led to a significant enhancement of the voltammetric current response, a better defined peak shape and an improved dynamic range. Based on this optimized voltammetric procedure, SISA has been evaluated for the determination of nifuroxime. The flow-system significantly facilitates the regeneration of the DNA-modified electrode surface, hence diminishing problems related to accumulation and memory effects. The linear detection range could be extended to 65 microM with a detection limit (3 s) of 0.68 microM, which corresponds to an absolute amount of 21 ng nifuroxime.

Biosensing Techniques↗

Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line.

We investigated the effects of chemically modified tetracyclines (CMTs) on the production of nitric oxide (NO) and on the synthesis of some cytokines: tumour necrosis factor alpha (TNF-alpha), interleukin(IL)-10 and IL-12 in lipopolysaccharide (LPS)-treated J774 cell line. Furthermore, we studied the ability of these drugs to modify the viability in LPS-stimulated J774 macrophages. CMTs decreased, in a dose-dependent manner, inducible NO synthase (iNOS) activity and, consequently, nitrite formation in J774 cultures. The CMT-induced decrease in NO production is due to the inhibition of enzyme activity rather than to a direct effect on enzyme expression. The absence of the inhibition in mRNA accumulation indicates that the inhibiting activity is mainly post-transcriptional. CMTs were unable to modulate TNF-alpha and IL-10 synthesis and they were not effective in modifying the transcription of relative mRNA in J774 macrophages. On the contrary, IL-12 mRNA expression was significantly increased by CMT-1 and CMT-8 with LPS activation. Since IL-12 protein secretion was inhibited by CMTs, these compounds interfere in the blocking of post-transcriptional events. The studies on cell viability showed that various CMTs induced a dose-dependent decrease in J774 macrophage viability. The cytotoxic activity was present even though NO production was inhibited by CMTs. These compounds appear to be able to activate apoptosis in aNO-independent way. Altogether, these results indicate that CMTs can exert anti-inflammatory effects by inhibiting NO synthesis, and they are able to modify cell viability by exerting a strong apoptotic activity.

Acridine Orange↗