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In a cross-sectional study of injection site leakage of fluphenazine decanoate in 40 psychiatric outpatients, significantly more leakage occurred after intramuscular than after subcutaneous injection. Results of the study suggest that age, sex, body mass, and injection volume may also affect leakage.
A novel, rapid, and continuous online concentration approach based on field-amplified sample injection for the analysis of fangchinoline and tetrandrine was developed in this paper by combination of flow injection-MEKC. The BGE used was a solution composed of 75 mM H3PO4-triethylamine-2.5% v/v polyoxyethylene sorbitan monolaurate-20% v/v methanol buffer (pH* 5.0). The analytes prepared in 50% v/v aqueous ethanol were used as the test analytes. Sample was injected electrokinetically between plugs of water. When the cations reached the boundary between the water plug and BGE, they slowed down and became concentrated. Thereafter, MEKC was initiated for the separation. This results in 6.8-8.9-fold improvement in concentration sensitivity relative to conventional CE methods. The separation could be achieved within 10 min and sample throughput rate can reach up to 50/h. The repeatability (defined as RSD) was 4.8, 4.4% with peak height evaluation and 3.6, 0.94% with peak area evaluation for TET and FAN, respectively.
2,4-Dithiobiuret (DTB) is a sulfonated derivative of urea that is used as a reducing agent in chemical manufacture. Its low acute toxicity to rodents belies a peripherally mediated, delayed-onset muscle weakness which develops during repeated daily exposure. In experiment 1, a standard dose regimen of DTB (0.5 mg/kg per day IP for 5 days) was used to induce motor dysfunction as a way to dissociate peripheral and central influences on a test of cognitive and motor function in rats. Sixteen male rats were trained to perform a Delayed Matching-to-Position/Visual Discrimination (DMTP/VD) task which permits quantification of working memory (matching accuracy), reference memory (discrimination accuracy), and motor function (choice response latency and nosepoke inter-response time, IRT). The first dose of DTB significantly increased matching accuracy; during the following week, DTB reduced matching accuracy, increased choice response latency and nosepoke IRT, and reduced trial completion. Discrimination accuracy remained unaffected. Experiment 2 explored the effects of single administrations of DTB on DMTP/VD. Sixteen other trained rats were divided into two groups with equal matching accuracy. One group received DTB (0.5,1.0, and 2.0 mg/kg, IP) in separate injections at least 1 week apart; the other group received vehicle at the same times. Matching accuracy increased significantly in the treated rats and not in the controls following each dose of DTB. The magnitude of this increase was dose dependent, and lasted from 1 to 8 weeks after each injection. Discrimination accuracy, response latency, nosepoke IRT and trial completion remained unaffected throughout the study. After DTB, matching accuracy was less easily disrupted by scopolamine (0.1-0.3 mg/kg, IP). However, DTB did not alter the rats' response to reducing the distance between the response levers, to reversal of the matching rule to a nonmatching rule, or to challenge with MK-801 (0.05-0.10 mg/kg, IP). These data indicate that acute DTB causes a long-lasting facilitation of working memory in rats in the absence of any of the indications of motor impairment which follow repeated, daily injections of the chemical.
Addition of the non-ionic detergent Nonidet P-40 (NP-40) to horseradish peroxidase (HRP) injected in small quantities into barrelfields of mouse somatosensory cortex results in a significant increase of labeled neurons in the contralateral barrelfield cortex as compared to normal HRP. Comparisons with lysolethicin as an additive to HRP show that with NP-40 neurons are labeled more reliably and spread of label is less extensive at the injection site. Using NP-40, the region of dense label spread at the injection site as revealed by the diaminobenzidine/cobalt procedure coincides rather precisely with the contralateral cortical region containing labeled neurons as visualized by tetramethylbenzidine.
Jet injectors employ high-velocity liquid jets that penetrate into human skin and deposit drugs in the dermal or subdermal region. Although jet injectors have been marketed for a number of years, relatively little is known about the interactions of high-speed jets with soft materials such as skin. Using polyacrylamide gels as a model system, the mechanics of jet penetration, including the dependence of jet penetration on mechanical properties, was studied. Jets employed in a typical commercial injector, (orifice diameter: 152 microm, velocity: 170-180 m/s) were used to inject fluid into polyacrylamide gels possessing Young's moduli in the range of 0.06-0.77 MPa and hardness values in the range of 4-70 H(OO). Motion analysis of jet entry into polyacrylamide gels revealed that jet penetration can be divided into three distinct events: erosion, stagnation, and dispersion. During the erosion phase, the jet removed the gel at the impact site and led to the formation of a distinct cylindrical hole. Cessation of erosion induced a period of jet stagnation ( approximately 600 micros) characterized by constant penetration depth. This stage was followed by dispersion of the liquid into the gel. The dispersion took place by crack propagation and was nearly symmetrical with the exception of injections into 10% acrylamide (Young's modulus of 0.06 MPa). The penetration depth of the jets as well as the rate of erosion decreased with increasing Young's modulus. The mechanics of jet penetration into polyacrylamide gels provides an important tool for understanding jet injection into skin.
Using mice as a model, we recently reported that the long-circulating properties of polyethylene glycol (PEG) (M.W. 2000)-modified liposomes (mPEG(2000)-liposomes) disappeared when they were intravenously injected at certain intervals [referred to as the "accelerated blood clearance (ABC) phenomenon"]. Herein, we report on a study of issue of whether physicochemical properties of a prior dose of liposomes such as degree of PEGylation, PEG chain length, lipid dose, surface charge, size, play a role in inducing this phenomenon. The injection of conventional liposomes (without a PEG-coating) significantly induced the phenomenon. The PEGylation of conventional liposomes attenuated the induction of the phenomenon somewhat with increasing molar content of PEG derivative and PEG chain length. These findings clearly suggest that the PEGylation of liposomes are not the major cause of the ABC phenomenon but, rather, played a role in preventing it. In addition, increasing the lipid dose in a prior dose of mPEG(2000)-liposomes (0-25 micromol/kg) increased the induction of the phenomenon in a sigmoid manner. The surface charge and size of the liposomes were not critical for the induction of the phenomenon, although generally these serve as determinants in the biodistribution of liposomes. The results reported here clearly indicate that the physicochemical properties of a prior dose of liposomes strongly affect the pharmacokinetic behavior of a subsequent injection of mPEG(2000)-liposomes: The extent of PEGylation and the lipid dose had an effect, but the surface charge and size did not. The results reported herein have a considerable impact on the design and engineering of liposomal formulations for use in multiple drug therapy as well as in therapy that involves the use of liposomal drugs.
A bead injection spectroscopy-flow injection analysis (BIS-FIA) system for the spectrophotometric detection of promethazine and trifluoperazine is developed. The sensor is based in the oxidation of the phenothiazines by Fe(III) which is later determined by formation of the complex between Fe(II) and Ferrozine, [FeFz(3)](4-). Immediately, this complex is retained on a homogeneous bead suspension of Sephadex QAE A-25 resin (500 microl) which has been injected previously in the system to fill a commercial flow-cell (Hellma 138-OS). The use of BI with respect to the use of a reusable flow-through sensor is justified because the complex is so strongly retained on the beads that the regeneration of the solid support becomes extraordinarily difficult in the proposed method. At the end of the analysis, beads are automatically discarded from the flow-cell, by reversing the flow, and transported out of the system. The analytical signals are measured at a wavelength of 567 nm, corresponding to the absorbance of the complex. Using a sample volume of 600 microl, the analytical signal showed a very good linearity in the range 0.5-8.0 microgml(-1) and 0.5-10.0 microgml(-1), with detection limits of 0.09 and 0.14 microgml(-1) for promethazine and trifluoperazine, respectively. R.S.D.s (%) lower than 2% were obtained for both analytes. The proposed method is highly selective in the presence of other species that are normally encountered with these analytes. The sensor was satisfactorily applied to pharmaceutical preparations.
An adequate understanding of the inflammatory mechanisms following intraperitoneally-injected oil-adjuvanted vaccines in fish is required for the improvement of the quality of vaccines. We report the findings of a study in which the importance of neutrophils, macrophages, lymphocytes and mast cells (MCs) in early inflammatory reactions of Atlantic salmon were examined in comparison with those of rainbow trout and grayling. The inflamed areas in the pylorus/pancreas area (injection site) were sequentially measured using computer-assisted microscopy, parallel with the quantification of leucocytes from 2 to 16 weeks post-vaccination. Antigen retention was also evaluated. Results show that inflammation in Atlantic salmon was slow to develop and was associated with a prolonged initial dominance of neutrophils. In contrast, the onset in rainbow trout was rapid and strong with early macrophage domination. The inflammatory and cellular response in grayling was initially in-between but progressed to be the strongest at 16 weeks. The results suggest that slow development of inflammation in Atlantic salmon and grayling leads to delayed sequestration of antigens resulting in chronically active inflammation that attempts to remove the antigens from the injection site. The strong onset in rainbow trout leads to rapid breakdown and removal of antigens resulting in early resolution.
Effects of intra-medial septum injections of L-arginine, a precursor of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, and sulpiride, a selective antagonist of dopamine D2 receptor on morphine-induced conditioned place preference (CPP) in male Wistar rats were examined. Using a 3-day schedule of conditioning, morphine (0.5-7.5 mg/kg, s.c.) produced a significant place preference in a dose-dependent manner. The maximum response was observed with 5.0 mg/kg of opioid. Sulpiride (0.3, 1.0 and 3.0 microg/rat), but not L-arginine (0.3, 1.0 and 3.0 microg/rat) or L-NAME (0.3, 1.0 and 3.0 microg/rat), in combination with morphine (5.0 mg/kg), during conditioning, significantly altered morphine-induced CPP. Single doses (0.3, 1.0 and 3.0 microg/rat) of either L-arginine or L-NAME, during conditioning, did not induce CPP. Sulpiride at 0.3-3.0 microg/rat, intra-medial septum, during conditioning, produced a significant conditioned place aversion. Intra-medial septum injections of L-arginine but not L-NAME or sulpiride, 1-2 min before testing, increased the expression of morphine-induced CPP. The administration of sulpiride (0.3, 1.0 and 3.0 microg/rat), but not L-NAME (0.3, 1.0 and 3.0 microg/rat), 1-2 min before the injection of L-arginine (0.3 microg/rat) on day of test, significantly attenuated the response to L-arginine. L-Arginine (0.3-3.0 microg/rat), during conditioning, showed a statistically significant increase in locomotor activity compared with that to control group. Moreover, sulpiride decreased locomotion by itself or in combination with morphine during conditioning and on the test day of morphine CPP. It can be concluded that L-arginine, a precursor of nitric oxide, in the rat median septum may play a role in expression of morphine conditioning due to dopamine release in this area.
The results from a User Satisfaction Questionnaire, Treatment Assessment Questionnaire, and Global Well-Being Schedule questionnaire administered to women participating in an open-labeled, nonrandomized, parallel, controlled study comparing a new monthly injectable contraceptive containing 25 mg of medroxyprogesterone acetate (MPA) and 5 mg of estradiol cypionate (E2C) (MPA/E2C) (Lunelle Monthly Contraceptive Injection) and a triphasic norethindrone (0.5, 0.75, 1.0 mg)/0.035 mg ethinyl estradiol (NET/EE) oral contraceptive (Ortho-Novum 7/7/7) are reviewed. Approximately 85% of all 1103 women enrolled in the comparative trial completed their initial and final questionnaires. To better assess the comparison of a new and extant method of contraception, outcome data were divided among MPA/E2C users and new and previous oral contraceptive (OC) users. Despite the inherent inequalities in comparing an injectable to an oral method of contraception, few treatment assessment and satisfaction outcomes were significantly different when comparing MPA/E2C users to new OC (NET/EE) users. More women in the MPA/E2C study group reported discomfort with their method than women in either NET/EE study group; however, only 19.4% of MPA/E2C users rated the administration of their contraceptive to be moderately uncomfortable or worse, compared to 11.7% of new NET/EE users and 13.4% of previous OC users. Among MPA/E2C users, 86.3% reported no interference with social activities compared with 90.4% of new NET/EE users. MPA/E2C and new NET/EE users were also similar in their responses recommending their respective contraceptive method to friends, with > 90% of both groups stating that they had a very favorable experience and would definitely recommend their method to a friend. In general, MPA/E2C was well accepted by women in the study group. Their attitudes and perceptions are similar to those of women who were starting OCs for the first time. These data support the premise that MPA/E2C may become a well accepted, first-line contraceptive option for women in the US.
Twenty-five patients with a tubal pregnancy were treated by an injection of methotrexate (MTX) into the tubal swelling after vasoconstriction of the mesosalpinx with adrenaline. Twenty-four of the 25 patients had an uneventful clinical course. In one case, the tube ruptured despite falling serum human chorionic gonadotropin (hCG) concentrations. In 17 of 24 patients, the dose of 100 mg that was locally injected was sufficient. Seven patients were given additional systemic injections. In 3 of the 4 patients with high initial serum hCG levels (greater than 10.000 mIU/mL), the clinical course was uneventful. The side effects of MTX and adrenaline were minimal. Whether this way of treatment guarantees better chances of fertility in the future is unknown. Therefore a prospective, case-controlled study comparing the fertility rates in different ways of treatment is needed.
Injectable polytetrafluoroethylene (Teflon) and collagen have inherent problems that may prevent their long-term success. In search of a different injectable biomaterial we confirmed in rabbits the safety of injected Bioglass particles suspended in sodium hyaluronate. A second study was performed testing the ability of the Bioglass suspension to increase urethral resistance in pigs. Bioglass particles in suspension have the potential to substitute for polytetrafluoroethylene or collagen in the treatment of urinary incontinence or vesicoureteral reflux.
A simple coaxial jet mixer for rapid and efficient confluent mixing under laminar flow conditions (Re < 5) is described. This device demonstrates exceptional control of mixing between two laminar streams by creating shear forces due to variable flow velocities at the point of confluence. It is suitable for flow injection and cytometric analyses of rapid kinetic events which require contact mixing of two solutions and subsecond measurements of the evolving reaction. This apparatus was devised for flow injection cytometry as performed on a Becton Dickinson FACS Analyzer. Under normal cytometric conditions and at a sample introduction rate of 60 microL/min, the laminar jet mixer is capable of complete mixing of two solutions within 55 ms. Kinetic measurements can be performed on the FACS Analyzer in a variable time range of 100 ms to 3 min with 14-30 ms temporal resolution of the studied event. Since no boost in core flow is required, potential spectral distortions due to core flow variations are eliminated. This coaxial jet mixer can be easily constructed and employed on a variety of cytometers as well as conventional flow injection analysis systems, since it is an effective mixer under most flow conditions.
In this paper, the third generation of flow injection analysis, also named the lab-on-valve (LOV) approach, is proposed for the first time as a front end to high-performance liquid chromatography (HPLC) for on-line solid-phase extraction (SPE) sample processing by exploiting the bead injection (BI) concept. The proposed microanalytical system based on discontinuous programmable flow features automated packing (and withdrawal after single use) of a small amount of sorbent (<5 mg) into the microconduits of the flow network and quantitative elution of sorbed species into a narrow band (150 microL of 95% MeOH). The hyphenation of multisyringe flow injection analysis (MSFIA) with BI-LOV prior to HPLC analysis is utilized for on-line postextraction treatment to ensure chemical compatibility between the eluate medium and the initial HPLC gradient conditions. This circumvents the band-broadening effect commonly observed in conventional on-line SPE-based sample processors due to the low eluting strength of the mobile phase. The potential of the novel MSFI-BI-LOV hyphenation for on-line handling of complex environmental and biological samples prior to reversed-phase chromatographic separations was assessed for the expeditious determination of five acidic pharmaceutical residues (viz., ketoprofen, naproxen, bezafibrate, diclofenac, and ibuprofen) and one metabolite (viz., salicylic acid) in surface water, urban wastewater, and urine. To this end, the copolymeric divinylbenzene-co-n-vinylpyrrolidone beads (Oasis HLB) were utilized as renewable sorptive entities in the micromachined unit. The automated analytical method features relative recovery percentages of >88%, limits of detection within the range 0.02-0.67 ng mL(-1), and coefficients of variation <11% for the column renewable mode and gives rise to a drastic reduction in operation costs ( approximately 25-fold) as compared to on-line column switching systems.
UNLABELLED: Authors from Seoul describe their experience with patients already on triple therapy by intracavernosal injection who changed to oral sildenafil. Rather surprisingly, they found that patients had had a greater preference than expected for triple therapy, feeling that they had a better quality of erection on intracavernosal injection. The subject of the effect of renal transplantation on sperm quality and sex hormone levels is discussed by authors from Teheran. They found that sperm morphology and density remained unchanged, but there were significant improvements in sperm mobility. There was also an improvement in hormone levels and sexual function. OBJECTIVE: To investigate the efficacy and preference for oral sildenafil or intracavernosal injection (ICI) therapy in patients with erectile dysfunction (ED) already using ICI. PATIENTS AND METHODS: In all, 69 patients with ED (mean age 55.1 years, sd 12.3) on ICI therapy with triple solution (papaverine/phentolamine/prostaglandin-E1) for > 1 year were recruited for the study. Their erection quality, adverse reactions and selection rate of oral sildenafil or ICI as treatment, after using sildenafil for 3 months, and the reasons for their preferences, were compared between the regimens, RESULTS: Overall, 52 men (75%) responded to sildenafil; of these men, the erection quality with ICI was better than that with sildenafil in 46 (89%) and 16 (31%) preferred ICI as their treatment. Eighteen patients (35%) used each treatment alternately and 18 (35%) used sildenafil exclusively. The main reason given by patients for choosing ICI was a better quality of erection (74%). CONCLUSION: More patients with ED and using ICI preferred it as their main treatment than was expected, even though they had a good response to oral sildenafil. A better quality of erection with ICI was the reason why experienced patients chose this method, differing from the choice of patients starting treatment for ED.
BACKGROUND: Conventional ICSI to date was focused only on tail membrane damage to achieve sperm immobilization and disruption of the plasma membrane, even though liberation of soluble sperm factors is achieved by disruption of the sperm head membrane. METHODS: A modified method for ICSI was developed: head membrane-damaged spermatozoa aspirated tail or head first were injected into the ooplasm using a 3-4 micro m diameter injection pipette connected to an open-ended aspiration tube regulated by mouth. The efficiency of this modified ICSI was compared with that of conventional ICSI and IVF. RESULTS: When spermatozoa aspirated tail first were injected, a decondensed sperm head was more frequently observed in the oocyte cytoplasm with the modified ICSI (80.0%) than with conventional ICSI (55.7%) or IVF (63.5%) (P < 0.001). The rates of male pronucleus (MPN) formation in the modified ICSI or IVF were significantly higher (50.7 and 39.7%, respectively) than in conventional ICSI (27.9%) (P < 0.001). The rates of survival, cleavage and embryo development to blastocyst were significantly higher in the modified ICSI (71.7, 60.6 and 17.5%) than in conventional ICSI (48.1, 48.7 and 10.5%) (P < 0.001). No significant differences in MPN formation and embryo development to blastocyst were observed between the tail- and head-first sperm aspiration. CONCLUSION: Our results demonstrated that, in the pig, the procedures of pursuing, capturing and immobilizing a spermatozoon and producing deliberate damage to the tail membrane in conventional ICSI were not required in the modified ICSI. We believe that the present study provides sufficient technical advancement to replace conventional ICSI with the modified ICSI, which is more effective and also avoids unnecessary procedures involved in conventional ICSI.
PURPOSE: Our goal was to evaluate several fast MR strategies for monitoring ethanol distributions so that percutaneous ethanol injection might be guided with MRI. METHOD: Fast RF spoiled GRE sequences (SPGR) and T2-weighted rapid acquisition with relaxation enhancement (RARE) sequences with and without spectroscopic-quality water suppression techniques were assessed for their ability to depict the distribution of injected ethanol in ex vivo pig liver. A line scan Carr-Purcell-Meiboom-Gill spectroscopic imaging sequence was used to validate observations and measure spectral relaxation characteristics of the ethanol signal in liver. Injected deuterated ethanol was also tested as an alternative possibility to depict the distribution of ethanol. RESULTS: The water-suppressed T2-weighted RARE sequence depicted the distribution of ethanol better than other sequences. Deuterated ethanol appeared as a signal void on all sequences. CONCLUSION: Water-suppressed T2-weighted RARE sequences could be useful to rapidly monitor MR-guided PEI.
In Minnesota, state legislation, enacted July 1998, provided for voluntary pharmacy sales of syringes/needles without a prescription for an accompanying drug. The goal was to stem HIV transmission among injecting drug users (IDUs) by providing greater access to sterile syringes. We used a pre/post evaluation design to investigate the impact of less restrictive syringe/possession laws on IDUs' HIV-related syringe practices. Independent cross-sectional samples of IDUs were recruited from street sites and a correctional facility immediately before and 1 year after enactment of the laws. Of the 671 IDUs interviewed, 570 (270 prelegislation and 300 postlegislation) had injected at least once in the 30 days before the interview. IDUs were more likely to purchase syringes at pharmacies after enactment of the laws (odds ratio [OR], 2.66; 95% confidence interval [CI], 1.83-3.85), yet did not change their behaviors regarding carrying unused syringes (OR, 0.90; 95% CI, 0.63-1.28). After adjusting for speedball injection and criminal history, syringe sharing decreased among IDUs (adjusted OR, 0.67; 95% CI, 0.45-1.00) yet syringe reuse remained the same (adjusted OR, 0.67; 95% CI, 0.40-1.11). Safe disposal of syringes did not differ significantly across the sampling periods (adjusted OR, 1.32; 95% CI, 0.84-2.06). Increased access to pharmacy syringes offers a first step at reducing HIV-related syringe practices but must be coupled with strong HIV prevention messages, drug treatment referrals, and safe syringe disposal options.