Methcathione ("cat"): an enantiomeric potency comparison

With regard to its chemical structure, methcathinone is to cathinone what methamphetamine is to amphetamine. Although it is a drug of abuse outside the United States, methcathione is only recently making an appearance on the clandestine market in this country and has just been classified a Schedule I substance under the Emergency Scheduling Act. We have previously demonstrated that racemic methcathinone produces locomotor stimulation in mice, and substitutes for cocaine and (+)amphetamine in rats trained to discriminate either cocaine or (+)amphetamine, respectively, from saline in tests of stimulus generalization. Because an enantiomeric potency comparison has never been reported for the optical isomers of methcathinone, in the present investigation we synthesized samples of S(-)- and R(+)methcathinone and compared them for their ability: a) to produce locomotor stimulation in mice, b) to elicit cocaine-like responding in rats trained to discriminate 8.0 mg/kg of cocaine from saline vehicle, and c) to elicit (+)-amphetamine-appropriate responding in rats trained to discriminate 1.0 mg/kg of (+)amphetamine from saline vehicle. S(-)Methcathinone was about twice as potent as S(+)amphetamine and three to five times more potent than R(+)methcathinone in the three pharmacologic assays. We conclude that both optical isomers possess central stimulant character, but that S(-)methcathinone is somewhat more potent than R(+)methcathinone.     

Live attenuated SIV vaccines are not effective in a postexposure vaccination model

We examined the immunohistochemical expression of proliferating-cell nuclear antigen (PCNA) and p53 proteins in dysplasia and intramucosal carcinoma of the esophagus. Immunohistochemistry was performed with monoclonal antibodies directed against PCNA and p53. We used surgically resected specimens from 29 patients who had a total of 55 lesions of severe dysplasia (n = 16), intraepithelial carcinoma (n = 21), and mucosal carcinoma (n = 18). The mean PCNA index with immunoreactivity for p53 was 48.9 +/- 6.5 in areas of severe dysplasia (n = 7), 58.2 +/- 7.3 in areas of intraepithelial carcinoma (n = 10), and 71.4 +/- 9.3 in the invasive areas of mucosal carcinoma (n = 10). The mean PCNA index without immunoreactivity for p53 was 41.2 +/- 5.5 in areas of severe dysplasia (n = 9), 48.0 +/- 7.4 in areas of intraepithelial carcinoma (n = 11), and 63.7 +/- 9.1 in invasive areas of mucosal carcinoma (n = 8). The PCNA indices of the areas of severe dysplasia with immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma with immunoreactivity for p53. Similarly, the PCNA indices of severe dysplasia without immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma without immunoreactivity for p53. These results thus suggest that severe dysplasia has a lower proliferative potential than carcinoma and may therefore represent a precancerous lesion.     

Positron-annihilation study of oxygen-deficient YBa2Cu3Ox (6.3

CQ Tang  BR Li  A Chen 《Canadian Metallurgical Quarterly》1990,42(13):8078-8080

Vitrectomy for retained lens fragments after phacoemulsification

PURPOSE: Posterior lens fragments after phacoemulsification can be a serious complication of cataract surgery. This study is designed to evaluate the clinical features of eyes after pars plana vitrectomy has been performed to remove posteriorly dislocated lens fragments after phacoemulsification. METHODS: The authors performed a retrospective chart review of 126 consecutive eyes of 126 patients with dislocated lens fragments after phacoemulsification, managed with pars plana vitrectomy at Associated Retinal Consultants of Michigan. These eyes were operated on from January 1986 through January 1996. RESULTS: The relation of the intervals between cataract surgery and vitrectomy to various postoperative clinical parameters was studied. Clinical features at presentation included elevated intraocular pressure (IOP over 25 mmHg) in 52.4% of the eyes, uveitis in 69.6%, and corneal edema in 50.8%. Initial visual acuity was 20/400 or worse in 73.8% of the eyes. The mean preoperative visual acuity was 20/278 (median, 20/400), whereas the mean final visual acuity was 20/40 (median, 20/50) after a mean follow-up of 18.9 months. Retinal detachments were found in 20 eyes: 7 before vitrectomy and 13 during or after it. After surgery, 44% of eyes achieved a final visual acuity of 20/40 or better and 90% were 20/400 or better. The distribution of best-corrected final visual acuities among the eyes showed statistically significant differences based on the type of intraocular lens (IOL) used, with posterior chamber IOL greater than anterior chamber IOL, and anterior chamber IOL greater than aphakia. Reasons for a poor visual outcome included persistent corneal edema (four eyes), retinal detachment (two eyes), central retinal vein occlusion (two eyes), age-related macular degeneration (two eyes) glaucoma (one year), and endophthalmitis (one eye). CONCLUSIONS: There were no statistically significant differences between early (< 7 days) and delayed (8 days or more) vitrectomy when increased IOP, corneal edema, choroidal effusions, cystoid macular edema, and visual acuity were analyzed. The use of vitrectomy to remove posteriorly dislocated lens fragments has been shown to be an effective treatment method that significantly reduces the inflammatory response and hastens visual recovery.     

Multifunction MMIC history from a process technology perspective

The different types of multifunction microwave monolithic integrated circuits (MMICs) that have been developed to date are reviewed, and projections for the future direction of the technology are made. Various innovative circuit design techniques have allowed a wide range of functions to be performed using the same processes as single-function MMICs. These circuits are almost exclusively based on GaAs Schottky-barrier-gate ion-implanted MESFETs, MIM capacitors, inductors, and (sometimes) through-substrate vias on GaAs substrates. Chips performing all the microwave functions of radar transmit/receive modules, receivers, and frequency synthesizers have been developed. Process complexity is a dominant factor determining their practicality and cost, and the most successful circuits have been designed with process limitations in mind. In the future, proliferation of multifunction MMICs with even greater functional complexity is expected, but additional process complexities will be added sparingly     

Sequential addition of temperature-sensitive missense mutations into the PB2 gene of influenza A transfectant viruses can effect an increase in temperature sensitivity and attenuation and permits the rational design of a genetically engineered live influenza A virus vaccine

We have previously described a strategy for the recovery of a synthetic influenza A virus wild-type (wt) PB2 gene (derived from influenza A/Ann Arbor/6/60 [AA] virus) into an infectious virus. It was possible to introduce an attenuating temperature-sensitive (ts) mutation at amino acid residue 265 of the AA wt PB2 gene and to rescue this mutant gene into infectious virus. Application of this new technology to influenza A virus vaccine development requires that multiple attenuating mutations be introduced to achieve a satisfactorily attenuated virus that retains the attenuation (att) phenotype following replication in vivo. In this report, we demonstrate that putative ts mutations at amino acids 112, 556, and 658 each indeed specify the ts and att phenotypes. Each of these mutations was introduced into a cDNA copy of the AA mutant mt265 PB2 gene to produce three double-mutant PB2 genes, each of which was rescued into an infectious virus. In general, the double-mutant PB2 transfectant viruses were more ts and attenuated in the lower respiratory tracts of hamsters than the single-mutant transfectant viruses, and the ts phenotype of two of three double-mutant PB2 transfectant viruses was stable even after prolonged replication in the upper respiratory tracts of immunocompromised mice. Two triple-mutant PB2 transfectant viruses with three predicted amino acid substitutions resulting from five nucleotide substitutions in the cDNA were then generated. The triple-mutant PB2 transfectant viruses were more ts and more attenuated than the double-mutant PB2 transfectant viruses. These results indicate that sequential introduction of additional ts mutations into the PB2 gene can yield mutants that exhibit a stepwise increase in temperature sensitivity and attenuation compared with the preceding mutant(s) in the series. Furthermore, the level of temperature sensitivity of the transfectant viruses correlated significantly with the level of attenuation of these viruses in hamsters. Although the triple-mutant PB2 transfectant viruses were attenuated in hamsters, intranasal administration of these viruses elicited a vigorous serum hemagglutination-inhibiting antibody response, and this was associated with resistance of the lower respiratory tract to subsequent wt virus challenge. These observations suggest the feasibility of using PB2 reverse genetics to generate a live influenza A virus vaccine donor strain that contains three attenuating mutations in one gene. It is predicted that reassortant viruses derived from such a donor virus would have the properties of attenuation, genetic stability, immunogenicity, and protective efficacy against challenge with wt virus.     

Humeral epicondylitis among gas- and waterworks employees

OBJECTIVES: In this cross-sectional study 290 male employees of the public gas- and waterworks of Hamburg, Germany, were examined for symptoms of epicondylitis. Forty-one workers were diagnosed with symptoms of lateral or medial epicondylitis. The effect of employment in different job categories on the prevalence of epicondylitis was explored. METHODS: The diagnosis of epicondylitis was based on the study's own criteria and compared with criteria used in former studies. Jobs were categorized into high, moderate, and no exposure groups according to tasks regarded as strenuous for the elbow. The data were analyzed with the help of multivariate logistic regression. RESULTS: With the study's diagnostic criteria, the prevalence odds ratio (OR) for 10 years of high exposure to elbow straining work was 1.7 [95% confidence interval (95% CI) 1.04-2.68] for currently held jobs and 2.16 (95% CI 1.08-4.32) for formerly held jobs. For workers regarded as moderately exposed in current jobs the odds ratio for 10 years was 1.4 (95% CI 1.00-1.93). Very similar results were obtained for current exposure when stricter diagnostic criteria were employed. CONCLUSIONS: The results suggest a cumulative exposure effect with length of employment. Workers with high exposure in former jobs compared with employees with high exposure in their current job exhibited more residual or slight epicondylitis symptoms upon examination.     

Risk characterization of methyl tertiary butyl ether (MTBE) in tap water

Methyl tertiary butyl ether (MTBE) can enter surface water and groundwater through wet atmospheric deposition or as a result of fuel leaks and spills. About 30% of the U.S. population lives in areas where MTBE is in regular use. Ninety-five percent of this population is unlikely to be exposed to MTBE in tap water at concentrations exceeding 2 ppb, and most will be exposed to concentrations that are much lower and may be zero. About 5% of this population may be exposed to higher levels of MTBE in tap water, resulting from fuel tank leaks and spills into surface or groundwater used for potable water supplies. This paper describes the concentration ranges found and anticipated in surface and groundwater, and estimates the distribution of doses experienced by humans using water containing MTBE to drink, prepare food, and shower/bathe. The toxic properties (including potency) of MTBE when ingested, inhaled, and in contact with the skin are summarized. Using a range of human toxic potency values derived from animal studies, margins of exposure (MOE) associated with alternative chronic exposure scenarios are estimated to range from 1700 to 140,000. Maximum concentrations of MTBE in tap water anticipated not to cause adverse health effects are determined to range from 700 to 14,000 ppb. The results of this analysis demonstrate that no health risks are likely to be associated with chronic and subchronic human exposures to MTBE in tap water. Although some individuals may be exposed to very high concentrations of MTBE in tap water immediately following a localized spill, these exposures are likely to be brief in duration due to large-scale dilution and rapid volatilization of MTBE, the institution of emergency response and remediation measures to minimize human exposures, and the low taste and odor thresholds of MTBE which ensure that its presence in tap water is readily detected at concentrations well below the threshold for human injury.