Estimation of impurity profiles of drugs and related materials Part 18. Impurities and degradation products of mazipredone

Reversed-phase HPLC methods using C-18 and C-8 columns as well as various isocratic and gradient systems with aqueous ammonium acetate, methanol and acetonitrile are described for the separation of the impurities of mazipredone (11beta,17-dihydroxy-21-(4-methyl-1-piperazinyl)-pregna-1,4-diene- 3,20-dione hydrochloride). These methods were used also for the estimation of the hydrolytic and oxidative degradation pathways of mazipredone in 0.1 M hydrochloric acid and sodium hydroxide at 80 degrees C. With the aid of HPLC-(APCI)-MS and HPLC-diode-array UV techniques 15 impurities and degradation products have been identified.     

Sensing humor: Latency and amplitude of response related to MMPI profiles.

48 male high school graduates responded to cartoons by (1) sorting 1 set into 4 equal piles ranging from most funny to least funny, and (2) reacting immediately to each cartoon of another set by manipulating a knob. The Ss were divided, according to their MMPI profiles, into PPd (highest score on the Psychopathic Deviate scale), and NPPd (highest score on some other scale). Consistent with expectations, PPd Ss preferred sexual (and hostile) humor more than NPPd Ss, preferred sexual and hostile humor more than nonsense humor, and responded to all cartoons more quickly than NPPd Ss. The immediate reaction measures of latency and amplitude appear to hold promise for future research on humor. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of 19-nor-5,7,9(10)-cholestatrien-3 beta-ol in patients with Smith-Lemli-Opitz syndrome

We have identified the third unknown sterol in the plasma and tissues of Smith-Lemli-Opitz homozygotes as 19-nor-5,7,9(10)-cholestatrien-3 beta-ol. The structure was established from capillary gas-liquid chromatography retention index and characteristic fragmentation pattern by mass spectrometry that were identical to a synthetic reference standard. Evidence is presented that 19-nor-5,7,9(10)-cholestatrien-3 beta-ol is not an artifact formed during the chemical isolation of the relatively unstable 7-dehydrocholesterol. It is possible that 19-nor-5,7,9(10)-cholestatrien-3 beta-ol may contribute to the clinical abnormalities in patients with Smith-Lemli-Opitz syndrome.     

Analysis of the low part of stress-strain curves in rat skin. Influence of age and desmotropic drugs

Stress-strain behaviour of skin strips in rats at different ages or after treatment with prednisolone or D-penicillamine has been analyzed. Special attention has been paid to the lower part of the stress-strain curves. A "hump" at an extension degree of 30% of original length was noted. When rats of different ages were compared this phenomenon was observed predominantly at an age of 2 months. Futhermore, this hump was remarkable in rats treated with prednisolone. When the stress-strain curves of rats at different ages or after treatment were averaged and normalized, the most pronounced deviations were found at an age of 2 months or after prednisolone treatment. The maximum of deviation from Hooke's law occurred at a relative extension degree of 70%. Thus, the maturation process and the influence of corticosteroid affected mostly the second part of the stress-strain curve. In order to evaluate further the stress-strain curves 3 consecutive tangents of the stress-strain curves indicating modules of elasticity were evaluated. The first and second modules of elasticity showed a minimum at an age of 2 months, whereas the ultimate elasticity modules increased with maturation up to a maximum at 12 months followed by a decrease similar to that observed in tensile strength at an age of 24 months.     

Stages of change in psychotherapy: Measurement and sample profiles.

Developed a test designed to measure 4 stages of change hypothesized to account for a temporal dimension in the change process occurring in psychotherapy: (1) precontemplation, (2) contemplation, (3) action, and (4) maintenance. An initial pool of items was reduced to a final test of 32 items on the basis of principal components analysis, Chronbach's coefficient alpha, and item analysis results. 155 Ss commencing psychotherapy were administered the questionnaire; they returned it before their 3rd therapy session. A cluster analysis was performed on the standardized scores for each S on each of the 4 scales. The resulting 18-cluster solution produced 7 major and 2 minor client profiles that were highly distinct and that represented 90% of the Ss. (13 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis. Protein S Study Group

Protein S is a protein C-dependent and independent inhibitor of the coagulation cascade. Deficiency of protein S is an established risk factor for venous thromboembolism. We have used a strategy of specific amplification of the coding regions and intron/exon boundaries of the active protein S gene (PROS1) and direct single-strand solid phase sequencing, to seek mutations in 35 individuals with phenotypic protein S deficiency. Nineteen point mutations (16 novel) in 19 probands (or relatives of probands) with venous thromboembolism are reported here. Fifteen of the 19 mutations were expected to be causal and included 10 missense mutations (Lys9Glu, Glu26Ala, Gly54Glu, Cys145Tyr, Cys200Ser, Ser283Pro, Gly340Asp, Cys408Ser, Ser460Pro, and Cys625Arg). Three of the 15 mutations resulted in premature stop codons (delete T 635 producing a stop codon at position 126, Lys368stop and Tyr595stop) and two were at intron/exon boundaries (+1 G to A in intron d and +3 A to C in intron j). Of the remaining four mutations, three were within intronic sequence and one was a silent mutation within the coding region and did not alter amino acid composition. In two of the 10 missense mutations, reduced plasma protein S activity compared with antigen level suggested the presence of variant (type II) protein S.     

Comparison of the fatty acid compositions in intraepithelial and infiltrating lesions of the cervix: part II, free fatty acid profiles

Clinical studies report a low incidence of intestinal side effects with transdermally administered fentanyl (TTS-fentanyl) in comparison with oral morphine. To support these clinical data, analgesic and intestinal effects of both opioids were compared in rats. After subcutaneous injection, analgesia in the tail withdrawal reaction test was obtained at a peak effect dose of 0.032 mg/kg with fentanyl and 8.0 mg/kg with morphine. This analgesic dose exceeded the ED50 for inhibition of castor oil-induced diarrhea only slightly (1.1 x) in the case of fentanyl (0.028 mg/kg) but markedly (36 x) in the case of morphine (0.22 mg/kg). To reverse completely the antidiarrheal effect of equivalent analgesic doses of the opioids (their ED50S for analgesia lasting 2 hours), much more naloxone was required in the case of morphine (5.4 mg/kg) than in the case of fentanyl (0.19 mg/kg). After oral administration, the difference between both opioids was less pronounced. Analgesia was obtained at 0.85 mg/kg with fentanyl and 32 mg/kg with morphine. This analgesic dose only slightly (1.7 x) exceeded the antidiarrheal dose in the case of fentanyl (0.49 mg/kg) but significantly (6.2 x) in the case of morphine (5.2 mg/ kg). To reverse completely the antidiarrheal effect of equivalent analgesic oral doses of the opioids (their ED50S for analgesia lasting 2 hours), more naloxone was required in the case of morphine (11 mg/kg) than in the case of fentanyl (2.0 mg/kg). Rapid penetration of fentanyl into the brain is thought to be responsible for small dissociation between the analgesic and intestinal effect of this lipophilic opioid. The present data provide preclinical evidence to support the relatively low incidence of intestinal side effects observed clinically with the use of TTS-fentanyl in comparison with orally administered morphine.     

A model of post-combustion in iron-bath reactors,part 3: theoretical basis for post-combustion with pre-heated air

This paper describes the post-combustion of carbon monoxide with pre-heated air, heat transfer from gas to melt via a mixture of metal and slag droplets, the microkinetics of reoxidation of metal droplets in the gas consisting of CO₂, CO and N₂, and the total heat and mass balance in the gas space and in the iron-bath. The computer program presented here Is flexible and can simulate various process modes of iron-bath reactors. The production rate of the reactor and the carbon consumption can be calculated herewith.     

Perception of speed in an automobile: Estimation and production.

In 2 experiments, the authors studied the perception of speed in an automobile as a function of speed, previous acceleration, trajectory, driving experience, and sex of the participants. Three levels of driving experience were observed: nondrivers, new drivers, and experienced drivers. In Experiment 1, 60 participants verbally estimated the speed at which they traveled by car. In Experiment 2, 30 participants performed an active estimation task with an accelerator to produce a target speed, in addition to the same passive verbal estimation. The results showed a tendency to underestimate speed, and this effect was more pronounced at lower speeds. The predicted overcompensation in the active production task confirmed the general equivalence of both passive and active estimation despite certain differences. Results are discussed from a psychophysical viewpoint, and implications for driving behavior are also considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

WISC-IV profiles in children with traumatic brain injury: Similarities to and differences from the WISC-III.

The Wechsler Intelligence Scale for Children—Fourth Edition (WISC–IV; D. Wechsler, 2003a) is often utilized to assess children with traumatic brain injury (TBI), although little information is available regarding its psychometric properties in these children. The current study examined WISC–IV performance in a sample of 61 children with TBI. As compared to the standardization sample, results indicated that the TBI group exhibited relative deficits on all subtest and index scores, with the greatest deficits on the Processing Speed Index (PSI) and Coding subtest scores. However, the Perceptual Reasoning Index score was not uniquely sensitive to brain injury, and the Cognitive Processing Index score was less sensitive to TBI than the PSI score. Also, the PSI did not uniquely predict learning and memory abilities, as had been reported in previous studies of the Wechsler Intelligence Scale for Children—Third Edition (WISC–III; D. Wechsler, 1991). The present findings indicate substantive differences between the WISC–III and WISC–IV profiles of children with TBI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multidimensional Personality Questionnaire profiles of veterans with traumatic combat exposure: Externalizing and internalizing subtypes.

This study used the Multidimensional Personality Questionnaire (MPQ; A. Tellegen, in press) to identify personality-based subtypes of posttraumatic response. Cluster analyses of MPQs completed by combat veterans revealed subgroups that differed on measures relating to the externalization versus internalization of distress. The MPQ profile of the externalizing cluster was defined by low Constraint and Harmavoidance coupled with high Alienation and Aggression. Individuals in this cluster also had histories of delinquency and high rates of substance-related disorder. In comparison, the MPQ profile of the internalizing cluster was characterized by lower Positive Emotionality, Alienation, and Aggression and higher Constraint, and individuals in this cluster showed high rates of depressive disorder. These findings suggest that dispositions toward externalizing versus internalizing psychopathology may account for heterogeneity in the expression of posttraumatic responses, including patterns of comorbidity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)