Effective use of ribonucleotide reductase inhibitors (Didox and Trimidox) alone or in combination with didanosine (ddI) to suppress disease progression and increase survival in murine acquired immunodeficiency syndrome (MAIDS)

Ribonucleotide reductase inhibitors (RRIs) have been recently shown to inhibit retroviral replication. We examined a new series of RRIs, 3,4-dihydroxybenzohydroxamic acid (Didox) and 3,4,5-trihydroxybenzohydroxamidoxime (Trimidox) for their ability to alter disease progression in murine acquired immunodeficiency syndrome (MAIDS), both alone and in combination with 2',3'-dideoxyinosine (ddI). MAIDS disease was induced by inoculation of female C57BL/6 mice with the LP-BM5 murine leukemia virus (MuLV) and disease progression characterized by extensive peripheral lymphadenopathy and splenomegaly. Efficacy of treatment with these drugs was based upon their ability to influence survival and disease pathophysiology by monitoring the development of splenomegaly. Toxicity was determined by changes in body weight, total peripheral white blood cell count and hematocrit. Didox or trimidox monotherapy was associated with increased survival and decreased disease pathophysiology, with no apparent toxicity. Combined with ddI, their ability to reduce development of viral induced splenomegaly was enhanced compared to trimidox, didox or ddI alone. These results demonstrate RRIs have potent activity in reversing the disease manifestations characteristic of MAIDS. Further studies are warranted to determine human clinical efficacy.     

Orthopaedic surgery in hemophilic patients with human immunodeficiency virus

Patients registered at the author's hemophilia center between 1982 and 1994 were studied to establish whether major orthopaedic surgical procedures accelerate the fall of CD4 lymphocyte counts of patients with hemophilia who are infected with the human immunodeficiency virus, and whether patients who had surgery had different rates of development of acquired immune deficiency syndrome or death when compared with patients who did not have surgery. The patients were divided into four groups: Group 1, 22 patients who were human immunodeficiency virus positive undergoing orthopaedic surgery; Group 2, 89 patients who were human immunodeficiency virus positive not undergoing orthopaedic surgery; Group 3, 18 patients who were human immunodeficiency virus negative undergoing orthopaedic surgery; and Group 4, 135 patients who were human immunodeficiency virus negative not undergoing orthopaedic surgery. There was no significant difference between the rates of decline of CD4 lymphocyte counts for patients who were human immunodeficiency virus positive who underwent surgery when compared with human immunodeficiency virus positive patients who did not undergo surgery, nor was there any significant difference between the two human immunodeficiency virus negative groups. There were no significant differences in the rate of development of acquired immune deficiency syndrome or mortality rates between patients who had surgery and those who did not.     

Assessment of childhood phobias

Childhood phobias can be successfully treated using a variety of behavioral strategies, provided there has been a psychometrically sound assessment. Measures are also important for the evaluation of treatment efficacy and the testing of hypotheses generated by new ideas and theories of children's phobias. This paper outlines broad-based assessment procedures used in the evaluation of children's phobias, including the behavioral or problem-focused interview, the diagnostic interview, self-report inventories, caregiver completed instruments, behavioral observations, self-monitoring and physiological assessment. Reflecting recent theoretical and clinical advances in the study of childhood internalizing disorders, we also explore laboratory-based measures and family assessment measures. Particular attention is given to psychometric issues and developmental sensitivity in our discussion of these assessment procedures.     

Long-term perspective on the prevalent-cohort biases in studies of human immunodeficiency virus progression

Because considerable information about progression of human immunodeficiency virus (HIV) infection has been provided by studies of cohorts of individuals with prevalent HIV infection, this study was designed to investigate bias due to onset confounding (differential time-since-infection distributions) and differential length-biased sampling in epidemiologic analyses of data from such cohorts. Subjects were participants in the Italian Seroconverters Study, a seroincident cohort of more than 1,200 adults seen at ambulatory care clinics in Italy, with observed HIV seroconversion in 1980-1988. Acquired immunodeficiency syndrome (AIDS) diagnoses, based on the 1987 Centers for Disease Control case definition, and mortality were ascertained through Italian national registries through 1994. To estimate bias in prevalent cohorts, a series of pseudoseroprevalent (PSP) cohorts were drawn by sampling, from among the total seroincident cohort, prevalent AIDS-free subjects in each calendar year. The relative AIDS risk associated with a given covariate was calculated in each PSP cohort and compared with the relative AIDS risk for that covariate in the seroincident cohort. Relative risks were estimated by both the ratio of AIDS incidence densities and the relative AIDS hazards from proportional hazards regression. Differential length bias was not evident, as assessed in the following way: Among 338 individuals with seroconversion dates in 1983-1986, the relative risk of AIDS for subjects born before 1951 compared with those born more recently was 1.67 (95% confidence interval (CI) 1.30-2.14). Although differential length-biased sampling was expected to bias this relative risk toward 1.0, the observed relative risk for earlier birth ranged from 1.79 to 2.86 in 1987-1992 PSP cohorts. Onset bias was observed: Among 644 subjects with seroconversion in 1980-1988, the AIDS relative risk for 1980-1985 seroconverters compared with 1986-1988 seroconverters was 1.09 (95% CI 0.76-1.55). Onset bias was seen in 1988-1990 PSP cohorts (relative risks for early seroconversion = 1.47, 1.46, and 1.34, respectively); in 1991-1992, relative risks were close to the expected value of 1.09, and CIs on relative risks from all PSP cohorts after 1989 included 1.0. Confounding attributable to differential length-biased sampling in prevalent cohorts does not necessarily bias estimates of the impact of covariates on rate of progression to AIDS. Bias can arise when a covariate suspected of affecting AIDS risk is closely linked to date of acquisition of HIV infection. However, onset bias appears to wane as subjects' dates of infection become more remote.     

Pigmentation of the rainbow trout (Oncorhynchus mykiss) with oil-extracted astaxanthin from the langostilla (Pleuroncodes planipes)

The purpose of this contribution is to inform about the activities of the local ethics commission established at one of our largest teaching (University) hospitals. In 1995 the following priorities were recognized: studying international ethical standards of research involving human subjects and strictly adhering to them; bilingual administrative agenda in Czech and English; enforcing the patients' rights in health care and emphasizing them in education of medics and other students of health related disciplines; stimulating effective communication between doctors, other health care workers and lay persons in the commission as well as between the members of the commission and authors of research projects applying for ethical evaluation. Since 1993 the commission has been revising and storing in the archives more than 600 research projects. In 1996, 181 new research projects were reviewed, which is 35% more than in 1995. Approval was granted in 154 cases (85.08%), 3 cases (1.66%) were rejected, 15 cases (8.29%) approved on condition of complying with the recommendations of the commission, 6 cases (3.31%) recommended for another commission, and in 3 cases reviewing the project was postponed for lack of necessary data. The members of the commission agree that the future activities should lead to forming a broader group of consultants of the commission and other professional and lay people interested in clinical ethics. According to their meaning, legislation concerning ethical commissions in the Czech Republic, including material and financial support and administrative help, is urgently needed.     

Effects of dietary saturated andtrans fatty acids on cholesteryl ester synthesis and hydrolysis in the testes of rats

Studies were made of the enzymic synthesis and hydrolysis of cholesteryl esters in rat testes. Weanling rats were fed for 14 weeks diets containing 5% by wt of hydrogenated coconut oil (HCO), a concentrate of ethyl elaidate and linolelaidate (TRANS), devoid of essential fatty acids (EFA), or safflower oil (SAFF). Cholesterol esterifying activity was localized in the soluble fraction, and cholesteryl ester hydrolase activity was distributed in both particulate and soluble fractions obtained from tissue homogenates. The optimum pH was 6.0 for esterification and 6.9–7.0 for hydrolysis. Neither esterifying nor hydrolytic activity was affected by freezing and thawing, but both reactions were inhibited by heat or sonication. The animals of both the HCO and TRANS groups had developed an EFA deficiency before they were sacrificed. The EFA deficiency produced upon feeding the HCO diet had no apparent effect on the synthesis and hydrolysis of cholesteryl esters in rat testes. The TRANS diet influenced the development of the testes as judged by their size, and cholesterol esterifying and cholesteryl ester hydrolyzing activities were suppressed in the testes of the animals of this group. A major difference in the effects of the HCO and TRANS diets on the lipids of the testes was the relatively minor amount of eicosatrienoic acid (20∶3) and the elevated level of docosapentaenoic acid (22∶5) in the cholesteryl esters of the testicular lipids of the TRANS group.     

Enthalpies of pyrolysis and oxidation of Athabasca oil sands

Thermal degradation of Athabasca oil sands, bitumen, and its fractions have been investigated in N₂and in air, at 25–600 °C and at pressures up to 6.9 MPa, using thermogravimetry (TG) and high pressure differential scanning calorimetry (PDSC). These conditions are likely to occur during in-situ recovery of bitumen by underground combustion processes. Two regions of weight loss are detected using both gases. The endothermic low temperature volatilization reactions (150–400 °C) absorbed +26 mJ mg^?1 for oil sand to +2319 mJ mg^?1 for medium oil. The heats of reaction for high-temperature cracking and volatilization reactions (400–550 °C) were similar. The heats of reaction for the low-temperature oxidation reactions (150–375 °C) were ?405 mJ mg^?1 for oil sand to ?30200mJ mg^?1 for medium oil. Values for the high-temperature oxidation reactions (400–550 °C) were slightly higher. Increasing the pressure of nitrogen and air caused an increase in the endothermicity and exothermicity of the respective reactions.     

Effect of long term ingestion of gum arabic on the adipose tissues of female mice

Abdominal obesity is the most prevalent manifestation of metabolic syndrome. The anti-obese effects of dietary fiber is generally accepted, but specifically the anti-obese properties of the dietary fiber, gum arabic (GA) has not been well studied. In this investigation, we offered GA to the female 90 days old mice in the form of drink (1% w/v) for 180 days. Such GA in drinking water reduced age-dependent fat deposition in the visceral adipose tissue and improved the gastrocnemius muscle reduction. This inhibition of fat deposition effect is due to the β3-adrenergic stimulation of adipocytes in which TNFα down-regulation is probably involved. Modification of large intestinal microflora, as evidenced by a modification of cecal short-chain fatty acid profile and of 16S rDNA profile, may contribute to such reduction in TNFα expression in the adipose tissues.     

Catalyst surface at a fractal of cost—a quest for optimal catalyst loading

Intuition tells us that any decrease in the catalytically active surface area should result in an equivalent decrease in the reaction yield and efficiency. Our findings counter this by showing that the active surface and hence the catalyst loading can be reduced drastically in the diffusion-limited heterogeneous reaction systems, while the conversion rate remains essentially unchanged by using fractals for spatial distribution of the catalyst load. The results of this study provide an unusual circumstance for optimal design of chemically active surfaces and can be used to drastically reduce cost of heterogeneous chemical and biological reactors, sensors, and electrodes of fuel cells. The proposed approach can be exploited to its fullest extent in chemical microsystems by utilizing the latest advances in our abilities to manipulate matter on the micro/nano scale.     

Protection of lyocell fibres against fibrillation; Mode of action of the cross-linking agent 2,4-dichloro-6-(β-sulphatoethylsulphonyl)anilino-s-triazine

2,4-Dichloro-6-(β-sulphatoethylsulphonyl)anilino- s -triazine is used as a cross-linking agent to improve the wet abrasion resistance of Lyocell fibres. The agent, which exhibits poor water solubility, is sold as an aqueous dispersion. During application to Lyocell in the presence of alkali, the agent enters a solution phase before reacting with the fibres. High pressure liquid chromatography analysis and solution studies support the view that the two electrophilic species taking part in the cross-linking reaction are vinylsulphone plus one of the chlorine atoms of the dichlorotriazine residue and that preliminary hydrolysis of one of the chlorine atoms is not the cause of the observed solubility changes.