The tetravalent guanylhydrazone CNI-1493 blocks the toxic effects of interleukin-2 without diminishing antitumor efficacy

The use of interleukin 2 (IL-2) as an antineoplastic agent has been limited by the serious toxicities that accompany the doses necessary for a tumor response. Elevation of nitric oxide (NO) and tumor necrosis factor (TNF) both have been implicated in IL-2 toxicities. CNI-1493, a tetravalent guanylhydrazone, is an inhibitor of macrophage activation including the synthesis of TNF and other cytokines. Doses of CNI-1493 as low as 1 mg/kg/day conferred complete protection against fatal toxicity of IL-2 with IL-2 doses tenfold higher than the safely tolerated level in Sprague-Dawley rats. Moreover, typical pathologic changes in the lungs, kidneys, and the liver caused by IL-2 infusion were blocked by cotreatment with CNI-1493. When animals bearing established hepatomas were given IL-2 and CNI-1493 combination therapy, 10 of 10 hepatomas regressed from 1 cm3 to <1 mm3. Intracytoplasmic TNF levels were increased in normal tissues from IL-2 treated animals, and treatment with CNI-1493 maintained TNF at control levels. The degree of apoptosis measured by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining of tumors following IL-2 therapy was not reduced compared with IL-2 cotreated with CNI-1493. In contrast, apoptosis in the liver and lung parenchyma following IL-2 therapy was blocked completely by cotreatment with CNI-1493. Taken together, these data showed that low and infrequent doses of CNI-1493 markedly protected animals from IL-2 systemic toxicities whereas not affecting tumor response to IL-2 therapy. With the protection afforded by CNI-1493 treatment, IL-2 therapy dose levels could be increased to provide significant antitumor effects in animals with established hepatomas.     

Development, behaviour and temperament: a prospective study of infants conceived through in-vitro fertilization

The development, behaviour and temperament of 65 singleton infants conceived through in-vitro fertilization (IVF) and 63 matched controls were compared at 1 year postpartum. Primiparous women were recruited during pregnancy and their infants' development was assessed at 1 year. In addition, test-taking behaviour was evaluated by an examiner using the Bayley behaviour rating scale and mothers completed a behaviour problem checklist and temperament scale. Mental, motor, speech and social development were appropriate for age, with no significant group differences. While receptive language development was in the normal range, IVF infants scored lower than control infants. Across both groups, mothers reported low levels of behaviour difficulty and mean temperament ratings were in the general population range. There were no group differences in observed test-taking behaviour. However, IVF mothers rated their children at a higher level of behaviour difficulty and more reactive than the ratings given by control mothers. Overall, singleton children conceived through IVF demonstrate appropriate general development at 1 year of age. The higher reported behaviour difficulty experienced by IVF mothers may reflect their concerns about the well-being and adjustment of their child during the first year.     

Relationship of immune response to heat-shock protein A and characteristics of Helicobacter pylori-infected patients

This study assessed the minimum dose of clonidine required to prolong the duration of both anesthesia and analgesia after axillary brachial plexus blockade. Eighty patients scheduled for elective hand surgery were divided into eight groups in a randomized, double-blind fashion. An axillary brachial plexus block was performed with 40 mL 1% mepivacaine plus 1:200,000 epinephrine. The control group received no clonidine. In the other groups, increasing doses of clonidine (0.1, 0.2, 0.3, 0.4, 0.5, 1, and 1.5 micrograms/kg) were added to the local anesthetic solution. Onset time, duration of anesthesia and analgesia, postoperative pain score, intake of analgesics, and adverse effects were recorded. The eight groups were comparable in terms of onset time, postoperative pain score, and analgesic requirement. The minimum dose of clonidine required to significantly prolong the duration of analgesia and anesthesia was, respectively, 0.1 and 0.5 microgram/kg. No side effects (sedation, drowsiness, bradycardia, arterial hypotension) were reported. We conclude that the dose of clonidine required to prolong significantly the duration of both anesthesia and analgesia after axillary brachial plexus blockade is 0.5 microgram/kg and that, at this dose, clonidine may be used without important reported side effects even in outpatients.     

Immunology and disease control: a systems approach

The application of system theory (or more precisely, differential equations) to immunology and disease, in general, is presented here. Particular results from U.S.-Russian research collaboration depict the potential role of such systematic analysis for more effective health care and disease control. In particular, some emphasis is given to control of influenza. After a brief systematic overview of immunology, a simple infectious disease model is developed to explain four basic forms of disease: subclinical, acute, lethal and chronic. Then, disease treatment is studied.     

低阶煤中所含腐植酸的制备及应用

腐植酸(HA)主要存在于低阶煤(泥炭、褐煤和风化煤)之中,本文综述了从低阶煤中提取HA的几种工艺,并回顾了煤基HA在各行业的应用,最后对我国未来低阶煤和腐植酸行业进行了展望。     

The peculiarities of pigment-protein composition of intergranular thylakoid fragments from maize chloroplasts

The pigment-protein composition of two fractions of intergrana fragments from maize inbred lines F 7 and II 346 chloroplast had been investigated. It was shown that under electrophoretic separation of fraction 70,000 g from both lines and fraction 100,000 g from line F 7 the new band of pigment-protein complexes had been observed. It was determined that its polypeptide composition is the same as light-harvesting complex of PS II one, but it differs by low electrophoretical mobility. The conclusion was made that this is a new form of light-harvesting complex of PS II.     

Inducible nitric oxide synthase does not affect resolution of murine chlamydial genital tract infections or eradication of chlamydiae in primary murine cell culture

Mice lacking inducible nitric oxide synthase (iNOS) or treated with iNOS inhibitors resolved chlamydial genital tract infections. Additionally, treatment of primary murine cell cultures with gamma interferon restricted chlamydial growth in the absence of nitric oxide. From these results, iNOS activity is unnecessary for the resolution of chlamydial genital tract infections in mice and inhibition of chlamydial growth in culture.     

Pattern of cervical dilatation in previous lower segment caesarean section patients

The pattern of cervical dilatation during labour in 100 patients with previous lower segment caesarean section (LSCS) was determined in a prospective partographic study. Eighty-four subjects delivered successfully by vaginal route. The mean initial dilatation rate (IDR) and average dilatation rate (ADR) were 0.884 cm/hour and 1.255 cm/hour respectively. The mean IDR and ADR of the patients who delivered vaginally were 0.96 cm/hour and 1.41 cm/hour respectively, while of those who required repeat LSCS mean IDR was 0.44 cm/hour and mean ADR was 0.42 cm/hour. Hence ADR in cases who required repeat LSCS was significantly slower as compared to those who delivered vaginally (p < 0.01). Most (87.5%) of the cases who required repeat LSCS crossed the alert line as compared to 34.5% of patients who delivered vaginally. The mean admission delivery interval (ADI) was 9.45 +/- 4.29 hours in patients with no previous vaginal delivery and 8.02 +/- 4.83 hours in patients with previous vaginal delivery. The mean durations of 1st and 2nd stages of labour were 11.8 +/- 5.35 hours and 29.4 +/- 27.3 minutes respectively. It is concluded that partographic evaluation is an important aspect in management of labour of such patients.