Reduction of adhesion formation in rabbits by intraperitoneal administration of lazaroid formulations

Adhesion formation is a major source of postoperative morbidity and mortality. In this study, the ability of a variety of lazaroid formulations [the antioxidant 21-aminosteroid PNU74006F (tirilazad) and the non-steroidal 2-methylaminochroman derivative PNU83,836E] to reduce i.p. adhesion formation in three rabbit models was examined. In initial studies, PNU83836E was administered via Alzet miniosmotic pump to the site of injury. In the sidewall and double uterine horn models, PNU83,836E was administered via Alzet miniosmotic pump for the entire postoperative interval. In the sidewall model, there was a dose- dependent reduction in the area of the sidewall injury that was involved in adhesions. In the double uterine horn model, PNU83,836E was administered via Alzet miniosmotic pump to the area of injury for 1, 2, 3 or 7 days. Administration for as little as 24 h after surgery significantly reduced the extent of adhesion formation and the reduction was increased if it was administered for longer. Further studies were conducted in which various lazaroid formulations were administered as a bolus at the end of surgery. In both the sidewall and double uterine horn models, administration of either PNU83,386E (in citrate buffer) or PNU74006F (in cyclodextrin or lipid emulsion vehicles) at the end of surgery reduced adhesion formation. Administration of a bolus of PNU74006F 10 min prior to initiation of surgery with or without additional treatment at the end of surgery further increased its efficacy in the reduction of adhesion formation. Administration of a minimum of 1.5 mg before and after surgery (3 mg total) was required for maximal efficacy. These studies demonstrate that pre- and postoperative administration of either a steroidal (PNU74006F) or non-steroidal (PNU83,836E) lazaroid intraperitoneally reduced the formation and reformation of postoperative adhesions in three animal models.      

Development and Evaluation of an Interactive CD-ROM Refusal Skills Program to Prevent Youth Substance Use: “Refuse to Use”

An interactive CD-ROM program designed to reduce adolescent substance use was developed and evaluated. The program uses video vignettes to teach refusal skills and socially acceptable responses to substance use situations, specifically offers of marijuana. In a randomized pretest-to-posttest experiment with 74 public school students from six classes in three high schools, significant changes were observed at posttest on (1) the adolescent's personal efficacy to refuse the offer of marijuana, (2) the adolescent's intention to refuse marijuana if offered, and (3) the adolescent's perceptions of the social norms associated with substance use and the importance of respecting another's decision to refuse a drug offer. In addition, adolescents in the treatment condition were able to recall approximately 50% of the portrayed refusal strategies. Findings are discussed with regard to the potential benefits of an interactive multimedia approach for conducting substance use interventions.     

Rotavirus survival on human hands and transfer of infectious virus to animate and nonporous inanimate surfaces.

We tested the survival of the Wa strain of human rotavirus on the hands of volunteers and also studied infectious virus transfer between animate and inanimate (stainless steel disks) surfaces. The virus was diluted in a 10% suspension of feces, and 10 microliters (1 X 10(3) to 4 X 10(4) PFU) was placed on each of the four fingerpads of the left hand. One milliliter of 20% tryptose phosphate broth in Earle balanced salt solution was used for virus elution from each fingerpad, and the hands were disinfected with 70% ethanol before they were washed with an antiseptic soap and water. At 20, 60, and 260 min after inoculation, approximately 57, 43, and 7%, respectively, of the input infectious virus could be recovered. For virus transfer, the inoculum (2 X 10(4) to 8 X 10(4) PFU) was allowed to dry, and the donor surface was kept in contact with the recipient surface for 10 s at a pressure of approximately 1 kg/cm2. At 20 and 60 min after virus inoculation, 16.1 and 1.8%, respectively, of the input infectious virus could be transferred from the contaminated hand to a clean disk; when a clean hand was pressed against a contaminated disk, virus transfer was 16.8 and 1.6%, respectively. Contact between a contaminated and a clean hand 20 and 60 min after virus inoculation resulted in the transfer of 6.6 and 2.8%, respectively, of the input infectious virus. These findings indicate the potential vehicular role for human hands in the spread of rotaviral infections.     

Exotoxin activity associated with the Legionnaires disease bacterium.

Hemolysis occurred around growth of the Legionnaires disease bacterium on supplemented Mueller-Hinton agar containing sterile defibrinated blood from each of five mammalian species. Hemolysis was most pronounced with guinea pig or rabbit blood, was less intense with horse or sheep blood, and was slight with blood from a human donor. Sterile filtrates of allantoic fluid from embryonated hen's eggs that had been infected with this organism displayed hemolytic activity in a radial hemolysis assay with guinea pig cells in agar. Growth of the Legionnaires disease bacterium on F-G agar with 5% hen's egg yolk was surrounded by a zone of clearing and more circumscribed zones of iridescence and increased opacity on and in the medium. Attempts to detect activity analogous to that of Escherichia coli heat-labile or heat-stable enterotoxin in allantoic fluid from infected eggs or in cultures of the Legionnaires disease bacterium were not successful.     

Effect of pituitary gonadotrophins on proliferation of primary cultures of human ovarian stroma

Proliferation of ovarian stromal cells is a common phenomenon in peri- and post-menopausal ovaries. It is generally assumed to be secondary to the rise in circulating gonadotrophins at the menopause, though the process by which it occurs is poorly understood. This study aimed to examine the effect of menopausal levels of pituitary gonadotrophins on the growth of primary cultures of ovarian stroma. A culture system was developed using primary explants of ovarian stroma on a collagen substrate. The effect of follicle stimulating hormone (FSH; 10(-5) g/l) and luteinizing hormone (LH; 10(-5) g/l) on the proliferation of cultures derived from the cortices and medullae of ten ovaries was evaluated using a dual radiothymidine labelling technique. FSH was stimulatory to cortical cultures from 9/10 ovaries and medullary cultures from 7/10 ovaries, while LH was stimulatory to cortical cultures from 6/9 ovaries and medullary cultures from 5/10 ovaries. The responsiveness of the cultures did not correlate with the degree of hyperplasia in vivo. This study demonstrates that pituitary gonadotrophins may modulate the growth of stromal cells in culture, and thus may play a role in the process whereby stromal proliferation occurs in peri- and post-menopausal ovaries.     

Evidence for the phagocytic transport of intestinal particles in dogs and rats.

Fluorescent latex beads of two different colors were implanted into separate intestinal segments in individual dogs and rats. Mesenteric lymph node phagocytes subsequently contained multiple beads of one or the other color but rarely both colors, indicating that intestinal phagocytes transported the latex beads to the draining lymph node. Fluorescent labeled Escherichia coli was implanted into rat ligated intestinal segments, and rare mesenteric lymph node phagocytes subsequently contained fluorescent bacteria, suggesting that intestinal bacteria might be transported in the same manner as inert latex beads.     

难治性便秘综合治疗及影响因素的评价

目的评价综合治疗对难治性便秘的疗效及影响因素。方法将84例难治性便秘分为非重叠组和重叠组。应用个体化综合治疗4周,观察便秘症状评分变化及总有效率,分析IC患者的重叠症状和心理障碍状态对疗效的影响。结果(1)84例便秘患者中,重叠组和非重叠组分别占40.5%和59.5%。(2)重叠组和非重叠组的总有效率分别为50.0%和78.0%(P<0.05)。(3)对37例IC患者的心理测试调查显示,59.4%(22/37)有心理障碍状态,重叠组和非重叠组伴有心理障碍状态对治疗的总有效率分别为4.8%和31.5%(P<0.05)。结论适合个体化的综合治疗使多数难治性便秘缓解症状,但伴有重叠症状,尤其心理障碍状态则影响疗效。     

Epitope mapping of a protective monoclonal antibody against Pneumocystis carinii with shared reactivity to Streptococcus pneumoniae surface antigen PspA

Pneumocystis carinii is an opportunistic fungal pathogen that causes pneumonia in the immunocompromised host. A protective monoclonal antibody (MAb) termed 4F11 generated against mouse-derived P. carinii was shown by indirect immunofluorescence assay (IFA) to bind surface antigens of P. carinii derived from multiple host species, including humans. We have identified multiple epitopes recognized by MAb 4F11 in two recombinant mouse P. carinii antigens. The epitopes mapped have similar proline content and positive charge distribution. The consensus 8-mer epitope recognized by MAb 4F11 is K/RPA/RPK/QPA/TP. Immune sera raised against intact mouse P. carinii recognized native antigens affinity purified with MAb 4F11 and a recombinant antigen reactive with MAb 4F11. Database searches for short, nearly exact matches to the mapped MAb 4F11 epitopes identified a bacterial surface antigen, Streptococcus pneumoniae PspA, with a similar proline-rich region. In an IFA, MAb 4F11 detected antigens on the S. pneumoniae surface, and Western blotting identified a protein in S. pneumoniae lysates consistent with the M(r) of PspA. A fragment of the S. pneumoniae PspA gene was cloned and sequenced, and the deduced amino acid sequence contained a region with strong similarity to the MAb 4F11 epitopes identified in P. carinii. The PspA recombinant polypeptide was recognized by MAb 4F11 in a Western blot. The ability of MAb 4F11 to recognize similar proline-rich epitopes may explain its ability to recognize P. carinii derived from multiple hosts and will permit testing of the epitopes recognized by this antibody in immunization against P. carinii.