Reimagine: a randomized controlled trial of an online, symptom self-management curriculum among breast cancer survivors.

PURPOSE: Chronic pain, depression, and fatigue are common effects resulting from the cancer experience; new interventions are needed. This study examined the effect of Reimagine, an online symptom self-management curriculum that teaches coping skills, on key outcomes. METHODS: Adult breast cancer survivors with chronic pain were recruited from the Army of Women volunteer registry for this randomized controlled trial and randomized 1:1 to Reimagine or usual care conditions. Electronic surveys collected demographic, clinical, and outcome data at baseline and 18 weeks post-intervention. RESULTS: Participants (N = 89) were mean age 56.7 ± 8.7 years; 67% married; 58% employed; mean years since diagnosis 8.2 ± 6.6; and 89% were in remission or cured of their breast cancer. There was a significant difference in the change in depression scores for treatment (M = - 1.7, SD = 4.5) and usual care (M = 0.3, SD = 3.8) conditions; t(85) = - 2.3, p = .03. Difference in the change in fatigue scores was significant for treatment (M = 4.8, SD = 9.0) and usual care (M = 1.2, SD = 6.6) conditions; t(87) = 2.2, p = .03. Most Reimagine users (94%) would recommend the curriculum to others. CONCLUSIONS: These results suggest that Reimagine has an effect on depression and fatigue symptoms for breast cancer survivors. Online programs can be a feasible and effective alternative to in-person support. Additional research is recommended with larger and more diverse samples.

Sociodemographic, psychosocial and clinical factors associated with uptake of genetic counselling for hereditary cancer: a systematic review.

Evidence suggests that a significant proportion of individuals referred to cancer genetic counselling (GC) do not attend, and thus may not be engaged in adequate cancer risk management. We aimed to review the literature to better understand barriers to accessing GC and how they may be overcome. We conducted a systematic literature search for articles examining factors influencing cancer GC uptake as well as motivators and barriers to GC attendance. Factors were categorised as sociodemographic, psychosocial or clinical. The literature search identified 1413 citations, 35 of which met the inclusion criteria. GC uptake ranged from 19% to 88%. With the exceptions of education level, socioeconomic status, cancer-specific distress, personal cancer diagnosis and actual and perceived risk of cancer, support was lacking for most sociodemographic, clinical and psychosocial factors as predictors of GC uptake. Cost and logistical barriers, emotional concerns, family concerns and low perceived personal relevance were reported as important considerations for those declining GC. We conclude that there is poor understanding of GC and a lack of decision support among those referred to GC. Research into ways of providing education and support to referred individuals will be important as the scope and availability of GC and genetic testing broaden.

Radiation therapy for people with cancer: what do written information materials tell them?

This study aimed to compare and contrast the contents of different types of written patient information about radiotherapy, namely (1) hospital radiotherapy departments vs. cancer control organisations and (2) generic vs. tumour-specific materials. A coding framework, informed by existing patients' information needs literature, was developed and applied to 54 radiotherapy information resources. The framework comprised 12 broad themes; cancer diagnosis, general information about radiotherapy, treatment planning, daily treatment, side effects, self-care management, external radiotherapy, internal radiotherapy, impact on daily activities, post-treatment, psychosocial health and other content, such as a glossary. Materials produced by cancer organisations contained significantly more information than hospital resources on diagnosis, general radiotherapy information, internal radiotherapy and psychosocial health. However, hospital materials provided more information about treatment planning, daily treatment and the impact on daily activities. Compared to generic materials, tumour-specific resources were superior in providing information about diagnosis, daily treatment, side effects, post-treatment and psychosocial health. Information about internal radiotherapy, prognosis and chronic side effects were poorly covered by most resources. Collectively, hospital and cancer organisation resources complement each other in meeting patients' information needs. Identifying ways to consolidate different information sources could help comprehensively address patients' medical and psychosocial information needs about radiotherapy.

Vaccinations in sickle cell disease: An audit of vaccination uptake in sickle cell patients attending Newham University Hospital.

AIMS: To assess the level of adherence of patients with sickle cell disease to the advised vaccination schedule with respect to the Sickle Cell Society guidelines on vaccination [1,2]. METHODS: A retrospective audit of patients' vaccination records was carried out between July 2012 and June 2013 on a sample of 80 patients over the age of 16, who attended Newham University Hospital accident and emergency (A&E) department with a presenting complaint coded as "sickle cell". A re-audit was conducted from January 2014 to December 2014 to close the audit loop. Chi-squared and Fisher's exact tests were used to compare the results. RESULTS: The initial audit and re-audit identified 80 and 86 patients, respectively. Only 2 (2012-2013) and 7 (2014) patients had a complete up-to-date vaccination profile. 24 (30%) patients had up-to-date influenza vaccination, increasing to 43 (50%, P=0.0062) when re-audited. 33 (41%) had current pneumococcal vaccinations, increasing to 38 (44%, P=0.7874). Uptake rates for vaccinations against Meningococcal group C (MenC), Haemophilus influenzae B (HiB) and Hepatitis B virus (HBV) were under 31% in both audits. A significant improvement in vaccination rate was observed for all vaccinations except pneumococcal and HBV. CONCLUSIONS: Although significant improvements have been demonstrated, this audit shows a low level of adherence to the advised vaccination schedule. The study also highlighted a shortfall in appropriate record keeping, reducing the potential for detailed conclusions being drawn in relation to the childhood vaccinations against MenC, HiB and HBV. Implementation of a new database of vaccination history, raising GP awareness and patient education seminars has lead to a significant improvement in vaccination rates locally and the authors hope that this may be replicated in other centres. There may be potential to increase rates further by administering vaccinations to inpatients.

Are radiation oncologists aware of health literacy among people with cancer treated with radiotherapy?

Health literacy skills are important for people affected by cancer as they are exposed to complex treatment and follow-up care information. This study aimed to (1) explore radiation oncologists' understandings and awareness of health literacy among patients with a reasonable command of English; (2) gain insight into oncologists' views regarding health literacy; and (3) identify techniques oncologists employ to communicate to different literacy populations. We conducted semi-structured interviews with 26 radiation oncologists. Four key themes were identified: (1) identifying a patient's literacy level; (2) perceived impact of literacy; (3) challenges and strategies to communicating concepts and supporting decision-making; and (4) suggested improvements to the health system. Participants described subjectively assessing a person's literacy level by monitoring the types of questions asked; analysing the language used; examining non-verbal behaviour, and considering a person's socio-economic situation. Participants reported the challenges of discussing the subtleties of cancer treatments with lower literacy groups such as the benefits and risks of treatment options and clinical trials, and tended to provide the basic facts to facilitate understanding. Radiation oncologists acknowledged the importance of health literacy in oncology, and employed a number of techniques to tailor their communication to different literacy populations. Further research is needed to address the challenges faced by oncologists when interacting with different literacy groups.

Establishment of the black-tailed prairie dog (Cynomys ludovicianus) as a novel animal model for comparing smallpox vaccines administered preexposure in both high- and low-dose monkeypox virus challenges.

The 2003 monkeypox virus (MPXV) outbreak and subsequent laboratory studies demonstrated that the black-tailed prairie dog is susceptible to MPXV infection and that the ensuing rash illness is similar to human systemic orthopoxvirus (OPXV) infection, including a 7- to 9-day incubation period and, likely, in some cases a respiratory route of infection; these features distinguish this model from others. The need for safe and efficacious vaccines for OPVX in areas where it is endemic or epidemic is important to protect an increasingly OPXV-naïve population. In this study, we tested current and investigational smallpox vaccines for safety, induction of anti-OPXV antibodies, and protection against mortality and morbidity in two MPXV challenges. None of the smallpox vaccines caused illness in this model, and all vaccinated animals showed anti-OPXV antibody responses and neutralizing antibody. We tested vaccine efficacy by challenging the animals with 10(5) or 10(6) PFU Congo Basin MPXV 30 days postvaccination and evaluating morbidity and mortality. Our results demonstrated that vaccination with either Dryvax or Acambis2000 protected the animals from death with no rash illness. Vaccination with IMVAMUNE also protected the animals from death, albeit with (modified) rash illness. Based on the results of this study, we believe prairie dogs offer a novel and potentially useful small animal model for the safety and efficacy testing of smallpox vaccines in pre- and postexposure vaccine testing, which is important for public health planning.

Teladorsagia circumcincta: activation-associated secreted proteins in excretory/secretory products of fourth stage larvae are targets of early IgA responses in infected sheep.

A detailed proteomic analysis of excreted/secretory (ES) proteins derived from fourth stage larvae (L4) of Teladorsagia circumcincta identified a number of components, including N-type and C-type single domain activation-associated secreted proteins (ASPs). Immunoblotting of L4 ES extracts with abomasal mucus derived from infected, immune sheep demonstrated the immunogenicity of some of these components, including an N-type single-domain ASP, designated Tci-ASP-1. The full-length cDNA encoding this protein was isolated and sequenced. Homology searches using the inferred amino acid sequence of Tci-ASP-1 showed that it had highest identity (75% over 231 residues) to, a N-type, single-domain ASP from Ostertagia ostertagi. Phylogenetic analysis confirmed the relationship of Tci-ASP-1 with other N-type ASPs. Reverse-transcriptase (RT)-PCR experiments demonstrated the presence of transcript encoding Tci-ASP-1 in L4 and adult stage T. circumcincta but not in pre-parasitic stages such as eggs and third stage larvae. A recombinant version of Tci-ASP-1 was expressed in Escherichia coli and the purified protein was reactive with IgA present in abomasal mucus derived from immune sheep.

Effect of low-dose mifepristone administration on day 2 after ovulation on transcript profiles in implantation-stage endometrium of rhesus monkeys.

Progesterone is essential for endometrial receptivity in primates. In studies previously performed using global gene profiling based on microarray technology, attempts have been made to identify changes in gene expression between early luteal-phase and mid-luteal-phase endometria. However, the issue of the putative impact of preimplantation embryo-derived signal in the process of endometrial receptivity was missing in the previous studies. In the present study, an attempt has been made to delineate the transcripts profile in implantation-stage endometrium under combinatorial regulation of progesterone and embryo-derived signal in the rhesus monkey. To this effect, we have compared transcript profiles for 409 known genes between control receptive stage (n=13), and mifepristone-induced desynchronized and non-receptive stage (n=12) monkey endometrial samples collected on days 4 (n=12) and 6 (n=13) after ovulation from mated, potential conception cycles, using cDNA arrays containing sequence-verified clones. Statistical analysis of correlation of estimated transcript abundance between arrays and qRT-PCR for nine selected gene products yielded significant (P<0.05) concordance. Of 409 genes, a total of 40 gene transcripts were seen to be affected, nine gene transcripts in endometrial samples were found to progressively increase between days 4 and 6 following mifepristone treatment, while an additional five genes showed differential expression profile depending on the day after treatment. Additionally, different sets of 12 and 14 gene products showed changes in days 4 and 6 post-ovulation samples respectively. A new cohort of 28 gene products in implantation-stage endometrium was seen to be affected by luteal-phase mifepristone.

Proteomic analysis of excretory/secretory products released by Teladorsagia circumcincta larvae early post-infection.

Teladorsagia circumcincta is an important parasitic nematode of domestic small ruminants. Drug resistance in this species is common so alternative methods of control are required. As animals develop immunity to T. circumcincta, vaccination is a valid option. Little is known about the antigens that play a role in stimulating immunity at this host/parasite interface. As responses generated between 1 and 5 dpi are known to affect development of these nematodes in their gastric niche, we focused on proteins released during the early stages of infection. To identify molecules potentially involved in immunity, we undertook a proteomics analysis of proteins released from larvae harvested at 1-, 3- and 5-days post-infection (dpi). This analysis produced peptide sequence data that was used to search information available in T. circumcincta expressed sequence tag (EST) databases and enabled identification of a number of excretory/secretory (ES) proteins. Immunoblots were performed to assess the relative molecular weight of ES antigens that were targets of local IgA responses in mucus from sheep rendered immune to infection. ELISA was performed to assess antigen-specific mucus IgA levels in individual sheep. These experiments provided preliminary evidence that the proteins identified in the larval secretome were subject to these antibody responses.

Immune recognition of the surface associated antigen, Tc-SAA-1, from infective larvae of Teladorsagia circumcincta.

A cDNA encoding a surface-associated antigen was amplified by reverse transcriptase polymerase chain reaction (PCR) from RNA extracted from Teladorsagia circumcincta exsheathed third stage larvae (xL3). The protein encoded by this cDNA, Tc-SAA-1, displays 77% identity over 162 amino acid residues to a surface associated antigen from Ancylostoma caninum (Ac-SAA-1). Antiserum raised against a bacterially-expressed recombinant form of Tc-SAA-1 reacted with a native protein in somatic and surface extracts of xL3 but not with L4 or adult parasites. Limited binding of anti-Tc-SAA-1 antibody was observed on the cuticular surface of xL3 s, however, regions of localization underlying the cuticle were observed. Incubation of xL3 T. circumcincta with anti-SAA rabbit serum failed to significantly inhibit penetration of the abomasal mucosa in vitro. IgA in abomasal mucus derived from sheep that had received a trickle infection of T. circumcincta bound recombinant Tc-SAA-1.

Immunoneutralization of vascular endothelial growth factor inhibits pregnancy establishment in the rhesus monkey (Macaca mulatta).

Maternal endometrial vascular endothelial growth factor (VEGF) is considered important in blastocyst implantation. However, there is no direct evidence to support this conjecture in the primate. In the present study, we have examined this hypothesis by testing whether immunoneutralization of VEGF during the peri-implantation stage of gestation affects embryo implantation in the rhesus monkey. Adult female animals (n = 36) during mated ovulatory cycles were randomly assigned to one of the experimental groups treated subcutaneously with either isotype-matched mouse immunoglobulin (group 1: control, n = 8) or monoclonal mouse antibody against VEGF-A (anti-VEGF Mab; group 2: 10 mg on day 5 after ovulation, n = 8; group 3: 20 mg on day 5 after ovulation, n = 8; group 4: 10 mg on day 10 after ovulation, n = 4; group 5: 10 mg on days 5 and 10 after ovulation, n = 8). Anti-VEGF Mab-treated animals in groups 2-4 did not show any marked inhibition in pregnancy establishment. On pooled analysis, however, anti-VEGF Mab administration in groups 2-5 (n = 28) resulted in a significant (P < 0.04) decline in the number of viable term pregnancy when compared with control animals. The observed difference was explained by the fact that 10 mg anti-VEGF Mab given to each animal on days 5 and 10 after ovulation in group 5 (n = 8) inhibited pregnancy establishment significantly (P < 0.02) when compared with control group 1. There was no significant change in serum concentrations of estradiol-17beta, progesterone, and free VEGF among groups. Furthermore, animals treated with anti-VEGF Mab (n = 8) as in group 5 revealed marked decrease in immunoreactive VEGF, fms-like tyrosine kinase-1, and kinase-insert domain region in trophoblast cells associated with shallow uterine invasion on day 13 of gestation when compared with samples from control group animals (n = 8). Thus, VEGF action is required for successful blastocyst implantation in the rhesus monkey.

Parasite loss and inhibited development of Teladorsagia circumcincta in relation to the kinetics of the local IgA response in sheep.

Groups of yearling sheep, which had been trickle infected with Teladorsagia circumcincta for 8 weeks and then drenched, were challenged with 50 000 T. circumcincta larvae together with groups of worm-free controls. Fewer parasites and a greater proportion of early fourth stage larvae were recovered from previously infected sheep compared to controls. Worm loss and arrested development were evident by 5 days after challenge whereas growth retardation of developing worms was observed by day 10. In the previously infected sheep a secondary IgA response was observed in the efferent gastric lymph from 5 days post-infection. Western blot analysis showed the lymph IgA to be predominantly dimeric and nonsecretory in nature and that the somatic antigens recognized were predominantly in the 100-250 kDa range. The concentration of IgA in lymph was always higher than in blood and in the previously infected sheep increased fivefold 8 days post-challenge in contrast to blood where IgA levels were unchanged. The timing of the response suggested that it occurred too late to have been the cause of worm loss or arrested development, though it may have retarded the growth of developing parasites.

WITHDRAWN: Gonadotrophin-releasing hormone analogues for pain associated with endometriosis.

BACKGROUND: Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is unclear but it is evident that endometriosis arises by the dissemination of endometrium to ectopic sites and the subsequent establishment of deposits of ectopic endometrium. The observation that endometriosis is rarely seen in the hypo-oestrogenic (low levels of oestrogen) post-menopausal woman led to the concept of medical treatment by induction of a pseudo-menopause using Gonadotrophin Releasing Hormone Analogues (GnRHas). When administered in a non-pulsatile manner (the pituitary is normally stimulated by pulses of natural GnRH and all analogues act on the pituitary at a constant level) their use results in down regulation (switching off) of the pituitary and a hypogonadotrophic hypogonadal state (low levels of female hormones due to non stimulation of the ovary). OBJECTIVES: To determine the effectiveness of Gonadotrophin Releasing Hormone analogues (GnRHas) in the treatment of the painful symptoms of endometriosis by comparing them with no treatment, placebo, other recognised medical treatments, and surgical interventions. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group (please see Review Group details) was used to identify all randomised trials of the use of GnRHas for the treatment of the painful symptoms of endometriosis. SELECTION CRITERIA: Trials were included if they were randomised, and considered the effectiveness of GnRHas in the treatment of the painful symptoms of endometriosis. DATA COLLECTION AND ANALYSIS: Twenty-six studies had data appropriate for inclusion in the review. The largest group (15 studies) compared GnRHas with danazol. There are five studies comparing GnRHas with GnRHas plus add-back therapy, three comparing GnRHa with GnRHa in a different form or dose, one compares them with gestrinone, one with the combined oral contraceptive pill, and one with placebo. Data was extracted independently by two reviewers. The authors of eleven studies have been contacted to clarify missing or unclear data. Only four have replied to date. Data on relief of pain, change in revised American Fertility Society (rAFS) scores, and side effects was collected. MAIN RESULTS: No difference was found between GnRHas and any of the other active comparators with respect to pain relief or reduction in endometriotic deposits. The side effect profiles of the different treatments were different, with danazol and gestrinone having more androgenic side effects, while GnRHas tend to produce more hypo-oestrogenic symptoms. AUTHORS' CONCLUSIONS: There is little or no difference in the effectiveness of GnRHas in comparison with other medical treatments for endometriosis. GnRHas do appear to be an effective treatment. Differences that do exist relate to side effect profiles. Side effects of GnRHas can be ameliorated by the addition of addback therapy.

Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium.

In women, a single dose of the antiprogestin mifepristone (RU486) in the secretory phase rapidly renders the endometrium unreceptive and is followed by endometrial breakdown and menstruation within 72 h. This model provides a system to identify progesterone-regulated genes, which may be involved in endometrial receptivity and the induction of menstruation. We used cDNA microarrays to monitor the response of the endometriuim over 24 h following administration of mifepristone in the mid-secretory phase. We identified 571 transcripts whose expression was significantly altered, representing 131 biochemical pathways. These include new progesterone regulated members of the Wnt, matrix metalloproteinase (MMP), prostaglandin (PG) and chemokine regulatory pathways. Transcripts involved in thyroid hormone metabolism and signalling such as type II iodothyronine deiodinase and thyroid receptors were also found to be highly regulated by progesterone antagonism in the endometrium. Transcripts required for thyroid hormone synthesis such as thyroid peroxidase (TPO) and thyroglobulin (TG) were also expressed, indicating that the endometrium may be a site of thyroxin production. These results add to the existing knowledge of the role of the Wnt, chemokine, MMP and PG pathways in receptivity and early menstrual events. They provide in vivo evidence supporting direct or indirect regulation of many new transcripts by progesterone. We have also identified for the first time the very early transcriptional changes in vivo in response to progesterone withdrawal. This greatly increases our understanding of the pathways leading to menstruation and may provide new approaches to diagnose and treat menstrual disorders.

Evaluation of broad-spectrum anthelmintic activity in a novel assay against Haemonchus contortus, Trichostrongylus colubriformis and T. sigmodontis in the gerbil Meriones unguiculatus.

The gerbil Meriones unguiculatus, infected with three species of nematodes, each located in a separate part of the gastrointestinal tract, provided a reliable laboratory assay for the evaluation of broad-spectrum anthelmintic activity. Gerbils harbouring 6-day-old infections of Haemonchus contortus, Trichostrongylus colubriformis and T. sigmodontis were given selected broad-spectrum anthelmintics by gavage. Three benzimidazoles, thiabendazole, oxfendazole and albendazole, a tetrahydropyrimidine, morantel, an imidazothiazole, levamisole hydrochloride, a macrocyclic lactone, ivermectin and an experimental natural product, paraherquamide, were active against all three nematodes at various dosages. Trichostrongylus colubriformis was most sensitive to levamisole hydrochloride, morantel, thiabendazole and paraherquamide whereas ivermectin, oxfendazole and albendazole were more effective against H. contortus. All compounds were active against the caecal nematode T. sigmodontis although it was less sensitive than T. colubriformis. Haemonchus contortus was more sensitive than T. sigmodontis to all anthelmintics tested except thiabendazole.

Molecular characterization of a family of metalloendopeptidases from the intestinal brush border of Haemonchus contortus.

Substantial protection against the economically important parasitic nematode Haemonchus contortus has been achieved by immunizing sheep with a glycoprotein fraction isolated from the intestinal membranes of the worm (H-gal-GP). Previous studies showed that one of the major components of H-gal-GP is a family of at least 4 zinc metalloendopeptidases, designated MEPs 1-4. This paper describes aspects of the molecular architecture of this protease family, including the proteomic analysis of the MEP fraction of the H-gal-GP complex. These enzymes belong to the M13 zinc metalloendopeptidase family (EC 3.4.24.11), also known as neutral endopeptidases or neprilysins. The sequences of MEPs 1 and 3 suggested a typical Type II integral membrane protein structure, whilst MEPs 2 and 4 had putative cleavable signal peptides, typical of secreted proteins. Proteomic analysis of H-gal-GP indicated that the extracellular domain of all 4 MEPs had been cleaved close to the transmembrane region/signal peptide with additional cleavage sites mid-way along the polypeptide. MEP3 was present as a homo-dimer in H-gal-GP, whereas MEP1 or MEP2 formed hetero-dimers with MEP4. It was found that expression of MEP3 was confined to developing 4th-stage larvae and to adult worms, the stages of Haemonchus which feed on blood. MEP-like activity was detected in the H-gal-GP complex over a broad pH range (5-9). Since all 4 MEPs must share a similar microenvironment in the complex, this suggests that each might have a different substrate specificity.

An immunogenic cathepsin F secreted by the parasitic stages of Teladorsagia circumcincta.

Teladorsagia circumcincta is a common, pathogenic abomasal nematode of sheep. In order to improve disease control in parasite isolates resistant to several anthelmintics, alternative methods must be sought. Sheep develop acquired immunity to T. circumcincta so vaccination is a valid option for control. For this reason, we are investigating parasite excretory/secretory products for molecules, which have potential to invoke protective immunity against T. circumcincta. Here, we describe experiments in which we identified a novel, immunogenic cathepsin F secreted by L4 T. circumcincta. This protease, initially identified by mass spectrometry analysis, is the most abundant molecule in excretory/secretory products released in vitro by T. circumcincta harvested at 5, 6 or 9 days p.i. and is a target of specific, local IgA responses in sheep which are immune to challenge infection. The full-length cDNA encoding this secreted protease was isolated. Sequence and phylogenetic analyses indicated that the protease (designated T. circumcincta cathepsin F-1, Tci-CF-1) belongs to the cathepsin F class and exhibits greatest identity (>60%) to expressed sequence tags present in the Ostertagia ostertagi and Haemonchus contortus expressed sequence tag databases. Tci-CF-1 also displays high identity to hypothetical proteins identified in the genomes of Caenorhabditis elegans and Caenorhabditis briggsae, both proteins having been described as cathepsin F enzymes. Specific inhibitor binding assay of larval excretory/secretory products confirmed the classification of this excretory/secretory component as a cathepsin F. Reverse transcription-PCR studies indicated that Tci-cf-1 is developmentally regulated and is particular to the host parasitic stages of T. circumcincta. The abundance, immunogenicity and temporal expression pattern of Tci-CF-1 make this a potential vaccine candidate for teladorsagiosis.

Protection induced by vaccinating sheep with a thiol-binding extract of Haemonchus contortus membranes is associated with its protease components.

Previous work has shown that a protein extract enriched for cysteine protease activity (TSBP) prepared from adult Haemonchus contortus using thiol sepharose affinity chromatography confers substantial protection against a single challenge infection. TSBP comprised proteases and other proteins. Here, TSBP were further fractionated using anion-exchange chromatography and fractions pooled on the basis of containing (1) protease activity, (2) a prominent non-protease peptide and (3) material which did not bind to the column. A protection trial showed that only the protease-enriched material conferred protective immunity and this was comparable to that observed in a TSBP-immunized positive control group. Immunization stimulated a marked IgG response with the IgG2 isotype predominating.

Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis.

BACKGROUND: Women with endometriosis have elevated levels of cyclooxygenase-2 (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2 has been shown to reduce inflammation, angiogenesis and cellular proliferation. It may also downregulate aromatase activity in ectopic endometrial lesions. Ectopic endometrial establishment and growth are therefore likely to be suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2 inhibition would reduce the size and number of ectopic human endometrial lesions in a nude mouse model of endometriosis. METHODS: The selective COX-2 inhibitor, nimesulide, was administered to estrogen-supplemented nude mice implanted with human endometrial tissue. Ten days after implantation, the number and size of ectopic endometrial lesions were evaluated and compared with lesions from a control group. Immunohistochemical assessment of vascular development and macrophage and myofibroblast infiltration in control and treated lesions was performed. RESULTS: There was no difference in the number or size of ectopic endometrial lesions in control and nimesulide-treated nude mice. Nimesulide did not induce a visually identifiable difference in blood vessel development or macrophage or myofibroblast infiltration in nude mouse explants. CONCLUSION: The hypothesized biological properties of COX-2 inhibition did not influence lesion number or size in the nude mouse model of endometriosis.