Intraperitoneal Implantation Research Articles

Novel biocompatible intraperitoneal drug delivery system increases tolerability and therapeutic efficacy of paclitaxel in a human ovarian cancer xenograft model

We compared the safety, toxicity, biocompatibility and anti-tumour efficacy of a novel chitosan-egg phosphatidylcholine (ePC) implantable drug delivery system that provides controlled and sustained release of paclitaxel (PTX(ePC)) versus commercial paclitaxel formulated in Cremophor EL (PTX(CrEL)). Toxicity studies were conducted in healthy CD-1 female mice, whereas efficacy studies were performed in the SKOV-3 xenograft model of ovarian cancer. Treatments consisted of intraperitoneal (IP) implantation of drug-free or PTX(ePC) formulations, IP bolus PTX(CrEL), or Cremophor EL (CrEL) vehicle. Toxicity was assessed as number of deaths, weight loss, serum hepatic enzyme levels and histopathological changes. Mice implanted with drug-free or PTX(ePC) formulations did not exhibit observable toxicities, local inflammation or fibrous encapsulation of the implant. In contrast, mice receiving PTX(CrEL) or CrEL encountered significant toxicity, lethality, abnormal peritoneal organ morphology and hepatic inflammation. The maximum tolerable dose (MTD) of PTX(CrEL) was 20 mg/kg/week, whereas PTX doses of up to 280 mg/kg/week were well tolerated when administered as PTX(ePC). Enhanced anti-tumour efficacy was achieved with PTX(ePC) in contrast to PTX(CrEL) with the same total dose of 60 mg/kg PTX. The novel PTX(ePC) formulation is a safer and better tolerated method for PTX administration, with significant increase in MTD and enhanced anti-tumour efficacy, suggesting improved therapeutic index with possible clinical implications in the treatment of ovarian tumours.

Laparoscopic mesh repair of incisional hernia: an alternative to the conventional open repair?

Tension-free incisional hernia repair using alloplastic material increasingly replaces conventional repair techniques. This change resulted in a decreased recurrence rate (50% vs. 10%, respectively). Recently, laparoscopic approaches for the intraperitoneal tension-free mesh application have been introduced. The decreased trauma at the incision site and the reduction in wound infections appear to be the main advantages. The aim of the present study was to evaluate the early and long-term complications as well as patients' contentment. Laparoscopic hernia repair with intraperitoneal polytetrafluroethylene (PTFE) mesh implantation was performed on 62 patients at the Klinikum Grosshadern between 2000 and 2005 (29 males, 33 females age 60.7). Intra- and postoperative complications were registered prospectively and retrospectively analyzed. In addition, 57 patients were evaluated for recurrence, postoperative pain and patient contentment (median follow-up 409 days). A low complication rate was observed in our patient collective. One trocar bleeding occurred. Three patients presented with wound hematoma. The recurrence rate was 8% (2/25). Sixty-two percent of the patients were free of complaints postoperatively. Eighty-five percent would once again choose the laparoscopic approach for incisional hernia repair. The laparoscopic technique was associated with a low recurrence rate, a small rate of wound infections and high patient comfort. Thus, the laparoscopic approach for mesh implantation appears to be a safe and effective method for the treatment of incisional hernias. The efficiency for laparoscopic intraperitoneal mesh implantation, however, should be further evaluated within a prospectively randomized multicenter trial.

In vivo cellularization of a cross-linked matrix by intraperitoneal implantation: a new tool in heart valve tissue engineering

To use in vivo instead of in vitro cell seeding in heart valve tissue engineering. Intraperitoneally preseeded, photo-oxidized bovine pericardial pulmonary valve constructs (group 1) were compared with non-preseeded constructs (group 2) implanted in sheep. All valves functioned normally and were macroscopically intact at explantation [1 week (n = 6) and 1 month (n = 6) in each group], except for one thrombosed leaflet in a group-2 valve at 1 month. Almost 10-fold higher neomatrix deposition and doubling of the leaflet thickness were found in group 1 vs. 2 (P < 0.05). A concomitant significant decrease in leaflet length (15%) was found at 1 month in group 1. The total cross-sectional surface and total amount of collagen of the original matrix remained unchanged in both groups at all times. Immunohistochemistry showed a low immune response, stem/progenitor cell infiltration, appropriated differentiation, and spontaneous endothelialization of the valves. Significantly, increased re-cellularization was found after IP preseeding compared with spontaneous seeding: cell coverage of the leaflet was 71-100 vs. 8-26% (P < 0.05), respectively. Complete re-cellularization can be obtained by IP preseeding of an acellularized cross-linked matrix. Well-functioning valve constructs show cellularization and differentiation into myofibroblast phenotype and concomitant neomatrix deposition.

ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis

BackgroundICI 182,780 (ICI) belongs to a new class of antiestrogens developed to be pure estrogen antagonists and, in addition to its therapeutic use, it has been used to knock-out estrogen and estrogen receptor (ER) actions in several mammalian species. In the present study, the effects and mechanism of action of ICI were investigated in the teleost fish, sea bream (Sparus auratus).MethodsThree independent in vivo experiments were performed in which mature male tilapia (Oreochromis mossambicus) or sea bream received intra-peritoneal implants containing estradiol-17 beta (E2), ICI or a combination of both compounds. The effects of E2 and ICI on plasma calcium levels were measured and hepatic and testicular gene expression of the three ER subtypes, ER alpha, ER beta a and ER beta b, and the estrogen-responsive genes, vitellogenin II and choriogenin L, were analyzed by semi-quantitative RT-PCR in sea bream.ResultsE2 treatment caused an increase in calcium levels in tilapia, while ICI alone had no noticeable effect, as expected. However, pretreatment with ICI synergistically potentiated the effect of E2 on plasma calcium in both species. ICI mimicked some E2 actions in gene expression in sea bream liver upregulating ER alpha, vitellogenin II and choriogenin L, although, unlike E2, it did not downregulate ER beta a and ER beta b. In contrast, no effects of E2 or ICI alone were detected in the expression of ERs in testis, while vitellogenin II and choriogenin L were upregulated by E2 but not ICI. Finally, pretreatment with ICI had a synergistic effect on the hepatic E2 down-regulation of ER beta b, but apparently blocked the ER alpha up-regulation by E2.ConclusionThese results demonstrate that ICI has agonistic effects on several typical estrogenic responses in fish, but its actions are tissue-specific. The mechanisms for the ICI agonistic activity are still unknown; although the ICI induced up-regulation of ER alpha mRNA could be one of the factors contributing to the cellular response.

Microencapsulation of Engineered Cells to Deliver Sustained High Circulating Levels of Interleukin-6 to Study Hepatocellular Carcinoma Progression

Interlukin-6 (IL-6) is a pleitropic cytokine that plays a central role in normal and abnormal hepatic function and response. The aims of the current study were to determine the viability of using cell encapsulation technology to introduce a genetically modified xenogeneic (CHO) cell population to elevate circulating levels of rhIL-6 in a rat model and determine the effects of sustained high rhIL-6 levels on hepatocellular carcinoma (HCC) progression in vivo. An alginate matrix was combined with transfected CHO cells, selected for their ability to synthesize rhIL-6, and used to generate uniform alginate-cell beads. Once encapsulated transfected cells continued to undergo replication, formed colonies within the bead, and synthesized/released large quantities of rhIL-6 into culture medium in vitro. Intraperitoneal implantation of beads into rats resulted in significantly increased circulating and intrahepatic levels of rhIL-6 up to 4 days postimplantation. Prolonged implantation led to the escape of CHO cells from the bead, resulting in a host response and CHO cell death within the bead. Subsequently CHO-IL-6 encapsulated cells were implanted into rats previously inoculated intrahepatically with the H4IIE HCC cell line. These studies demonstrated the maintenance of high circulating/intrahepatic rhIL-6 levels in this model. Despite significantly increased rhIL-6, this technique did not significantly alter the rate of net tumor progression. However, Stat3 activity was significantly increased in both normal liver and HCC tissue resected from animals implanted with CHO-IL-6 cells. Collectively these data demonstrate the short-term viability of using cell encapsulation technology to generate high levels of active circulating and intrahepatic cytokines and raise the possibility of modifying specific signal transduction cascades identified to be important during tumor progression.

The effect of elevated blood cortisol levels on the extinction of a conditioned stress response in rainbow trout

Following previously published observations that a conditioned response (CR) was lost more quickly by rainbow trout ( Oncorhynchus mykiss) exhibiting a high responsiveness to stressors than by low responding individuals this study was designed to investigate the effects of exogenous cortisol on the retention of a CR in unselected rainbow trout. Fish held in isolation were conditioned over a 10-day period by pairing an innocuous signal (conditioned stimulus, CS: a water jet played on the surface of the tank water) with a mild stressor (unconditioned stimulus, US: 30 min of confinement). This resulted in a brief elevation of plasma cortisol levels (the CR) when the fish was exposed to the CS only. The effect of exogenous cortisol on the retention of the CR was evaluated by comparing the performance of fish that received cortisol-containing slow-release intraperitoneal implants, with fish receiving vehicle-only implants. Retention of the CR was assessed at intervals up to 35 days after conditioning ceased. The CR was considered to be evident when 30 min following presentation of the CS, mean plasma cortisol levels were significantly higher in conditioned than untrained fish. On day 1 both cortisol-implanted and vehicle-implanted conditioned fish exhibited a CR. However, from day 5 onwards the CR was observed only in the vehicle-implanted and conditioned group. This finding indicates that administration of cortisol accelerated the extinction of the CR in the cortisol-implanted fish, suggesting that elevated plasma cortisol levels can impair memory processes in rainbow trout.

Prespawning stress in farmed Atlantic salmonSalmo salar: maternal cortisol exposure and hyperthermia during embryonic development affect offspring survival, growth and incidence of malformations

In the current study, mature female Atlantic salmonSalmo salarwere given intraperitoneal cortisol implants with the purpose of elucidating potentially detrimental effects on offspring survival, growth, morphological development and also the ability of prenatally stressed offspring to cope with an environmental stressor, typified by a period of mild hyperthermia. Augmented levels of maternal cortisol inflicted a range of progeny somatic parameters, as reflected in increased mortality, reduced fork length and mass, diminished yolk‐sac volume, decelerated yolk‐sac utilization and, to some extent, enhanced prevalence of morphological malformations. The most pronounced consequences on offspring performance were demonstrated in specimens exposed to both enhanced prenatal cortisol and a subsequent episode of hyperthermia. This accentuates the importance of knowledge on how the maternal endocrinological state during gametogenesis may impinge on offspring characters in farmed Atlantic salmon, and further substantiates the necessity of incorporating maternal effects when evaluating rearing conditions and animal welfare in commercial aquaculture.

Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice

Androgens promote anabolism in skeletal muscle; however, effects on subsequent muscle function are less well defined because of a lack of reliable experimental models. We established a rigorous model of androgen withdrawal and administration in male mice and assessed androgen regulation of muscle mass, structure, and function. Adult C57Bl/6J male mice were orchidectomized (Orx) or sham-operated (Sham) and received 10 wk of continuous testosterone (T) or control treatment (C) via intraperitoneal implants. Mass, fiber cross-sectional area (CSA), and in vitro contractile function were assessed for fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles. After 10 wk, Orx+C mice had reduced body weight gain (P < 0.05), seminal vesicle mass (P < 0.01), and levator ani muscle mass (P < 0.001) compared with Sham+C mice, and these effects were prevented with testosterone treatment. Orx+T mice had greater EDL (P < 0.01) and SOL (P < 0.01) muscle mass compared with Orx+C mice; however, median fiber CSA was not significantly altered in these muscles. EDL and SOL muscle force was greater in Sham+T compared with Orx+C mice (P < 0.05) in proportion to muscle mass. Unexpectedly, Orx+T mice had increased fatigue resistance of SOL muscle compared with Orx+C mice (P < 0.001). We used a rigorous model of androgen withdrawal and administration in male mice to demonstrate an essential role of androgens in the maintenance of muscle mass and force. In addition, we showed that testosterone treatment increases resistance to fatigue of slow- but not fast-twitch muscle.

Sex steroid regulation of brain glutamic acid decarboxylase (GAD) mRNA is season-dependent and sexually dimorphic in the goldfish Carassius auratus

GABA, the major inhibitory neurotransmitter of the vertebrate brain, has been shown to play an important role in vertebrate reproduction by regulating LH release and sexual behavior. We have studied the expression of the GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), in goldfish throughout the reproductive cycle in May (mature), November (early gonadal recrudescence) and February (late gonadal recrudescence) and in response to implanted sex steroids. Levels of GAD 67 and GAD 65 mRNA levels in the hypothalamus of both males and females were highest in the early stages of gonadal recrudescence. In the telencephalon, a different seasonal pattern of GAD expression was evident. The telencephalic expression GAD 67, GAD 65 and a novel isoform, GAD3, were highest in sexually mature fish in May. Five-day intraperitoneal implantation of gonad-intact fish with testosterone (T), estradiol (E2) or progesterone (P4) did not affect GAD expression in November and February. This is in contrast to results in May when sex differences in steroid responsiveness were evident. Progesterone decreased hypothalamic GAD 67 and GAD 65 in females and was without effect in males. All other treatments did not alter GAD 67, GAD 65 or GAD3 expression in the hypothalamus. Both T and P4 decreased GAD 67 and GAD 65 levels in the telencephalon of male goldfish but had no effect in females. Serum sex steroid levels in control and implanted mature males and females in May were similar so it is unlikely that sex differences in the GAD responses were a result of differences in serum sex steroid levels. These contrasting effects of sex steroids on males and females suggest important sex differences in the regulation of the GADs in sexually mature goldfish.

Evaluation of implant/host tissue interactions following intraperitoneal implantation of porcine dermal collagen prosthesis in the rat

An ideal prosthesis for ventral hernia repair should minimize development of postoperative adhesions. This study evaluates adhesion formation following intraperitoneal implantation of acellular porcine dermal collagen (PDC) and polypropylene (PP) mesh in 16 rats. Implant placement alternated left/right. Sacrifice (4 or 12 weeks) was randomized. Methods included adhesion grading (extent, severity, required dissection method) and histological evaluation. At 4 weeks, 7 of 8 PDC specimens and 0 of 8 PP implants were adhesion-free; results were identical at 12 weeks. Four-week adhesions were less developed than 12-week adhesions. Histology showed mononuclear cell foreign body reaction and disorganized collagen deposition for PPs compared to infiltration with neovascular channels and qualitatively less intense foreign body reaction for PDCs. PDC exhibits fewer adhesions and more favorable cellular response than PP in the rat.

Multiple myeloma in a murine syngeneic model:modulation of growth and angiogenesis by a monoclonal antibody to kininogen.

Multiple myeloma (MM), a B-cell malignancy characterized by proliferation of monoclonal plasma cells remains incurable. Murine plasma cell tumors share common features with human MM. We used two cell lines (B38 and C11C1) derived from P3X63Ag8 myeloma cells. The new cell lines were implanted subcutaneously in the strain of origin (Balb/c mice) and used as a model to monitor the effects of C11C1 monoclonal antibody (mAb) to kininogen (HK). We assessed their behavior by intraperitoneal and subcutaneous implantation, by implanting them together and by treating B38-MM with purified mAb C11C1. We evaluated growth, microvascular density (MVD), and cellular expression of urokinase-type plasminogen activator-receptor (uPAR), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), bradykinin-1 receptor (B1R), bradykinin-2 receptor (B2R) and HK. We found that both MM-cell-lines are uPAR positive, that mAb C11C1 inhibits its own tumor growth in vivo, slows down B38-MM growth rate when both MM are implanted together and when mAb C11C1 is injected intraperitoneally. MAb C11C1-treated-MM showed decreased MVD and HK binding in vivo without FGF-2, B1R or B2R expression changes. We propose that the B38-extramedullary-myeloma-model is a useful tool to study the interactions of this hematopoietic tumor and its environment and that mAb C11C1 may improve the efficacy of conventional MM treatment with minimal side effects.

Development of a surgical approach for telemetering guinea pigs as a model for screening QT interval effects

Introduction Identifying a compound's risk of potentially producing Torsade de Pointes (TdP)/QT interval prolongation has become a goal early within the drug development process. Our aim was to develop a surgical approach for instrumenting guinea pigs for collecting ECG data. Methods Male Dunkin Hartley guinea pigs (386–661 g) were surgically implanted with telemetry transducers for the measurement of lead II ECG and arterial blood pressure. Using strict aseptic techniques and isofluorane anaesthesia (0.5–5.0%), one of the three implantation procedures was used. In Phase I the animals were either implanted intraperitoneally (abdominal aorta cannulated) or subcutaneously (carotid artery cannulated). In Phase II all animals were implanted subcutaneously and the subcutaneous pocket formed either with a single incision, as in Phase I, or a double incision. Results Phase I—During intraperitoneal implantation, rupture of the aorta occurred in 50% of the animals. The remaining animals were terminated between 2 and 14 days postsurgery on human grounds. All of the animals implanted subcutaneously survived the surgical procedure and the following 28 days. Skin thinning over the implant occurred in 25% of the animals in weeks 5–6. Phase II—Following single incision subcutaneous implantation 72% of the animals were terminated within the 28-day postsurgery due to skin rupture over the implant body, with only 22% of the animals viable after 28 days. Following double incision subcutaneous implantation 86% of animals were viable after 28 days and thus the recommended method for implantation. Discussion The improvements to the surgical approach have improved survival rates and increased the potential for robust, long term use of telemetered guinea pig colonies for screening for QT prolonging potential and additional cardiovascular assessment in vivo.

In vitro and in vivo characterization of a novel biocompatible polymer–lipid implant system for the sustained delivery of paclitaxel

Recently, a novel chitosan-based implantable formulation (chitosan-ePC) was developed to provide controlled, local release of paclitaxel (PTX) for the treatment of ovarian tumors. Hence, the objective of this study was to evaluate this delivery system in vitro in human ovarian SKOV-3 cells and in vivo in mice with intraperitoneal implants of drug-free or 14C-PTX–chitosan-ePC films. In vitro, 14C-PTX–chitosan-ePC implants (10 mg) provided zero-order constant release of 0.92 ± 0.03 pg/day PTX over 5 days. Released PTX retained dose-dependent activity; effectively inhibiting SKOV-3 proliferation with an ED 50 of 211 ng/ml of released PTX. Drug-free implants did not affect cell viability or cell morphology of SKOV-3 cells. A sustained, zero-order release of PTX was also seen in vivo over a 2 week period in mice implanted with 14C-PTX–chitosan-ePC films. Correlations between the in vitro and in vivo release of PTX was highly significant ( R 2 = 0.975). After 2–4 weeks, mice with chitosan-ePC implants did not demonstrate any signs of encapsulation, inflammation or infection. Overall, our in vitro and in vivo results demonstrated zero-order drug release and biocompatibility of the novel chitosan-ePC film. This indicates potential usefulness of chitosan-ePC implants in the sustained and local delivery of anti-neoplastic agents.

Electrocorticographic and deep intracerebral EEG recording in mice using a telemetry system

Telemetric EEG recording plays a crucial role in the neurological characterization of various transgenic mouse models giving valuable information about epilepsies and sleep disorders in humans. In the past different experimental approaches have been described using tethered systems and jacket systems containing recorders. A main disadvantage of these is their sometimes unphysiological, restraining character. Telemetric EEG recording overcomes most of these disadvantages and allows precise and highly sensitive measurement under various physiological and pathophysiological conditions and different stages of consciousness, as during seizure activity and different sleep stages. Here we present the first contiguous, detailed description of a successful and quick technique for intraperitoneal implantation or subcutaneous pouch implantation of a radiofrequency transmitter in mice and subsequent lead placement in both epidural and deep intracerebral position. Preoperative preparation of the mice, suitable anesthesia, as well as postoperative treatment including pain management are described in detail to provide optimal postoperative recovery. Finally, we display examples of electrocorticograms and deep intracerebral recordings, present strategies to maximize signal-to-noise ratio, paying special attention to major pitfalls and possible artefacts occurring in telemetric EEG recording in mice.

Laparoskopischer Bruchlückenverschluss von Narbenhernien - Eine Alternative zu konventionellen Verfahren?

Tension-free incisional hernia repair using alloplastic material increasingly replaces conventional repair techniques. The aim of the present study was to evaluate the early and long-term complications as well as patients' satisfaction. Laparoscopic hernia repair with intraperitoneal mesh implantation (PTFE) was performed on 28 patients at the Klinikum Grosshadern between 2000 and 2003 (16 males, 12 females, average age 61.2). Intra- and postoperative complications were registered retrospectively. In addition, 25 patients were evaluated for recurrence, postoperative pain and patient contentment (median follow-up 383 days). A low complication rate was observed in our patient collective. One trocar bleeding occurred. 2 patients presented with wound hematoma. The recurrence rate was 8 % (2/25). 60 % of the patients were free of pain postoperatively. 88 % would once again choose the laparoscopic approach for incisional hernia repair. The laparoscopic technique was associated with a low recurrence rate, a small rate of wound infections and high patient comfort. Thus, the laparoscopic approach for mesh implantation appears to be a safe and effective method for the treatment of incisional hernias. The efficiency of laparoscopic intraperitoneal mesh implantation, however, should be evaluated within a prospectively randomized multicenter trial.

Reduction of GAG storage in MPS II mouse model following implantation of encapsulated recombinant myoblasts

Hunter syndrome, mucopolysaccharidosis type II (MPS II), is a X-linked inherited disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS), involved in the lysosomal catabolism of the glycosaminoglycans (GAG) dermatan and heparan sulfate. Such a deficiency leads to the intracellular accumulation of undegraded GAG and eventually to a progressive severe clinical pattern. Many attempts have been made in the last two to three decades to identify possible therapeutic strategies for the disorder, including gene therapy and somatic cell therapy. In this study we evaluated the intraperitoneal implantation of allogeneic myoblasts over-expressing IDS, enclosed in alginate microcapsules, in the MPS II mouse model. Animals were monitored for 8 weeks post-implantation, during which plasma and tissue IDS levels, as well as tissue and urinary GAG contents, were measured. Induced enzyme activity occurred both in the plasma and in the different tissues analyzed. A significant decrease in urinary undegraded GAG between the fourth and the sixth week of treatment was observed. Moreover, a biochemical reduction of GAG deposits was measured 8 weeks after treatment in the liver and kidney, on average 30 and 38%, respectively, while in the spleen GAG levels were almost normalized. Finally, the therapeutic effect was confirmed by histolochemical examination of the same tissues. Such effects were obtained following implantation of about 1.5 x 10(6) recombinant cells/animal. Taken together, these results represent a clear evidence of the therapeutic efficacy of this strategy in the MPS II mouse model, and encourage further evaluation of this approach for potential treatment of human beings.

Adrenal Metastasis from Ovarian Carcinoma

1711 57-year-old woman with serous adenocarcinoma confined to the ovary was treated with transabdominal hysterectomy, bilateral salpingooophorectomy, and adjuvant chemotherapy. Two years later she developed recurrent disease involving the retroperitoneal lymph nodes. She was treated with second-line chemotherapy that resulted in complete remission. Surveillance CT performed 1 year later showed a new 1.0-cm nodule in the left adrenal gland (Fig. 1A). No further imaging or intervention was performed at that time. A CT scan obtained 1 year later showed that the adrenal nodule had increased in size to 2.0 cm and a 1.2-cm nodule had developed in the pancreatic tail (Fig. 1B). The remainder of the abdominal and pelvic CT was unremarkable, with no evidence of metastatic disease elsewhere. Because no other primary tumor was known and the left adrenal lesion was enlarging, a CT-guided core biopsy of the adrenal lesion was performed using an 18-gauge needle. Pathologic examination revealed the presence of high-grade serous adenocarcinoma of ovarian origin (Fig. 1C). The diagnosis was supported by immunochemical stains positive for cancer antigen 125 and cytokeratin 7 (CK-7). The patient declined further treatment. Follow-up CT performed 4 months after the biopsy showed further growth of the left adrenal and pancreatic lesions. Ovarian carcinoma can spread by peritoneal implantation, lymphatic invasion, and hematogenous dissemination. Intraperitoneal implantation is the primary mode of spread of ovarian cancer, although hematogenous metastases are considered uncommon. However, autopsy and cross-sectional imaging studies have proved that the prevalence of metastases in advanced disease is higher than previously recognized [1]. This may be related to improvements in therapy with the result that patients who have advanced disease are living longer and are more frequently imaged. The reported prevalence of adrenal and pancreatic metastases in patients with ovarian cancer at autopsy is 15% and 21%, respectively [1]. However, radiologic descriptions of adrenal metastases from an ovarian primary tumor are rare. To our knowledge, only one report of the imaging appearance of adrenal metastases from an ovarian primary tumor has been published in the Englishlanguage literature [2]. That case describes large bilateral adrenal metastases from smallcell neuroendocrine carcinoma that were removed surgically. Pancreatic metastases from ovarian carcinoma are uncommon [3, 4], and large lesions involving the pancreas also have been reported. To our knowledge, we report the first case of simultaneous adrenal and pancreatic metastases in a patient with serous carcinoma of the ovary. The adrenal glands and pancreas are uncommon sites of metastatic disease from ovarian cancer, especially in the absence of disease elsewhere. Clinicians and radioloAdrenal Metastasis from Ovarian Carcinoma

Training, Experience, and Opinions of Researchers Who Use Surgical Techniques to Implant Telemetry Devices into Fish

Intraperitoneal implantation of telemetry devices in fishes has become commonplace in fisheries science, yet little is known about the training and experience of practicing fish surgeons. We used a survey to characterize the training, experience, and opinions of researchers who use surgical techniques to implant telemetry devices in fishes. The experience level of the 177 respondents varied from 0 to 25 years of experience and 5 to 5,000 fish surgeries, and it was apparent that there was no consistent method of training in surgical techniques, with many of the respondents indicating they learned from trial and error. Very few of the respondents had been formally tested to assess their level of surgical competency, although the majority recognized that surgical experience was important and believed that a minimum level of experience should be required prior to engaging in fish surgery. Respondents identified a need for more effective training materials and perhaps some levels of international standards. The consensus of respondents was that the most effective surgical training would include coupling theoretical instruction/workshops with hands-on mentoring. We suggest that workshop materials (i.e., curricula and manuals) should be developed by a diverse group of surgeons with experience operating on fish. These materials must be peer reviewed, the courses should be accessible and affordable to all fisheries students and professionals, and the results need to be evaluated to determine if the program is achieving learner outcomes. Furthermore, a formal venue for individuals who conduct surgery on fish is needed to exchange ideas, and to link novices with appropriate mentors. Information derived from this study will provide a starting point for understanding issues associated with fish telemetry surgery and enable development of effective training materials for future and practicing fish surgeons.

Inflammatory antigens of Brugia malayi and their effect on rodent host Mastomys coucha

The study was aimed at identifying pro- and anti-inflammatory cytokine releasing potential of Brugia malayi adult worm fractions and their role in filarial infection and pathogenesis. THP-1 cells were incubated with soluble somatic Brugia malayi adult worm extract (BmAS) and its Sephadex G-200 fractions BmAFI, BmAFII and BmAFIII and the effect of the fractions on parasitological, immunological and lymph node parameters was assessed in Mastomys coucha. BmAFII stimulated the pro-inflammatory TNF-alpha, IL-1beta and IL-6 release; IL-10 release was insignificant. Sensitization of animals with BmAFII and subsequent intraperitoneal implantation of worms enhanced CMI response. BmAFII also increased lymph node weight and cellularity, stimulated lymph node mast cells and eliminated intraperitoneally instilled worms. BmAFI stimulated several folds more release of IL-10, whereas TNF-alpha release was negligible. Sensitization with BmAFI elicited low CMI responses, moderately stimulated mast cells and facilitated survival of implanted adult parasites. Fifty percent of naive animals exposed to BmAFI showed oedematous lymph nodes and increased node weight. NCP-bound molecules corresponding to BmAFI and II showed cytokine-stimulating potential in vitro. It is concluded that BmAFII is protective and stimulates pro-inflammatory cytokines, whereas BmAFI facilitates parasite survival and stimulates IL-10.

Circadian renal rhythms influenced by implanted encapsulated hANP-producing cells in Goldblatt hypertensive rats.

Renal excretion in experimental hypertensive rats implanted with encapsulated human atrial natriuretic peptide (hANP)-producing cells is circadian periodic. Chinese hamster ovary (CHO) cells transfected with the plasmid hANP-cDNA were encapsulated in biocompatible polycaprolactone capsules for intraperitoneal implantation into two-kidney, one-clip (2K1C) hypertensive rats. During a 12:12 light-dark cycle, as compared to control CHO cells, the implantation of encapsulated hANP-producing CHO cells was associated with an increase in the net excretion of water, sodium and potassium, and with a reversal of the advanced circadian phases related to renovascular hypertension in 2K1C rats. The increase in blood pressure postimplantation was delayed, and increases in renal blood flow, glomerular filtration rate, sodium output, urinary excretion and urinary cyclic GMP concentrations were also found. Implantation of encapsulated hANP-producing cells affects circadian rhythms in kidney excretion functions of 2K1C rats, and may be useful for the treatment of cardiovascular disease.