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Absorption of 17 beta-estradiol in a neovagina constructed from the peritoneum.

Estrogen absorption from the neovagina was studied by administering 2.0 mg of micronized 17 beta-estradiol (E2) neovaginally to 6 patients. The neovagina in each patient was constructed by using the peritoneum from the pouch of Douglas. A mean peak of circulating E2 concentrations more than 15-times the basal level was achieved 90 min after the application. Until 12.5 h after the application, the E2 levels were significantly (P less than 10(-6)) elevated. FSH levels were significantly (P = 0.003) changed in comparison to the basal serum concentration. There was no significant (P = 0.08) change in LH levels. The resorption of estradiol from the neovagina is similar to that seen in women with normal vaginas.

Administration, Topical↗

Mechanism of complement-induced stimulation of prostacyclin production by isolated rabbit peritoneum.

The interaction between the complement system and prostaglandin synthesis has not thoroughly been explored, although both mediators are known to be involved in inflammatory reactions and endotoxic shock. When rabbit peritoneum, a rich source of prostacyclin forming activity was incubated in serum in which the complement system was activated (CVF, LPS, zymosan), the tissue produced significantly more PGI2, when compared with appropriate controls, indicating that by activation of the complement, factors were generated that stimulated PGI2 biosynthesis. Further results indicated that tryptic cleavage products of complement factor C3 and C5 also led to the appearance of PGI2 releasing principles with a molecular weight of about 7000-11000. The stimulation of PGI2 biosynthesis was explained by enhanced release of AA, and not due to increased activity of cyclo-oxygenase or PGI2 synthetase. Our results suggest that complement-derived products may promote the supply of prostaglandins at the site of inflammation.

6-Ketoprostaglandin F1 alpha↗

Resection of diaphragmatic peritoneum and muscle: role in cytoreductive surgery for ovarian cancer.

Fourteen patients undergoing primary cytoreductive surgery for stage III ovarian malignancies had diaphragmatic peritoneum, muscle, or both resected in an attempt to remove all metastatic disease greater than 0.5 cm in diameter. Resection was completed in 13 of 14 patients (93%), all obtaining optimal cytoreduction. Size of resected specimens varied from 12 x 7 to 17 x 11 cm. The mediastinum was entered in two patients. Four patients had resection of diaphragmatic muscle. All defects were closed primarily and a thoracostomy tube was placed. One patient who did not have muscle resection had a 30% pneumothorax that spontaneously resolved. No subdiaphragmatic hematomas or abscesses occurred. Time (mean 65 min, range 40-150 min) and blood loss (mean 175 ml, range 100-1500 ml) for the surgery depended upon extent of disease. One procedure was terminated due to bleeding from a lacerated liver capsule. We conclude that diaphragmatic peritoneum/muscle resection can be completed successfully with acceptable morbidity.

Diaphragm↗

Studies of the permeability of isolated porcine peritoneum to nutrients: saccharides.

Isolated peritoneal membrane, freshly harvested from pigs, was studied in vitro to determine the permeability of the membrane to saccharide nutrients. Studies were performed with glucose and sucrose at various transmembrane gradients ranging from 150 to 600 mosm/liter (mmol/liter) and with polysaccharide at a 300 mosm/liter gradient. Findings indicate that flux of these nutrients across the isolated peritoneum is related to molecular weight and that sufficient kilocalories will traverse the membrane to provide for adequate carbohydrate nutrition (calculated to deliver more than 3000 kcal/day at gradients of 150 mosm/liter). Polysaccharide flux studies suggest that carbohydrate calories may be provided in the form of complex molecules and not only in the form of glucose. Studies of 1:1 serum and polysaccharide mixtures showed the conversion of polysaccharide to glucose by serum in vitro. When rats were given intraperitoneal polysaccharide their blood glucose levels rose promptly although they remained fasting, suggesting an in vivo conversion also occurs. These findings provide support for use of polysaccharides intraperitoneally as means to reduce the osmolarity of fluid administered for nutritional support; this would increase tolerance while still providing ample calories. The in vitro apparatus used in these studies provides a mechanism to study individual nutrients and yields highly reproducible results. These studies add further evidence that intraperitoneal nutrition is feasible.

Animals↗

Efficacy of autologous peritoneum as a biological membrane in cardiac surgery.

The risks for reoperative cardiac surgery are related to the presence of intrapericardial adhesions and the possibility of catastrophic injury at repeat sternotomy. In an attempt to develop an improved pericardial substitute and vascular patch, the feasibility of using autologous peritoneum was evaluated. Twelve mongrel dogs were studied. A peritoneal-rectus fascia patch, including the overlying posterior rectus sheath was harvested, via a lateral abdominal incision, and stored in normal saline. In the first group of six animals, a pulmonary artery (PA) window was created and then closed with the peritoneal-rectus fascia patch. In the second group a secundum atrial septal defect was created and then closed with the peritoneal patch on cardiopulmonary bypass (CPB). In each animal, the peritoneal-rectus fascia patch was used to permit pericardial closure. Autopsies performed at 90 days postoperatively revealed only slight intrapericardial adhesion formation and a mild epicardial reaction. Histological examination of the peritoneal-rectus fascia patches revealed intact morphology with active fibroblasts and smooth muscle cells. Proline 14C absorption and autoradiography detected viable cells in the implanted patches. These findings suggest that a peritoneal-rectus fascia allograft could be useful as a biological membrane, and as a satisfactory pericardial substitute in the development of strategies to reduce the risk for reoperative cardiac surgery.

Animals↗

Reconstruction of the vena cava with the peritoneum: the effect of temporary distal arteriovenous fistula on patency (an experimental study).

OBJECTIVE: To determine the effect of increasing inferior vena cava blood flow by means of distal arteriovenous fistula on the patency of a peritoneal tube graft. MATERIALS AND METHODS: In 16 mongrel dogs, a 3-4 cm long circular defect was created at the infrarenal inferior vena cava. The defect was interposed with peritoneal tube graft. A temporary distal femoro-femoral arteriovenous fistula was also constructed in 8 dogs just after the caval interposition. Graft patency was evaluated by Doppler ultrasonography and angiography. Histological evaluation was also performed. RESULTS: Seven dogs in each group survived. All control grafts occluded within the first week, compared to no occlusions in fistula group (Fisher's exact test, p<0.005). However one 'fistula' dog with a still patent graft was sacrificed on the 18th day due to ultrasonographically occluded arteriovenous fistula. CONCLUSION: In dogs, the peritoneum may be used as graft material for reconstruction of the inferior vena cava, provided a distal arteriovenous fistula is constructed.

Animals↗

Identification of macrophages at the site of peritoneal injury: evidence supporting a direct role for peritoneal macrophages in healing injured peritoneum.

OBJECTIVE: To determine if peritoneal macrophages are present at the site of a surgical injury to the peritoneum during wound healing. DESIGN: Controlled research study. SETTING: Academic research laboratory. EXPERIMENTAL MODEL: A murine model of peritoneal wound healing. INTERVENTION(S): Intraperitoneal injection of polystyrene beads 1 hour after a surgical peritoneal injury to identify peritoneal macrophages. MAIN OUTCOME MEASURE(S): Presence of peritoneal macrophages at the site of the healing wound as determined by intracellular polystyrene beads on transmission electron microscopy 1, 3, 7, and 14 days after injury. RESULT(S): Peritoneal macrophages were easily distinguished from other cell types by the phagocytosis of polystyrene beads. One day after injury, peritoneal macrophages were adherent to the wound surface. By 3 days, mesothelial cells began covering the peritoneal macrophages at the wound surface and peritoneal macrophages were identified deep within the wound. Seven days after injury, the mesothelial layer was completely reconstituted, but peritoneal macrophages persisted within the healing would below the surface mesothelium. CONCLUSION(S): These data indicate that peritoneal macrophages are present at the peritoneal injury site throughout the healing interval and are consistent with these macrophages having a critical role in peritoneal wound healing.

Animals↗

Regulation of NK cell function in vivo by the dose of tumour transplanted in the peritoneum.

Antigen dose is known to regulate T cell activation and anergy. Similarly, dose of antigen also regulates NK cell lytic potential and phenotype development. Resident peritoneal cells of rat contain a small population of NK and NKT cells. Inoculation of AK-5 tumour cells intraperitoneally modulate the cytotoxic function of NK and NKT cells present in the peritoneal exudate cells (PEC) in a dose dependent manner. Low dose of tumour causes activation of NK and NKT cell cytotoxic function and enhanced NK and NKT cell population in PEC, whereas, high doses of tumour cause inactivation of NK and NKT cell cytotoxic function and depletion of the two sub-populations in the peritoneum. Different doses of tumour inoculation in the peritoneal cavity did not suppress the cytotoxic function of NK cells from spleen suggesting that a direct interaction between NK cells and tumour cells is required for the suppression of NK cell cytotoxic function. Tumour inoculation induced secretion of IL-2, IL-12, IFN-gamma and TNF-alpha by tumour infiltrating mononuclear cells (TIM) in ascitic fluid as well as in serum. The levels of IL-2, IL-12, IFN-gamma and TNF-alpha secretion were higher in animals, which rejected tumours as compared with the animals that failed to reject the tumours. Injection of anti IL-12 and anti IFN-gamma antibody reduced the survival rate of tumour injected animals, however, anti IL-2 antibody had no effect on the survival of animals. Following incubation with AK-5 tumour cells, activated NK cells upregulated perform expression, whereas, there was upregulation of CD95 expression in inactivated NK cells.

Animals↗

Functional longevity of the human peritoneum: how long is continuous peritoneal dialysis possible? Results of a prospective medium long-term study.

Long-term peritoneal dialysis requires the maintenance of the transport function of the peritoneal membrane, and appropriate studies of possible changes are necessary. The quantification of peritoneal mass transfer coefficients (MTCs) has been judged to be the ideal method for the evaluation of peritoneal diffusion. The aim of the present study was to show the results of the prospective evaluations in long-term continuous ambulatory peritoneal dialysis patients. We have studied the clinical incidents and peritoneal function of 56 patients who started continuous ambulatory peritoneal dialysis between 1980 and 1988, and have completed at least 3 years of follow-up. Ultrafiltration capacity was calculated with a standardized formula. All patients were studied for peritoneal diffusion of urea and creatinine at least once a year. The evaluation consisted of a kinetic study done by means of a peritoneal equilibration curve for urea and creatinine, applying a bicompartmental mathematical model to calculate the MTCs. The sequential mean values for urea-MTC did not show significant changes over the observation period (20.7 +/- 5.9 mL/min for the first year v 19.8 +/- 6 mL/min for the fifth year). Creatinine-MTC values showed a significant increase over this period in the paired data analysis. The decrease of the urea-MTC to creatinine-MTC ratio may be an early and appropriate index for measuring these changes when the individual values are in the normal range. On the other hand, peritoneal ultrafiltration capacity significantly decreased over this period (1,800 +/- 530 mL/d v 1,400 +/- 600 mL/d, P < 0.01). The high rate of accumulated days of peritoneal inflammation was related to these significant changes, and thus may be proposed to be a good prognostic index of long-term peritoneal survival. These long-term functional changes might be related to the effect of injuries on the preservation of the normal peritoneal structure. We conclude that after 5 to 11 years, the human peritoneum shows functional stability (diffusion and water transport) in patients with low rates of peritoneal inflammation. With a few exceptions, represented by patients with a high rate of peritoneal inflammation, long-term peritoneal dialysis accomplished its newly entrusted task.

Adolescent↗

Chemical sympathectomy increases numbers of inflammatory cells in the peritoneum early in murine listeriosis.

Here, we investigated the effects of sympathectomy on systemic bacterial loads following infection with Listeria monocytogenes, and on innate and specific immune responses in the peritoneum. Sympathectomy decreased systemic bacterial loads, and increased the number of peritoneal leukocytes and the percentage of peritoneal macrophages three days postinfection. This suggests that sympathectomy-induced decreases systemic bacterial loads are associated with increased recruitment of inflammatory cells into tissues during the innate immune response.

Animals↗

Composition of the extracellular matrix of the peritoneum.

OBJECTIVE: To localize the extracellular matrix proteins collagen I, collagen IV, fibronectin, and laminin in the peritoneal membrane. STUDY DESIGN: Peritoneal biopsies (n = 13) from the anterior abdominal wall and the uterine serosa (n = 3) were incubated with antibodies to collagen IV, laminin, collagen I, and fibronectin. Specimens were examined using light and confocal laser scanning microscopy. RESULTS: All of the extracellular matrix (ECM) proteins were present immediately under the mesothelium. Collagen (Col) IV and laminin (LM) were seen in the smooth muscle of microvascular structures, in the subendothelial basement membrane, and were present in a fascicular pattern in the peritoneal stroma. Collagen I was distributed diffusely in the peritoneal stroma. Fibronectin was also present in the subendothelial basement membrane. CONCLUSIONS: The resolution of the confocal microscope allowed for localization of extracellular matrix proteins in relation to the mesothelium. The presence of collagen IV, laminin, collagen I, and fibronectin under the mesothelium suggests that cells invading the peritoneum must have the ability to degrade and remodel this matrix.

Adult↗

Hydraulically-induced convective solute transport across the rabbit peritoneum.

Transport of solutes during osmotically-induced transperitoneal ultrafiltration is less than would be predicted based upon rates of transperitoneal solute diffusion. Previous workers have hypothesized that osmotically-induced convective solute transport occurs only in small pores at the arteriolar end of peritoneal capillaries, whereas solute diffusion occurs only through large venular pores. We tested this heteroporosity hypothesis in the eviscerated New Zealand White rabbit by determining sieving coefficients (S) for creatinine, p-aminohippurate (PAH) and neutral dextran during hydraulically-induced transperitoneal ultrafiltration (N = 13). A hydraulically-induced driving force directs convective solute transport through the same capillary pores employed for diffusion; therefore S for all solutes should approach unity if the heteroporosity hypothesis is valid. S for creatinine and PAH were respectively 0.72 +/- 0.03 and 0.67 +/- 0.05, values lower than unity and not different from those previously determined during osmotically induced ultrafiltration. Mean S for dextran were relatively independent of molecular size, ranging from 0.50 at 13 A to 0.40 at 50 A. Thus, dextran S were higher than those previously determined during osmotically induced ultrafiltration yet still less than unity. Control experiments (N = 6) suggested that only surface area and not transport characteristics were altered by evisceration. These observations demonstrate that the heteroporosity hypothesis fails to completely describe both diffusive and convective transport properties of the peritoneum.

Animals↗

Role of mesothelial cell-derived granulocyte colony-stimulating factor in interleukin-17-induced neutrophil accumulation in the peritoneum.

Recent studies suggest that peritoneal CD4(+) T lymphocytes may control recruitment of polymorphonuclear leukocytes (PMN) during peritonitis by an interleukin-17 (IL-17)-dependent mechanism. IL-17 and granulocyte colony-stimulating factor (G-CSF) have been proposed to form an axis that regulates PMN transmigration. Here we report on the role of G-CSF released by human peritoneal mesothelial cells (HPMCs) in IL-17A-mediated peritoneal PMN accumulation. In vitro exposure of HPMCs to IL-17A resulted in a time- and dose-dependent release of G-CSF. This effect was related to the induction of G-CSF mRNA and mediated through the nuclear factor-kappaB (NF-kappaB) pathway. The novel observation was that IL-17A-stimulated NF-kappaB activation in HPMCs followed a biphasic profile, with an early induction (45 min), followed by the return to basal levels (90 min), and a delayed induction (3 h). Tumor necrosis factor alpha synergistically amplified IL-17A-induced G-CSF production by enhanced NF-kappaB activation and through stabilization of G-CSF mRNA. Intraperitoneal (i.p.) administration of IL-17A in Balb/c mice resulted in increased local levels of G-CSF and selective PMN accumulation. Administration of anti-G-CSF blocking antibody before IL-17A injection significantly reduced the IL-17A-triggered PMN infiltration. This effect occurred despite increased i.p. levels of PMN-specific chemokines KC and macrophage inflammatory protein-2 seen in animals treated with anti-G-CSF antibody. These data demonstrate that the mesothelium-derived G-CSF plays an important role in IL-17A-induced PMN recruitment into the peritoneum.

Animals↗

Red blood cells inhibit tumour cell adhesion to the peritoneum.

BACKGROUND: Perioperative blood transfusion has been associated with increased tumour recurrence and poor prognosis in colorectal cancer. Blood loss in the peritoneal cavity might be a tumour-promoting factor for local recurrence. The aim of this study was to investigate whether blood in the peritoneal cavity affects local tumour recurrence. METHODS: In an established in vivo rat model the effect of 1.5 ml syngeneic whole blood on tumour cell adhesion and tumour growth was investigated. In the same model the effect of 1.5 ml pure red blood cell (RBC) concentrate and 1.5 ml RBC-derived substances on tumour cell adhesion was studied. In an established in vitro model the effect of increasing numbers of RBCs (0-250 bx 10(6)) on tumour cell adhesion and tumour growth was assessed. RESULTS: Both the presence of blood and RBC concentrate in the peritoneal cavity prevented tumour cell adhesion in vivo (overall P </= 0.001 and P </= 0.05 respectively), rather than promoting adherence. RBC concentrate and RBC-derived substances had a comparable inhibitory effect on tumour cell adhesion. In in vitro studies RBCs inhibited tumour cell adhesion but not tumour growth. CONCLUSION: RBC-derived factors prevent tumour cell adhesion to the peritoneum, and consequently tumour recurrence.

Animals↗

Surface alterations in the bovine pelvic peritoneum following rectal examination of reproductive organs: a scanning electron microscopy study.

The aim of the present study was to evaluate possible injury provoked by an intensive reproductive programme based on rectal palpation in the cow. Alterations to the mesothelial surface of the peritoneum and to the oviductal mucosa were explored by scanning electron microscopy (SEM). Nine multiparous Friesian cows were selected from each of two commercial dairy herds. Cows in herd 1 were maintained on a weekly reproductive health programme, while those in herd 2 were not subjected to gynaecological exploration. Surface features of the mesothelial cells of the reproductive tract and adjacent ligaments, and the oviductal mucosa were explored by SEM observation of tissue specimens from each animal. Six cows in the intensive reproductive programme showed microscopic alterations of the peritoneal surface. Strands were observed in the oviducts and adjacent ligaments in five of these cows. These strands, composed of filaments covered with mesothelial cells, were probably adhesions. Cells with abundant vacuoles on their surface were detected in the mesothelium corresponding to three animals, two of which also showed microscopic strands. No peritoneal surface alterations were observed in the cows from herd 2. No oviductal mucosal modifications were detected in either group. These findings suggest that intensive reproductive programmes based on rectal palpation may increase the risk of peritoneal surface alterations in the cow, but effects on reproductive physiology are unlikely.

Animals↗

Experimental diabetes induces functional and structural changes in the peritoneum.

BACKGROUND: Peritoneal dialysis (PD) is an established renal replacement therapy in diabetic patients, but the influence of diabetes on the peritoneal membrane (PM) remains debated. We have used functional, biochemical and molecular studies in vivo and in vitro to substantiate the changes induced by diabetes and hyperglycemia in the PM. METHODS: Peritoneal equilibration tests were performed 2, 4, and 6 weeks after induction of diabetes with streptozotocin (STZ) in rats. Morphological analyses, determination of nitric oxide synthase (NOS) activities, and expression studies for NOS isoforms and advanced glycation end products (AGE) were performed in parallel. Additional studies were conducted in diabetic rats treated with insulin, non-diabetic rats fed with urea, and cultured bovine aortic endothelial cells (BAEC). RESULTS: In comparison with controls, diabetic rats were characterized by: increased permeability for small solutes and decreased sodium sieving; capillary proliferation; increased endothelial NOS (eNOS) and AGE immunoreactivity; up-regulation of eNOS and down-regulation of neuronal NOS; and increased NOS activity in the PM. The changes, which culminated at week 6, were prevented by chronic insulin treatment in diabetic rats. In contrast to hyperglycemia, hyperosmolality alone did not induce functional or structural changes in the PM. Studies in BAEC showed that high glucose incubation led to increased activity and expression of eNOS, a prerequisite for vascular proliferation. CONCLUSIONS: These data demonstrate that chronic hyperglycemia is associated with functional and structural changes in the peritoneum that parallel with selective regulation of NOS isoforms and AGE deposits. The alterations are prevented by insulin treatment, which suggests that adequate control of diabetes can preserve PM integrity in diabetic patients prior to PD.

Animals↗

Selective depletion of fibroblasts preserves morphology and the functional integrity of peritoneum in transgenic mice with peritoneal fibrosing syndrome.

BACKGROUND: A peritoneal fibrosing syndrome (PFS) can progressively reduce peritoneal ultrafiltration during chronic peritoneal dialysis in patients with renal failure. The pathogenesis of PFS is unclear and the role of peritoneal fibroblasts has not been evaluated experimentally. METHODS: We followed the fate of fibroblasts producing PFS in a mouse model using fibroblast-specific protein 1 (FSP1) as a marker. PFS was induced by daily peritoneal infusions of chlorhexidine gluconate (CHG) saline into transgenic mice expressing the thymidine kinase (Delta tk) gene under the control of the FSP1 promoter (FSP1.Delta tk mice). To demonstrate the role of fibroblasts in PFS, we treated these FSP1.Delta tk mice with a nucleoside analogue to induce DNA chain termination and fibroblast death. RESULTS: Mice receiving peritoneal infusions of CHG saline every other day for 2 weeks developed increasing numbers of FSP1+ fibroblasts in the subserosal layers of the visceral peritoneum. Mac-3+ monocytes (macrophages) subsequently accumulated over the next 2 weeks in association with increased deposition of type I collagen and increased endothelial vascularity (CD31+) in these subserosal tissues. Since these peritoneal fibroblasts expressed monocyte chemoattractant protein-1 (MCP-1), heat shock protein 47 (HSP47), and vascular endothelial growth factor (VEGF), we suspect they were partially responsible for macrophage recruitment, matrix production, and the neoangiogenesis in the subserosal tissue. Treatment of PFS in FSP1.Delta tk transgenic mice with a nucleoside analogue selectively reduced the numbers of peritoneal fibroblasts and attenuated the attendant changes in peritoneal histology. Rescuing the peritoneal membrane from chronic thickening and neoangiogenesis by reducing the number of fibroblasts also preserved ultrafiltration. CONCLUSION: Peritoneal fibroblasts play a pivotal role in PFS, and their deletion using a fibroblasts-specific transgene was effective in preventing peritoneal fibrogenesis.

Animals↗

Localization of imidazolone in the peritoneum of capd patients: a factor for a loss of ultrafiltration.

The presence of dicarbonyl compounds, potent precursors of advanced glycation end products (AGEs), has been recognized in unused peritoneal dialysis (PD) fluids. Accumulation of AGEs has been implicated in the alteration of peritoneal membrane properties during continuous ambulatory peritoneal dialysis (CAPD) therapy. To determine whether imidazolone, an AGE specifically derived from 3-deoxyglucosone (3-DG), contributes to a decrease in ultrafiltration (UF) capacity of the peritoneal membrane in CAPD patients, we immunohistochemically evaluated the localization of imidazolone in peritoneal tissues from CAPD patients. Mesothelial thickening in the peritoneum was found in six of seven CAPD patients. Imidazolone distinctly accumulated in peritoneal tissues of CAPD patients, whereas it was hardly detected in those of patients with nonrenal disease. CAPD patients with a low UF capacity showed more extensive peritoneal deposition of imidazolone and more pronounced mesothelial thickening than those with a normal UF capacity. A CAPD patient with sclerosing peritonitis showed the most abundant localization of imidazolone among all CAPD patients. Gas chromatography/mass spectrometry showed that unused PD fluids contained high 3-DG concentrations (mean, 34.6 +/- 14.1 [SD] microgram/mL). In conclusion, the accumulation of imidazolone was noted in peritoneal tissues of CAPD patients, which preceded a decrease in UF capacity. Imidazolone modification may alter the quality of peritoneal membranes, presumably leading to a loss of UF and finally the development of sclerosing peritonitis.

Epithelium↗