A randomized, controlled pilot study of the safety and efficacy of 4% icodextrin solution in the reduction of adhesions following laparoscopic gynaecological surgery

BACKGROUND: Adhesion-related readmissions are frequent sequelae to gynaecological surgery. Attempts to prevent adhesions by separating healing peritoneal surfaces include site-specific barriers and hydroflotation by instilled solutions. Rapid absorption limits the effectiveness of solutions such as Ringer's lactated saline (RLS). This pilot study assessed the safety, tolerability and preliminary effectiveness of a non-viscous, iso-osmolar solution of 4% icodextrin, an alpha-1,4 glucose polymer with prolonged intraperitoneal residence, in reducing adhesions after laparoscopic gynaecological surgery. METHODS: Women aged > or = 18 years, requiring laparoscopic adnexal surgery (n = 62), were entered into a randomized, open-label, assessor-blinded, multicentre study to compare 4% icodextrin with RLS. Treatments were coded in blocks of four with equal randomization to each group, and pre-allocated to consecutively numbered patients. At least 100 ml per 30 min was used for intra-operative lavage, with 1 l instilled post-operatively. Per protocol analysis included all eligible patients (n = 53); reformation analysis required one or more baseline adhesion (n = 42). Incidence, extent and severity of post-operative adhesions were assessed at second-look laparoscopy after 6-12 weeks. Procedures were video-taped for third party, blinded assessment. RESULTS: Safety and tolerability (laboratory variables, adverse events, clinical follow-up) were good with no difference between treatments. A shift analysis of incidence-ranked adhesions (n = 53) showed apparent improvements in more patients with icodextrin than RLS (37 versus 15%; not significant). Adhesion score reduction (n = 42) was more frequent in icodextrin- than RLS-treated patients: incidence (52 versus 32%), extent (52 versus 47%), and severity (65 versus 37%). Despite greater baseline adhesions, median reformation was less after icodextrin (24%) than RLS (60%). The pilot study group sizes were not powered for statistical significance. CONCLUSIONS: In this preliminary study, 4% icodextrin lavage plus instillation was well tolerated and reduced adhesion formation and reformation following laparoscopic gynaecological surgery. A Phase III pivotal study is currently in progress.     

Cross-linked hyaluronate hydrogel prevents adhesion formation and reformation in mouse uterine horn model

The aim of this study was to evaluate the efficacy of cross-linked hyaluronate hydrogel (HA gel) as an adjuvant for postoperative adhesion prevention, in a mouse uterine horn model. In experiment 1 uterine horns were abrased with iodine. HA gel was applied to the injured surface before closure in the treatment group. In experiment 2, after injuring the uterine horns, three stitches were placed at equal distances around the uterine horns to appose the injured medial surfaces of the two horns during healing. HA gel was inserted between the uterine horns in the treatment group. In experiment 3 prevention of adhesion reformation was assessed. After lysis of adhesions that were induced as in experiment 2, HA gel was introduced between the serosal surfaces of apposing uterine horns. Untreated animals served as controls in each experiment. Statistical analysis was carried out using Student's t-test. The adhesion score was significantly lower in the HA gel group on the 14th day compared with controls in all the experiments: in experiment 1, 0.3 +/- 0.4 versus 1.7 +/- 1.2; in experiment 2, 0.9 +/- 1.0 versus 2.6 +/- 0.5; and in experiment 3, 1.5 +/- 0.9 versus 2.2 +/- 0.6 respectively. Cross-linked HA gel significantly reduced de-novo adhesions (P< 0.03) and adhesion reformation (P < 0.03).     

Reduction of post-surgical adhesions with ferric hyaluronate gel: a European study

BACKGROUND: The objective of this study was to assess the safety and efficacy of a 0.5% ferric hyaluronate gel, in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy, with a planned 'second-look' laparoscopy. METHODS: The study was a randomized (by computer-generated schedule), third party blinded, placebo-controlled, parallel-group design conducted at five centres in Europe. Females aged 18-46 years received 300 ml ferric hyaluronate (n = 38) or lactated Ringer's (n = 39) as an intraperitoneal instillate at the completion of surgery. At second-look 6-12 weeks later, the presence of adhesions was evaluated at 24 abdominal sites. RESULTS: Patients treated with ferric hyaluronate had significantly fewer adhesions compared with controls. When adhesions formed, they were significantly less extensive and less severe in the treated group. The American Fertility Society score for adnexal adhesions was reduced by 69% in the treatment group compared with controls. The safety profile of ferric hyaluronate-treated patients was comparable with those treated with lactated Ringer's solution. CONCLUSIONS: In conclusion, ferric hyaluronate was safe and highly efficacious in reducing the number, severity and extent of adhesions throughout the abdomen following peritoneal cavity surgery.     

Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study

BACKGROUND: A prospective, randomized, controlled study was performed to assess the efficacy of auto-crosslinked hyaluronic acid (ACP) gel to prevent the development of de-novo intrauterine adhesions following hysteroscopic surgery. METHODS: One hundred and thirty-two patients with a single surgically remediable intrauterine lesion (myomas, polyps and uterine septa, subgroups I-III) completed the study. Patients were randomized to two different groups: group A underwent hysteroscopic surgery plus intrauterine application of ACP gel (10 ml) while group B underwent hysteroscopic surgery alone (control group). The rate of adhesion formation and the adhesion score was calculated for each group and subgroup 3 months after surgery. RESULTS: Group A showed a significant reduction in the development of de-novo intrauterine adhesions at 3 months follow-up in comparison with the control group. Furthermore, the staging of adhesions showed a significant decrease in adhesion severity in patients treated with ACP gel. CONCLUSIONS: ACP gel significantly reduces the incidence and severity of de-novo formation of intrauterine adhesions after hysteroscopic surgery.     

Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective,randomized, controlled study

BACKGROUND: A prospective, randomized, controlled study was performed to assess the efficacy of auto-cross-linked hyaluronic acid (ACP) gel in preventing the development of intrauterine adhesions following hysteroscopic adhesiolysis. METHODS: Ninety-two patients with irregular menses and intrauterine adhesions referred to the Hysteroscopic Unit of the University of Naples "Federico II". Patients were randomized to two different groups. Group A were randomized to hysteroscopic adhesiolysis plus intrauterine application of ACP gel (10 ml) and group B were randomized to operative hysteroscopy alone (control group). Baseline adhesion scores were calculated for each patient and at 3 months after surgery. RESULTS: Group A showed a significant decrease in intrauterine adhesions at 3 months follow-up in comparison with the control group. Staging of adhesions showed a significant decrease in adhesion severity in patients treated with ACP gel. CONCLUSIONS: ACP gel significantly reduces the development of intrauterine adhesions postoperatively and its use is likely to be associated with a reduction of severe adhesions.     

Inhibition of chemokines prevents intraperitoneal adhesions in mice

BACKGROUND: The present study evaluates the efficacy of a broad-spectrumchemokine inhibitor, NR58-3.14.3, in the prevention of adhesionformation after i.p. surgery in mice. METHODS: A total of 110eight week old female Balb/c mice underwent laparotomy. Fortyanimals were randomly assigned to receive daily i.p. injectionsof either vehicle (control) or NR58-3.14.3. Time-course of adhesionformation was assessed. A titration of NR58-3.14.3 was conductedfor i.p. and s.c. administrations. The effectiveness of a singleintra-operative dose of NR58-3.14.3 was evaluated. Number, extent,location and type of adhesions were recorded. Immunohistochemistryof adhesions was done with leukocyte common antigen, CD45. RESULTS:Adhesion scores peaked on post-operative days 6–8. Onboth days 6 and 8, there were smaller adhesion size and lowercumulative adhesion scores in NR58-3.14.3-treated group. Moreover,on day 8, there were significantly fewer adhesions in NR58-3.14.3-treatedgroup compared to controls. The least effective dose for i.p.administration of NR58-3.14.3 was 0.45 mg/animal. Subcutaneousand single intra-operative i.p. administrations were also effectivein the prevention of i.p. adhesions. Although NR58-3.14.3 decreasedthe number of CD45⁺ inflammatory cells in the adhesions by 22.5%compared to control group, this was not significant. CONCLUSIONS:Our results show that this broad-spectrum chemokine inhibitorprevents post-operative adhesions in mice and may have a potentialclinical use.     

Effect of melatonin in the prevention of post-operative adhesion formation in a rat uterine horn adhesion model

BACKGROUND: Our main aim was to investigate the effects of melatonin (ME), possibly the most powerful free-radical scavenger, on the prevention of i.p. adhesion formation in rat uterine horn. Our secondary aim was to determine whether different methods of administration of ME were beneficial. METHODS: Animals were randomly assigned into seven groups, each consisting of 13 rats. Measured serosal injury was created using a standard technique. While control and two sham groups were not given ME, two of the remaining four groups were given a single dose of 10 mg/kg (2 mg) of ME i.p. immediately after injury and 30 min prior to injury respectively. In the two other groups, ME treatment was continued daily for 5 days. All animals were killed 2 weeks after surgery and adhesions were determined and scored by a examiner blinded to the test. RESULTS: The extent, severity and total scores of adhesion were found to be significantly reduced in all of the ME treatment groups when compared with control and sham groups. There were no statistically significant differences between the treatment groups. CONCLUSIONS: This study showed that even single dose ME therapy was effective in the prevention of post- operative i.p. adhesion formation.     

The mouse as a model to study adhesion formation following endoscopic surgery: a preliminary report.

Our aim was to investigate the feasibility of a mouse model to study adhesion formation following endoscopic surgery. Following preliminary studies to establish anaesthesia and pneumoperitoneum pressure, a prospective randomized study was carried out to investigate the effect of CO2 pneumoperitoneum on postoperative adhesions. In group I (control group), the duration of pneumoperitoneum was shorter than 5 min. In groups II, III and IV, pneumoperitoneum was maintained for 60 min without flow, with a continuous low flow (1 ml/min) and a continuous high flow (10 ml/min) through the abdominal cavities of the mice using non-humidified CO2, respectively. Adhesions were scored after 7 days by laparotomy. The total adhesion scores were 0.9 +/- 0.8 (n = 15) in control group, 2.4 +/- 0.8 (n = 15) (P < 0.001 versus control group) in group II with no flow, 2.6 +/- 1.3 (n = 15) (P < 0.001 versus control group) in group III with a continuous low flow and 4.3 +/- 0.9 (n = 15) (P < 0.001 versus control group and P < 0.001 versus group II and III) in group IV with a continuous high flow. In conclusion, the mouse can be used as a model to study adhesion formation following endoscopic surgery. Duration of CO2 pneumoperitoneum is a co-factor in adhesion formation.     

Adhesion preventive effect of hyaluronic acid after intraperitoneal surgery in mice.

Prevention of intraperitoneal adhesion after gynaecological surgery is essential for maintaining postoperative fertility. In this study, the adhesion prevention effect was examined of a hyaluronic acid (HA) solution obtained from the fermentation method and having a molecular weight of 1.9x10(6) with high viscosity. Laparotomy was conducted on female mice 7 weeks old, whose menstrual periods were synchronized by pregnant mare serum gonadotrophin (PMSG) to injure the uterine horn surface. Intraperitoneal adhesions were favourably formed in 91.7% of cases induced with iodine abrasion, compared with 50% induced by electrosurgery. Intraperitoneal administration of HA was evaluated for its effect on the prevention of adhesions made by iodine abrasion. Adhesion prevention effects of HA were observed at concentrations of 0.3, 0.5, 0.75 and 1.0%, among which the most pronounced effect was with the use of a 0.3% solution (92.3% of cases). Compared with the control group adhesion score of 2.0 +/- 0. 8, significant decreases in adhesion scores were observed at all concentrations. HA with a molecular weight of 1.9x10(6) was recognized to have a definitive prevention effect on postoperative adhesions in mice after laparotomy and is considered to be a prospective material for future clinical use.     

Development of a novel glucose polymer solution (icodextrin) for adhesion prevention: pre-clinical studies

Intra-abdominal adhesion formation causes significant post-operative morbidity. Controlled studies using animal models have been carried out to assess the tolerability and preventive efficacy of icodextrin solution (a biodegradable, biocompatible, glucose polymer). Reduction of adhesion formation was first evaluated in a rabbit double uterine horn model, applying 10-75 ml of 7.5 and 20%, or 50 ml of 2.5-20% icodextrin solution post-operatively. Significant increases in adhesion free sites (P < 0.005) were observed with volumes > or =25 ml, and at concentrations > or =4%. Efficacy of 50 ml 4 and 20% icodextrin was then evaluated both during and after surgery, demonstrating significant reductions in adhesion formation (P < 0. 002). In one study, intra- plus post-operative use of 4% icodextrin produced the greatest reduction of non-surgical site adhesions; in others, the post-operative effect was predominant. Post-surgical administration of 50 ml 4% icodextrin in a rabbit sidewall model also resulted in more adhesion-free animals, and a significant reduction (P < 0.001) in areas of adhesion formation and reformation. In a rat infection potentiation model, 4% icodextrin produced no difference in mortality, abscess formation or overall abscess score. These data suggest that 4% icodextrin offers a well-tolerated and effective means of reducing post-surgical adhesion formation.     

Human critical power-oxygen uptake relationship at different pedalling frequencies

Critical power (CP) is lower at faster rather than slower pedalling frequencies and traditionally reported in watts (W). Faster pedalling frequencies also engender a greater metabolic rate (VO2) at low work rates, but with progressive increases in power output, the initial difference in VO2 between fast and slower pedalling frequencies is reduced. We tested the hypothesis that CP represents a unique metabolic rate for any given individual which would be similar at different pedalling frequencies. Eleven collegiate athletes (five cross-country runners, END; six sprinters, SPR), aged 18-23 years, performed exhaustive rides at either 60 or 100 r.p.m. on separate days for the determination of the pedal rate-specific CP. The VO2 at CP (CP-VO2) was determined from an 8 min ride at the CP for each pedal frequency. The group mean CP was significantly lower at 100 r.p.m. (189 +/- 50 W) compared to 60 r.p.m. (207 +/- 53 W, P < 0.05). However, the group mean CP-VO2 values at 60 (2.53 +/- 0.60 l min(-1)) and 100 r.p.m. (2.58 +/- 0.53 l min(-1)) were not significantly different. Critical power was significantly higher in the END athletes (242 +/- 50 W at 60 r.p.m.; 221 +/- 56 W at 100 r.p.m.) compared to SPR athletes at both pedal frequencies (177 +/- 38 W at 60 r.p.m.; 162 +/- 27 W at 100 r.p.m., P < 0.05), but the CP-VO2 was not (P > 0.05). However, when the CP-VO2 was scaled to body weight, the END athletes had a significantly greater CP-VO2 (41.3 +/- 4.1 ml min(-1) kg(-1) at 60 r.p.m.; 40.8 +/- 5.5 ml min(-1) kg(-1) at 100 r.p.m.) compared to the SPR athletes at both pedal frequencies (27.7 +/- 4.6 ml min(-1) kg(-1) at 60 r.p.m.; 29.4 +/- 2.8 ml min(-1) kg(-1) at 100 r.p.m., P < 0.05). We conclude that CP represents a specific metabolic rate (VO2) which can be achieved at different combinations of power outputs and pedalling frequencies.     

The effect of rosiglitazone in the prevention of intra-abdominal adhesion formation in a rat uterine horn model

BACKGROUND: Effects of rosiglitazone in the prevention of adhesion formation were evaluated. METHODS: Eighty Wistar albino rats were randomly grouped into eight equally sized groups. A 2-cm segment of the antimesenteric surface of the right uterine horn was traumatized to form a standardized lesion, using bipolar cautery. A dose-response study was performed with 0.1, 0.3, 1 and 3 mg/kg/day rosiglitazone. Fifteen days later, adhesions were evaluated clinically and histopathologically. A time-response study was performed with 1 mg/kg/day rosiglitazone (the minimum dose found to significantly affect adhesion formation). Rosiglitazone was given for 7 days post-operatively and results were compared with those of control and the 15-day group (time-response). In all these studies, rosiglitazone was orally administered 3 days before the operation and continued post-operatively. In two further experimental groups, rosiglitazone was only administered pre-operatively or post-operatively. RESULTS: Approximately 1 mg/kg/day rosiglitazone was found to reduce adhesion scores both clinically and histopathologically. Duration of treatment was also found to affect the extent of adhesion formation. However, giving rosiglitazone either just pre-operatively or post-operatively did not significantly reduce adhesion formation. CONCLUSION: Rosiglitazone with peroxisome proliferator-activated receptor (PPAR)-gamma agonist activity reduced the formation of i.p. adhesion possibly by reducing the initial inflammatory response and the subsequent exudation in this study.     

Reduction of postoperative adhesions with an auto-crosslinked hyaluronan gel in gynaecological laparoscopic surgery: a blinded, controlled, randomized, multicentre study

BACKGROUND: Following myomectomy, postoperative adhesions occur in many patients with adverse effects on fertility. This study investigated the applicability, safety and efficacy of an auto-crosslinked hyaluronan gel in preventing adhesion formation after laparoscopic myomectomy. METHODS: Fifty-two patients aged 22-42 years, undergoing surgery at four centres, were randomly allocated to receive either the gel or no adhesion prevention. The incidence and severity of postoperative adhesions were assessed laparoscopically after 12-14 weeks in a blinded, scored fashion. The primary efficacy variable was the presence/absence of postoperative adhesions at second-look. RESULTS: A nonsignificantly higher proportion of patients receiving the gel were free from adhesions (13 of 21; 62%) compared with control patients (9 of 22; 41%), with a statistically significant difference between the severity of uterine adhesions at baseline and at second-look (0.3 +/- 0.9 versus 0.8 +/- 1.0, P < 0.05). In subjects undergoing myomectomy without concomitant surgery, the proportion of adhesion-free patients was 8 of 12 (67%) and 4 of 11 (36%) (not significant) in the gel and control groups, respectively, with a significant difference in the mean severity scores (P < 0.05). In subjects without uterine adhesions before myomectomy, 12 of 18 (67%) and 8 of 20 (40%) patients in the gel and control groups, respectively were adhesion-free (not significant), with a significant difference in the severity of uterine adhesions (P = 0.05). CONCLUSIONS: Our results suggest that the auto-crosslinked hyaluronan gel may have a favourable safety profile and efficacious antiadhesive action following laparoscopic myomectomy.     

Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND. Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment. METHODS. We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group). RESULTS. The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001). CONCLUSIONS. In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.     

Clinical evaluation of 0.5% ferric hyaluronate adhesion prevention gel for the reduction of adhesions following peritoneal cavity surgery: open-label pilot study

The objective of this study was to assess the safety and to make a preliminary assessment of the efficacy of 0.5% ferric hyaluronate adhesion prevention gel in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy, with a planned 'second-look' laparoscopy. The study was a randomized, open-label, placebo- controlled, parallel-group design in patients desirous of fertility at the Women's and Children's Hospital, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California. Female patients aged 24 to 41 years received 300 ml 0.5% ferric hyaluronate adhesion prevention gel or lactated Ringer's solution as an intraperitoneal instillate at the completion of the laparotomy procedure. At second-look laparoscopy 4-12 weeks after the laparotomy, the presence of adhesions was evaluated. Haematology and serum chemistry were determined throughout the study interval. All patients tolerated the procedures well and did not manifest any serious adverse events. At second-look laparoscopy, patients treated with 0.5% ferric hyaluronate adhesion prevention gel had significantly fewer adhesions than control patients. When adhesions did form, they were significantly less extensive and less severe in patients who received 0.5% ferric hyaluronate adhesion prevention gel. In conclusion, 0.5% ferric hyaluronate adhesion prevention gel was safe and highly efficacious in the reduction of the number, severity and extent of adhesions throughout the entire abdomen following peritoneal cavity surgery.      

Lower long-term efficiency of intradermal hepatitis B vaccine compared to the intramuscular route in hemodialysis patients

Intramuscular (i.m.) and Intradermal (i.d.) vaccination against hepatitis B (HB) are efficient in hemodialysis patients. We retrospectively analysed the response of 32 patients during 48 consecutive months and compared the results of the two vaccination routes using the recombinant vaccine (Engerix, SKB). Thirteen patients were vaccinated with 5 mcg i.d. every 2 weeks (total 8 doses), plus an i.m. dose on month (M) 12 (group A). Nineteen patients (group B) were vaccinated with 4 i.m. doses of 20 mcg each, on months M0, 1, 2 and 12. HB antibodies were measured on M5, M11, M13, M24, M36 and M48. An additional 20 mcg i.m. dose was given with titers below 10 mIU/ml. Seroconversion, seroprotection and antibody levels were equivalent in both groups up to M13; with the exception of seroconversion rates, a significantly different response was observed afterwards (A/B, in mIU/ml): M5: 399 +/- 107 vs 342 +/- 69, M13: 536 +/- 118 vs 673 +/- 61, M24: 278 +/- 94 vs 595 +/- 81, P=0.02, and M48: 68 +/- 29 vs 565 +/- 92, P=0.003. Early HB(S)AB levels did not correlate with those found four years later in both groups. An additional booster dose was given 8 times in 4 group A patients (1-3 doses/patient) and 3 times in 1 group B patient. Immune response to HB vaccine in hemodialysis patients is initially equivalent by both immunization routes. Late antibody titers were found significantly lower in i.d. immunization with more frequent booster doses needed.     

Blood serum levels of vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) in diabetic retinopathy

BACKGROUND: Interaction between cells via intimate cell-cell contact is facilitated by a cell surface molecules, termed adhesion molecules. The aim of the study was to evaluate the blood serum concentration of soluble forms of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) in patients with type 1 diabetes mellitus without and with diabetic retinopathy. MATERIALS AND METHODS: The study was performed in 75 patients with type 1 diabetes mellitus, 35 without retinopathy (group 1) and 40 with retinopathy (group 2). Soluble forms of VCAM-1, ICAM-1 and ELAM-1 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum concentration of sICAM-1 and sELAM-1 were significantly elevated and the concentration sVCAM-1 was elevated but not significantly in diabetic patients when compared with control subjects. There was a significant difference in VCAM-1 concentrations between the control group and group 2 (965.9 +/- 229.0 vs. 1283.7 +/- 387.6 ng/ml, p < 0.05) and between group 1 and group 2 (1115.0 +/- 285.5 vs. 1283.7 +/- 387.6 ng/ml, p < 0.05). There were significant differences in sICAM-1 concentrations between the control group and group 1 (p < 0.05) and between the control group and group 2 (p < 0.05). Where was no significant difference in sICAM-1 concentration between group 1 and 2 (405.2 +/- 135.9 vs. 443.1 +/- 112.7 ng/ml, p = 0.08). ELAM-1 concentration was significantly elevated in group 2 (120.5 +/- 49.3 ng/ml) when compared with the control group (51.7 +/- 18.1 ng/ml, p < 0.005) and with group 1 (81.2 +/- 27.7 ng/ml, p < 0.05). CONCLUSIONS: The correlations found between sVCAM-1, sICAM-1 and sELAM-1 and the presence of retinopathy suggest that cellular adhesion and neovascularization may be linked processes.     

N-acetylcysteine exerts protective effects and prevents lung redox imbalance and peroxynitrite generation in endotoxemic rats

The aim of this study was to determine in endotoxemic rats the effects of N-acetylcysteine on lung redox imbalance and plasma peroxynitrite generation. Eighty male Wistar rats were divided in two sets of five experimental groups. Six hours after vehicle (Control group: isotonic NaCl sterile solution i.p.; n=7), lipopolysaccharide (LPS group: 1 mg/Kg i.p.; n=8), N-acetylcysteine plus LPS (NAC+LPS group, n=8), NAC plus the nitric oxide synthesis inhibitor N(w)-nitro-L-arginine methyl ester plus LPS (NAC+NAME+LPS group; n=8), or NAME plus LPS (NAME+LPS group; n=9), arterial blood and lung samples were taken from each animal under sodium pentobarbital anesthesia. In five additional groups treated as described above, in vivo plasma oxidation of dihydrorhodamine (DRH) 123 to rhodamine (RH)123 was measured as index of peroxynitrite formation. LPS treated rats presented increased plasma lactate, thrombocytopenia and both, decreased reduced thiols and increased lipid peroxidation in lung tissue. Moreover, LPS produced increments in plasma concentration of nitrites/nitrates and DRH 123 oxidation. Pretreatment with NAC prevented all these changes induced by LPS except the increment in plasma concentration of nitrites/nitrates. The protective effects seen in LPS rats pretreated with NAC were not observed in the NAC+NAME+LPS group. In conclusion, the results of this study show that in endotoxemia induced by LPS in rats, NAC produces protective effects on lung redox balance and prevents peroxynitrite anion generation.     

Effects of five different barrier materials on postsurgical adhesion formation in the rat

Postsurgical adhesion formation is a significant clinical problem within every surgical specialism. Due to the problems that adhesions cause, a wide variety of adjunctive treatments to prevent the formation and reformation of adhesions have been proposed. One of the modalities that has been studied extensively and that has been showing the most promising results is the so-called barrier method. The purpose of the present study was to compare the efficacy of five of these barrier materials in the prevention of postsurgical adhesion formation in a standardized rat adhesion model. It was concluded that no beneficial effect of Ringer's lactate on adhesion formation was seen. Significant reductions (P < 0.0001) in adhesion percentages compared to control animals were seen with Polyactive((TM)), PRECLUDE Peritoneal Membrane((TM)), Seprafilm((TM)) and Tissucol((TM)), but only PRECLUDE Peritoneal Membrane and Seprafilm significantly reduced adhesions (P < 0.01) when the barrier-treated peritoneal defects were compared with contralateral control-side peritoneal defects. The results of our study suggest that Seprafilm and PRECLUDE Peritoneal Membrane are superior to Tissucol and Polyactive in preventing adhesion formation. When Polyactive was still attached to the site of application during the second laparotomy, similar results to Seprafilm and PRECLUDE Peritoneal Membrane were seen. Future studies on the efficacy of a material to decrease adhesion formation should always include a comparison of several control materials in the same model. Our study indicates that Seprafilm or PRECLUDE Peritoneal Membrane might be used as standards of control.     

Prevention of post-surgical adhesion formation using aspirin in a rodent model: a preliminary report

Pelvic adhesions are one of the major factors which significantlyand adversely affect surgery outcome due to intra-and postoperativemorbidity and reduce future female fertility. Using a rodentmodel, we evaluated the efficacy of aspirin, a non-steroidalanti-inflammatory drug, in the prevention of adhesion formation.A total of 72 female Wistar rats received a standardized primarytraumatic lesion to the right uterine horn. They were randomlydivided into eight groups: group I (control) had no treatmentand group II received a single pre-operative 0.70 mg aspirin.All the succeeding groups (III-VIII) received aspirin in dosesof 0.35, 0.70, or 1.40 mg every 6 h for either 48 or 96 h inaddition to the pre-operative aspirin (0.70 mg). All animalswere killed 4 weeks later and adhesions were assessed usinga modified adhesion scoring scale. The lowest adhesion scorewas found in the group treated with 0.35 mg of aspirin for 96h, and the highest was found among the groups treated with either0.70 or 1.40 mg for 48–96 h respectively (P < 0.05).These results are in line with the hypothesis that administrationof a low dose of aspirin selectively inhibits the productionof thromboxane A₂, whereas basal prostacyclin biosynthesis ispreserved. This phenomenon might contribute to reducing postoperativeadhesion formation in a rat model. Thus, future studies intothe prevention of adhesion formation may require the additionaluse of a non-steroidal anti-inflammatory drug, for which aspirindeserves further attention, before extrapolation into humantherapy.