Succinylated Gelatin Research Articles

A Case of Kounis Syndrome Caused by Anaphylaxis During Surgery

Kounis syndrome is a hypersensitivity coronary disorder associated with several triggers, such as drugs, foods, environmental, coronary stents and other factors. It was originally proposed by the Greek cardiologist Nicholas Kounis in 1991. Kounis syndrome is a life-threatening and challenging emergency disease, which is constantly being recognized and studied. It is a disease that is constantly being recognized and Kounis syndrome can be classified into three types, involving coronary artery spasm, plaque rupture or stent thrombosis respectively. Most patients with coronary artery spasm caused by allergies can recover completely after active treatment, and the prognosis is good. If not, it may cause severe myocardial damage and even myocardial infarction, which threatens the patient's life. In our case, a 56-year-old female patient was scheduled to undergo right pelvic resection. A few minutes after the start of intravenous succinylated gelatin infusion, she was experienced a decrease in heart rate, blood pressure, oxygen saturation and ST elevation on 2-lead. An anaphylactic reaction was suspected after rapid differential diagnosis and gradually recovered with treatment. In this context, a rapid differential diagnosis and a highly suspicious become essential, because the management of Kounis syndrome is different from the traditional acute coronary syndrome. Kounis syndrome requires simultaneous diagnosis and treatment of both allergic reaction and acute coronary syndrome based on their manifestations and risk factors. This case describes the onset, development, and recovery of Kounis syndrome in this patient in detail, and illustrates the classification, pathophysiology, and treatment of Kounis syndrome. It is hoped that through the management of this case, the occurrence of Kounis syndrome can be rapidly identified and treated accordingly so that avoiding disaster for patients.

Hemodynamic efficacy and safety of using modified gelatin solution and polyhydric alcohol solution for fluid resuscitation of patients with septic shock

Objective ‒ to compare the hemodynamic effects and safety of the infusion of succinylated gelatin solution, sorbitol-containing solution, and 0.9 % normal saline (0.9 % sodium chloride), analyze their effect on the treatment of septic shock and mortality.Materials and methods. A prospective randomized clinical trial that included 94 adult patients with an active surgical infection and septic shock was conducted. There were 34 (36.2 %) male and 60 (63.8 %) female patients aged between 19 and 96 years, mean age was (66.51 ± 17.06) years. An appropriate solution in a volume of 500 ml was used for resuscitation, then hemodynamic and other clinical and laboratory parameters were monitored.Results. There was no significant difference in mean arterial pressure (MAP) between the 3 groups until the 40th minute (p>0.05). At the 45th minute MAP in the NS group differed only from MAP in the Gel group (p=0.007). At the 50th minute MAP in the NS group did not differ from the baseline (p=0.139). From the 50th minute to 2 hours, MAP in the Gel and Sorb groups was higher than in the NS group in all measurements (p<0.05). There was no statistically significant difference in heart rate (HR) in any measurement (p>0.05). Cardiac output (CO) did not differ up to the 30th minute (p>0.05), at the 35th minute, CO differed only between Gel and NS groups (p=0.019), from the 40th minute to 2 hour CO in Gel and Sorb groups were significantly higher than in NS group in all measurements (p<0.05). Oxygen delivery (DO2) also did not differ up to the 30th minute (p>0.05), from the 35th minute to the 45th minute a significant difference was found only between Gel and NS groups (p<0.05), from the 50th minute to 2 hour DO2 in Gel and Sorb group was significantly higher than in NS group in all measurements (p<0.05). After infusion of the gelatin-containing solution and sorbitol-containing solution, the acid-base balance of the blood improved significantly. The dose of gelatin-containing and sorbitol-containing solutions applied in this study was safe for the renal function of the patients with septic shock. However, it is possible that a decrease in blood fibrinogen concentrations may be associated with the use of a gelatin-containing solution. Significant improvement in the Glasgow Coma Scale scores was observed only in patients in the group receiving the sorbitol-containing solution. The difference in 28-day mortality between the groups was not statistically significant (p=0.993).Conclusions. In our observations, when using these three types of solution in patients with septic shock, hemodynamic effects up to the 40th minute did not differ between groups. From the 40th minute to 2 hour, the volemic effect of 4 % succinylated gelatin solution and balanced polyionic solution with 6 % sorbitol was significantly better, compared to the 0.9 % sodium chloride solution. The volume of solutions used in these three groups did not affect renal function in patients with septic shock. The amount of balanced polyionic solution used with 6 % sorbitol and 0.9 % sodium chloride solution did not affect blood coagulation function. But the use of 4 % succinyl gelatin solution reduced the concentration of fibrinogen in the blood. After infusion of the gelatin-containing solution with buffer formulations and sorbitol-containing solution with buffer formulations, the acid-base status of the blood was significantly improved compared to 0.9 % sodium chloride solution. Infusion of the gelatin-containing solution and 0.9 % sodium chloride solution did not affect the Glasgow coma score in patients. After infusion of the sorbitol-containing solution, patients’ consciousness was improved by this scale. The 28-day mortality did not differ significantly between groups.

Experimental justification of the method of endoscopic hemostasis

To study the possibility and effectiveness of using succinylated gelatin (SG) for injecting endoscopic hemostasis. Material and methods. 70 albino non-linear rats. 0.5 ml of the solution has been injected into the anterior wall of the stomach with a syringe after laparotomy. A mixture of 0.9 % NaCl solution and epinephrine hydrothartrate (1.8 mg/1 ml) has been used in a ratio of 1:20 for the control group (35 animals). A mixture of a solution of SG (40 mg/1000 ml of injection water) and epinephrine hydrothartrate (1.8 mg/1 ml) in a ratio of 1:20 for the experimental group (35 animals). Right after the injection and in 1, 3, 6, 12 hours, after laparotomy, the stomach wall has been taken for histological examination, during which the thickness of the stomach wall (TSW) has been determined. Results. As soon as the injection has been given, the TSW in animals of both groups hasn`t differed significantly. The TSW has significantly increased in both of the groups, and the parameters of indicators in the experimental group have significantly raised in 1 h after the injection. In 3, 6, and 12 hours, the TSW in both groups has been decreasing. The parameters of indicators in the experimental group of animals have been significantly higher than in the control one all the time during the study. The indicators have barely differed from the initial ones in the control group 12 hours later, whereas in the experimental one they have been significantly higher. Histological studies have shown that the structure of stomach tissues in both groups hasn`t varied. The SG injection has not caused any negative effects on the tissues of the stomach wall. The thickness of the submucosa hasn`t been much modified right after the injection. The thickness (26.95±5.34 microns) has increased in the experimental group 12 hours later than in the control one (15.45±4.38 microns, p<0.01). Most of the vessels of the experimental group have remained compressed 12 hours later, whereas the diameter of the vessels of the control group has been growing. Conclusions. 1. The TSW hasn`t differed right after the injection (a mixture of 0.9 % NaCl and epinephrine solution and a mixture of SG and epinephrine solution) into the stomach wall. 2. 1 h later after the injection, the TSW has increased and its parameters after injection of a mixture with SG have been significantly higher. 3. In 3,6,12 h and later on, the TSW has been gradually reducing and its parameters after injection of a mixture with SG have been significantly higher each time. The thickness of the submucosa and the degree of compression of the vessels have also been considerably higher. 4. No negative changes in the structure of stomach tissues after injection of the mixture with SG have been detected. This allows it to be used for performing endoscopic hemostasis by injection therapy in clinical conditions.

Successful outcomes of a new combined solution of hyaluronic acid, chondroitin sulfate and poloxamer 407 for submucosal injection: animal survival study.

Background and study aims Endoscopic resection requires use of submucosal injection. This study was conducted to assess efficacy and impact on early healing of hyaluronic acid combined with chondroitin sulfate and poloxamer 407 (Ziverel) when used as a solution for submucosal injection. Materials and methods Prospective and comparative study of gastric endoscopic mucosal resection (EMR) with three groups of two Yorkshire pigs. Six submucosal cushions were created in each animal by injecting 2 mL of Ziverel (Group 1) or succinylated gelatin (SG) (Group 2), enabling 12 EMR in each group. Submucosal cushions were created with Ziverel in Group 3, without resection. Electrosurgery unit settings were the same in all cases. EMR defects and injection sites were marked with clips. The animals were sacrificed 7 days later. EMR specimen size and duration of procedure were recorded. EMR specimens and EMR scars and injection sites were evaluated by a blinded pathologist. Results We successfully performed 24 EMR (15 en-bloc and 9 piecemeal, without differences between groups 1 and 2). Mean EMR specimen dimensions were significantly larger in Group 1 (median 19 mm, range 6 – 40 vs 16.6 mm, range 5‑25; P = 0.019), without changing the electrocautery unit settings. Blinded histopathologist assessment of EMR specimens showed less fibrosis in the submucosa and a trend to fewer cautery artifacts with Ziverel and did not identify any significant differences in early healing of resection sites. Conclusion The combination of Ziverel enables EMR and does not negatively affect early healing.

Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies.

BackgroundImprovement in drug accumulation in the lungs through inhalation administration and high expression of MMP2 and MMP9 in lung tumors have both been widely reported.MethodsMMP2/9-triggered-release micelles were constructed and in vitro and in vivo studies of inhalation administration against lung tumor carried out. Pluronic P123 (P123) was modified with GPLGIAGQ-NH2 (GQ8) peptide to obtain P123-GQ8 (PG). MMP2/9-triggered-release micelles were constructed using PG and succinylated gelatin (SG) and loading paclitaxel (Ptx). To study biodistribution of micelles, DiR encapsulated in micelles was dosed to rats via intravenous injection or inhalation before ex vivo imaging for detecting DiR quantity in lungs. And B16F10 lung cancer-bearing nude mice were chosen as animal models to evaluate in vivo efficacy of MMP2/9-triggered-release micelles.ResultsPtx-release efficiency from PG-SG-Ptx micelles was MMP2/9-concentration-dependent. For A549 cells, PG-SG-Ptx cytotoxicity was significantly greater (P<0.001) compared to P123-Ptx. Aerosol inhalation was chosen as the method of administration. In biodistribution experiment, DiR quantity in lungs was 5.8%±0.4% of that in major organs, while the ratio was 38.8%±0.5% for inhalation. For B16F10 lung cancer-bearing nude mice, the efficacy of inhalation of PG-SG-Ptx was significantly higher (P<0.001) than Taxol inhalation and injected PG-SG-Ptx. Inhaled PG-SG-Ptx also significantly inhibited the expression of Pgp in lung cancer.ConclusionInhalation of MMP2/9-triggered-release micelles increased tumor sensitivity to chemotherapeutics and reduced the toxicity of chemotherapy to healthy lung cells, which has great potential in lung cancer therapy.

Preparation and evaluation of gelling granules to improve oral administration.

We investigated the preparation of oral granules that are solid when stored and that will swell and gel via water absorption, to address problems experienced by patients when taking medication. Important physical properties of gelling granules include elasticity that is normally smooth, quick water absorption and swelling properties that allow easy swallowing. We selected gelatin (GEL), succinylated gelatin (SUC-GEL) and ι-carrageenan (CAR) as matrix polymers that can undergo gelation at room temperature or at cold temperatures. Saccharide and polyethylene glycol (PEG) were added to prepare the experimental granules. The best matrix gelling granule was SUC-GEL. When xylitol (XYL), sorbitol (SOR) and maltitol (MAL) were added, elasticity was improved, and PEG improved the granule's water absorption behavior, which is an important element involved in gelation. The best granules were prepared by selecting SUC-GEL as the matrix and adding a small amount of PEG and XYL in amounts equal to that of SUC-GEL.

Prevention of altered hemodynamics after spinal anesthesia: A comparison of volume preloading with tetrastarch, succinylated gelatin and ringer lactate solution for the patients undergoing lower segment caesarean section.

Background:Spinal anesthesia has replaced general anesthesia in obstetric practice. Hemodynamic instability is a common, but preventable complication of spinal anesthesia. Preloading the circulation with intravenous fluids is considered a safe and effective method of preventing hypotension following spinal anesthesia. We had conducted a study to compare the hemodynamic stability after volume preloading with either Ringer's lactate (RL) or tetrastarch hydroxyethyl starch (HES) or succinylated gelatin (SG) in the patients undergoing cesarean section under spinal anesthesia.Materials and Methods:It was a prospective, double-blinded and randomized controlled study. Ninety six ASA-I healthy, nonlaboring parturients were randomly divided in 3 groups HES, SG, RL (n = 32 each) and received 10 ml/kg HES 130/0.4; 10 ml/kg SG (4% modified fluid gelatin) and 20 ml/kg RL respectively prior to SA scheduled for cesarean section. Heart rate, blood pressure (BP), oxygen saturation was measured.Results:The fall in systolic blood pressure (SBP) (<100 mm Hg) noted among 5 (15.63%), 12 (37.5%) and 14 (43.75%) parturients in groups HES, SG, RL respectively. Vasopressor (phenylephrine) was used to treat hypotension when SBP <90 mm Hg. Both the results and APGAR scores were comparable in all the groups. Lower preloading volume and less intra-operative vasopressor requirement was noted in HES group for maintaining BP though it has no clinical significance.Conclusion:RL which is cheap, physiological and widely available crystalloid can preload effectively and maintain hemodynamic stability well in cesarean section and any remnant hypotension can easily be manageable with vasopressor.

Comparison of hydroxyethyl starch and succinylated gelatin in cadaver renal graft function in kidney- transplant recipients

Hydroxyethyl starch solution (HES) is increasingly used during kidney transplantation for compensation of hypovolemia. However, the advantages of HES remain unclear. This clinical trial compared the effect of administering 6% HES 130/0.4 and 4% succinylated gelatin (SG) for volume replacement on the rate of delayed graft function (DGF), the occurrence of sensitive markers of renal impairment, and peritransplantation indexes of hemodynamic stability. After exclusion, 71 patients aged 23 to 64 years who underwent cadaver kidney transplantation were enrolled. Of these, 36 received 6% HES 130/0.4 and 35 were given 4% SG for volume replacement. The rate of DGF; the levels of beta 2-microglobulin (β2-MG), alpha 1-microglobulin (α1-MG), blood urea nitrogen (BUN), and serum creatinine (sCr); and the peritransplantation urine volume were determined and used as primary investigative parameters. The HES group showed a significant postoperative decrease in serum β2-MG, BUN, and sCr. Postoperative urine levels of β2-MG and α1-MG also decreased significantly in patients who received HES (p < 0.001) and postoperative urine volume was significantly higher in the HES group as compared to the SG group (p = 0.0012). No significant hemodynamic stability differences were seen between patients who received HES or SG colloids; however, 6% hydroxyethyl starch 130/0.4 led to better recovery outcomes in patients who underwent cadaver kidney transplantation. Key words: Hydroxyethyl starch, succinylated gelatin, volume replacement, renal function, kidney transplantation.

BEYOND THE SNARE: TECHNICALLY ACCESSIBLE LARGE EN BLOC COLONIC RESECTION IN THE WEST: AN ANIMAL STUDY

Endoscopic submucosal dissection (ESD) and circumferential submucosal incision endoscopic mucosal resection (CSI-EMR) are techniques for en bloc excision of large sessile colonic lesions. Our aims were to compare the efficacy, safety and learning curve of colonic hybrid knife (HK) ESD versus CSI-EMR for en bloc excision of 50 mm diameter hemi-circumferential artificial lesions in a porcine model. Two separate 50 mm diameter areas of normal recto-sigmoid mucosa were marked out in each of ten pigs. One was excised with HK-ESD using succinylated gelatin (SG) submucosal injection. The other was isolated with CSI with the Insulated Tip Knife 2 followed by SG submucosal injection then EMR with a large snare. Euthanasia and colectomy was performed at 72 h followed by blinded histopathology assessment. En bloc excision rates were: HK-ESD 100% versus CSI-EMR 20% (P = 0.008). The mean number of resections per lesion was HK-ESD 1 versus CSI-EMR 3 (P = 0.001). The mean dimensions of the largest specimen per technique were HK-ESD 63 × 54 mm versus CSI-EMR 49 × 41 mm (P = 0.005). Procedure duration mean was HK-ESD 54 min versus CSI-EMR 22 min (P < 0.001). When procedure duration was adjusted for the size of the resected en bloc specimen, a statistically significant and accelerated learning effect was noted for HK-ESD (r = -0.83, P = 0.003). There were no perforations and no significant bleeding. HK-ESD with SG submucosal injection is superior to CSI-EMR for en bloc excision of 50 mm diameter lesions in a porcine model. The technique is rapidly learnt. This novel approach may lower the barrier to colonic ESD for Western endoscopists.

A Randomized, Double-Blind Trial of Succinylated Gelatin Submucosal Injection for Endoscopic Resection of Large Sessile Polyps of the Colon

Succinylated gelatin (SG) is an inexpensive, safe, colloidal solution. It was superior to normal saline (NS) in a porcine colon endoscopic resection (ER) model. Our aim was to compare the efficacy, efficiency, and safety of ER with SG vs. NS. A randomized double-blind trial of submucosal injection with SG vs. NS was conducted for patients undergoing colonoscopy and ER for sessile lesions ≥20 mm in size at an Australian academic hospital endoscopy unit. The primary end point was the "Sydney Resection Quotient" (SRQ), defined as "lesion size in mm divided by the number of pieces to resect." This allows a comparison of technical outcomes for lesions of various sizes. A large lesion removed in fewer pieces gives a greater value. Eighty patients (45 men, mean age 69) with lesions sized 20-100 mm were randomized. A total of 41 SG subjects were well matched to 39 NS subjects, with median (interquartile range) lesion size 40 mm (25-45) vs. 35 mm (30-50), respectively (P=0.382). Complete single-session lesion excision was 90% in both groups. There were no adverse events attributable to SG. The SRQ (median (interquartile range)) was SG 10.0 (7.5-20.0) vs. NS 5.9 (4.4-11.7), P=0.004. Other end points (median (interquartile range)) included fewer resections per lesion in the SG group: 3.0 (1.0-6.0) vs. NS 5.5 (3.0-10.0), P=0.028; fewer injections per lesion with SG: 2.0 (1.0-3.0) vs. NS 3.0 (2.0-11.0), P=0.002; lower injection volume: 14.5 ml (8.5-23.0) vs. NS 20.0 ml (16.0-46.0), P=0.009; and shorter procedure duration with SG: 12.0 min (8.0-28.0) vs. NS 24.5 min (15.0-36.0), P=0.006. SG significantly improves SRQ by almost halving the number of resections for piecemeal ER. SG also safely halves procedure duration.

347l: Modification of Submucosal (SM) Injection Solution Significantly Improves Technical Outcomes in Colonic Endoscopic Mucosal Resection (EMR): A Randomized, Double-Blind Controlled Trial of Succinylated Gelatin (SG) Versus Normal Saline for EMR of Laterally Spreading Tumours (LSTs) and Large Sessile Lesions of the Colon

SG (Gelofusine®, B.Braun, Switzerland) is a clear, inexpensive, safe, colloidal plasma volume expanding solution that is commonly used for hypovolaemia. When compared to normal saline (NS) for SM injection in a porcine model, SG provided superior vertical elevation of the lesion resulting in a 42% increase in EMR specimen size. The present study is the first to investigate SG for human colonic EMR.

S1528: A Hybrid Circumferential Submucosal Incision Endoscopic Mucosal Resection (CSI-EMR) Technique Substantially Enhances En Bloc Resection Rates for 40 mm Artificial Lesions in a Porcine Colon Model

En bloc resection is preferred for laterally spreading tumours of the colon, but is limited to 20 mm with EMR using normal saline (NS) submucosal (SM) injection. We have shown that succinylated gelatin (Gelofusine®, B.Braun, Switzerland), a commonly available plasma volume expander, increases resection size by 42% when compared to NS in blinded porcine experiments. Therefore, our aims were to compare efficacy and safety of CSI-EMR versus conventional EMR for en bloc resection of 40x40mm lesions using succinylated gelatin (SG) SM injection.

Succinylated gelatin substantially increases en bloc resection size in colonic EMR: a randomized, blinded trial in a porcine model

Succinylated gelatin (SG) is an inexpensive colloid that may combine ease of use with the advantages of a colloid to potentially increase EMR specimen size, leading to a higher rate of en bloc resection. To evaluate the safety, efficacy, and impact on EMR specimen size of SG as a submucosal (s.m.) injectant in comparison with normal saline solution (NS). Randomized, blinded, controlled trial conducted with Animal Ethics Committee approval. Academic hospital. Ten swine. Sixty EMRs (30 using SG vs 30 using NS as 3 paired experiments per animal) of the largest possible en bloc snare resection of normal colonic mucosa after s.m. injection of a fixed volume of either SG or NS. EMR specimen size, duration of s.m. cushion, duration of procedure, ratio of vertical elevation to lateral spread of injectant, ease of resection, adverse effects, perforation, histopathology of EMR sites in colectomy specimens at necropsy (for inflammatory cell content, depth of ulceration, and vascular or ischemic changes). The mean subject weight was 53 kg. The mean EMR specimen dimensions and surface area were significantly larger with SG (length 37 vs 31 mm, P = .031; width 32 vs 26 mm, P = .022; surface area 9.5 cm(2) vs 6.7 cm(2), P = .044, respectively). The median s.m. cushion duration was 60 minutes with SG versus 15 minutes with NS (P = .005). The median procedure duration with SG was 2.6 minutes vs 2.5 minutes with NS (P = .515). The ratio of vertical elevation to lateral spread of injectant (mean score on a 3-point scale) was 3 with SG versus 2 with NS (P = .228). Ease of resection score (mean score on a 10-point scale) was 8 with SG versus 7 with NS (P = .216). There were no systemic adverse effects, hypersensitivity reactions, or bleeding episodes. There were 2 perforations (treated with clips) with SG and 1 with NS (P = 1.0). Blinded histopathologist assessment of necropsy colectomy specimens did not identify any significant differences between SG and NS EMR sites. Animal study. SG is safe and results in a 42% increased surface area for en bloc EMR. Given its other favorable properties, it represents a significant step toward defining the ideal EMR solution.

Progress Towards the Ideal Submucosal Injection Solution for Endoscopic Mucosal Resection (EMR) - A Randomized Blinded Trial of Succinylated Gelatin (SG) Versus Normal Saline (NS) for Colonic EMR in a Porcine Model

Progress Towards the Ideal Submucosal Injection Solution for Endoscopic Mucosal Resection (EMR) - A Randomized Blinded Trial of Succinylated Gelatin (SG) Versus Normal Saline (NS) for Colonic EMR in a Porcine Model

Controlled release of lysozyme from succinylated gelatin microspheres

Gelatin was anionized to increase the carboxylic acid groups through succinylation. Succinylation of gelatin was performed using varying amounts of succinic anhydride. This gave various percentages of substitution. Lysozyme, a cationic antibacterial enzyme, which has important applications in the reduction of prosthetic valve endocarditis, was chosen as a model protein drug. Microspheres were prepared using unmodified gelatin and succinylated gelatin (SG) and lysozyme was incorporated into them. The percentage loading and release profiles of lysozyme for gelatin and SG microspheres were evaluated and compared. It was found that the SG microspheres exhibited higher loading efficiency for lysozyme (50%) than the unmodified gelatin microspheres. The in vitro release of lysozyme from SG microspheres occurred up to 122 h, compared to 96 h for gelatin microspheres, for the release of most of the lysozyme incorporated. This prolonged release of lysozyme from SG microspheres was attributed to the electrostatic interaction between the cationic lysozyme and the anionic SG microsphere carrier.

Oxygen transport by a modified haemoglobin solution (PPSFH) in a dog model of acute anaemia following hypovolaemia

Polymerised pyridoxylated stroma free haemoglobin (PPSFH) is a potential red cell substitute. We compared PPSFH to Succinylated Gelatin (SG) and autologous fresh blood (AFB) in a dog model. Three groups of dogs were subjected to a period of fluctuating hypovolaemia. Eight received AFB and had a final haematocrit (Hct) of 54% and total active haemoglobin level (WBod Hb) of 16.5 g/dl. Eight received SG, had a final Hct of 20% and WBod Hb of 5.6 g/dl. Eight received PPSFH, had a final Hct of 20% and a WBod Hb of 10.4 g/dl. Those dogs receiving AFB responded to the hypovolaemic stress by raising oxygen consumption by 27%, whereas in both those receiving SG and PPSFH, oxygen consumption fell by 15% (p = 0.007). In the PPSFH group the PPSFH carried 43% of oxygen consumed. Thus, although PPSFH provided a higher circulating haemoglobin level than SG and carried a high proportion of oxygen consumed, it did not confer any advantage in terms of bulk oxygen transport.