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Aim: As reported previously, porcine skin gelatin exerted direct anti-tumor effect in vitro and induced anti-tumor peritoneal macrophages in vitro. The present study investigated whether or not the gelatin exerted anti-tumor effect in vivo., Methods: In vitro anti-tumor activities of peritoneal macrophages and the gelatin were evaluated with tritium thymidine uptake by target tumor cells. In vivo anti-tumor activity was evaluated with the survival of tumor-bearing animals and the size of the tumor., Results: Intraperitoneal daily administration of 12.5 mg of the gelatin prolonged the survival of mice which had been intraperitoneally inoculated with MH134 (hepatic cell carcinoma cell line) or Colon 26 (colon carcinoma cell line) tumor cells, and there were no tumors in case of MH134 cells inoculation. Intraperitoneal daily administration of 12.5 mg of the gelatin did not affect growth of subcutaneous MH134 tumor. The gelatin administered subcutaneously did not affect the survival of mice with intraperitoneal MH134 tumor. On the other hand, bovine skin gelatin administered subcutaneously achieved statistically significant prolongation of the survival. The contact of MH134 cells with porcine skin gelatin for 5 min was required for the gelatin to exert its anti-tumor activity in vitro. Porcine skin gelatin of 12.5 mg injected intraperitoneally was detected as protein in the peritoneal cavity 5 min after the injection. Peritoneal macrophages elicited by intraperitoneal injection with porcine skin gelatin suppressed tritium thymidine uptake by MH134 cells more strongly than those elicited by thioglycollate injection., Conclusion: Porcine skin gelatin administered intraperitoneally prolonged the survival of tumor-bearing mice via activation of peritoneal macrophages and involvement of direct anti-tumor activity of porcine skin gelatin. Key Words: porcine skin, gelatin, dissemination.

Objectives: This systematic review aims to assess the risks (both thromboembolic and bleeding) of an oral anticoagulation therapy (OAT) patient undergoing implant therapy and to provide a management protocol to patients under OAT undergoing implant therapy., Material and Methods: Medline, Cochrane Data Base of Systematic Reviews, the Cochrane Central Register of Controlled Trials and EMBASE (from 1980 to December 2008) were searched for English-language articles published between 1966 and 2008. This search was completed by a hand research accessing the references cited in all identified publications., Results: Nineteen studies were identified reporting outcomes after oral surgery procedures (mostly dental extractions in patients on OAT following different management protocols and haemostatic therapies). Five studies were randomized-controlled trials (RCTs), 11 were controlled clinical trials (CCTs) and three were prospective case series. The OAT management strategies as well as the protocols during and after surgery were different. This heterogeneity prevented any possible data aggregation and synthesis. The results from these studies are very homogeneous, reporting minor bleeding in very few patients, without a significant difference between the OAT patients who continue with the vitamin K antagonists vs. the patients who stopped this medication before surgery. These post-operative bleeding events were controlled only with local haemostatic measures: tranexamic acid mouthwashes, gelatine sponges and cellulose gauzes's application were effective. Post-operative bleeding did not correlate with the international normalised ratio (INR) status. In none of the studies was a thromboembolic event reported., Conclusions: OAT patients (INR 2-4) who do not discontinue the AC medication do not have a significantly higher risk of post-operative bleeding than non-OAT patients and they also do not have a higher risk of post-operative bleeding than OAT patients who discontinue the medication. In patients with OAT (INR 2-4) without discontinuation, topical haemostatic agents were effective in preventing post-operative bleeding. OAT discontinuation is not recommended for minor oral surgery, such as single tooth extraction or implant placement, provided that this does not involve autogenous bone grafts, extensive flaps or osteotomy preparations extending outside the bony envelope. Evidence does not support that dental implant placement in patients on OAT is contraindicated.

Background and Aims: The present study was carried out to test the hypothesis that interferon-alpha (IFN-alpha) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC)., Methods: 216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-alpha1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks., Results: The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4-25.8) and 20.3 months (95% CI: 15.8-24.8) in the TACE group (P = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P = 0.004). The median overall survival was 29 months (95% CI: 27.5-32.1) in the TACE-IFN group and 26 months (95% CI: 20.1-31.9) in the TACE group (P = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P = 0.003)., Conclusions: IFN-alpha treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.

Catalase delivery can be effective in inhibiting reactive oxygen species (ROS)-mediated acceleration of tumor metastasis. Our previous studies have demonstrated that increasing the plasma half-life of catalase by pegylation (PEG-catalase) significantly increases its potency of inhibiting experimental pulmonary metastasis in mice. In the present study, a biodegradable gelatin hydrogel formulation was used to further increase the circulation time of PEG-catalase. Implantation of (111)In-PEG-catalase/hydrogel into subcutaneous tissues maintained the radioactivity in plasma for more than 14 days. Then, the effect of the PEG-catalase/hydrogel on spontaneous pulmonary metastasis of tumor cells was evaluated in mice with subcutaneous tumor of B16-BL6/Luc cells, a murine melanoma cell line stably expressing luciferase. Measuring luciferase activity in the lung revealed that the PEG-catalase/hydrogel significantly (P<0.05) inhibited the pulmonary metastasis compared with PEG-catalase solution. These findings indicate that sustaining catalase activity in the blood circulation achieved by the use of pegylation and gelatin hydrogel can reduce the incidence of tumor cell metastasis.

A phenolic hydroxyl group was incorporated into gelatin, using aqueous-phase carbodiimide activation chemistry, to obtain in situ gellable and injectable protein-based materials for drug delivery and tissue engineering applications. By this means, gelatin derivatives that were gellable via a peroxidase-catalyzed reaction were obtained. The enzymatically cross-linked gelatin gels did not melt at 37 degrees C and showed tunable proteolytic degradability. The time necessary for gelation decreased with increasing content of the phenolic hydroxyl (Ph) group, peroxidase concentration and decreasing H(2)O(2) concentration. Resistance to gel compression also depended on the content of Ph groups, with the gel containing the lowest Ph group content showing the greatest resistance to compression. We encapsulated L929 fibroblast cells in gelatin gels under conditions that induced gelation in about 10 s. The encapsulated cells showed about 95% viability. In addition, L929 cells seeded on the gels showed the same growth profiles as those seeded on an unmodified gelatin-coated dish. Subcutaneous rodent injection experiments demonstrated successful in situ formation of gels at the injected site.

Current guidelines on initial haemodynamic stabilization in shock states suggest infusion of either natural or artificial colloids or crystalloids. However, as the volume of distribution is much larger for crystalloids than for colloids, resuscitation with crystalloids alone requires more fluid and results in more oedema, and may thus be inferior to combination therapy with colloids. This chapter describes the currently available synthetic colloid solutions [i.e., dextran, gelatin and hydroxyethyl starch (HES)] in detail, and critically discusses their specific effects including potential adverse effects. Literature was selected from medical databases (including Medline and the Cochrane library), as well as references extracted from the available publications. Dextrans appear to have the most unfavourable risk/benefit ratio among the currently available synthetic colloids due to their relevant anaphylactoid potential, risk of renal failure and, particularly, their major impact on haemostasis. The effects of gelatin on kidney function are currently unclear, but potential disadvantages of gelatin include a high anaphylactoid potential and a limited volume effect compared with dextrans and HESs. Modern HES preparations have the lowest risk of anaphylactic reactions among the synthetic colloids. Older HES preparations (hetastarch, hexastarch and pentastarch) have repeatedly been reported to impair renal function and hemostasis, especially when the dose limit provided by the manufacturer is exceeded, but no such effects have been reported to date for modern tetrastarches compared with gelatin and albumin. However, no large-scale clinical studies have investigated the impact of tetrastarches on the incidence of renal failure in critically ill patients. When considering the efficacy and risk/benefit profile of synthetic colloids, modern tetrastarches appear to be most suitable for intensive care medicine, given their high volume effect, low anaphylactic potential and predictable pharmacokinetics. However, the impact of tetrastarch solutions on mortality and renal function in septic patients has not been fully determined, and further comparison with crystalloids in prospective, randomized studies is required. Such studies are currently ongoing and their results should be awaited before drawing final conclusions on the HES preparations.

Proteins are the most satiating macronutrients. Tryptophan (TRP) may contribute to the satiating effect, as it serves as a precursor for the anorexigenic neurotransmitter serotonin. To address the role of TRP in the satiating properties of dietary protein, we compared three different breakfasts, containing either alpha-lactalbumin (high in TRP), gelatin (low in TRP) or gelatin with added TRP (gelatin+TRP, high in TRP), on appetite. Twenty-four subjects (22-29 kg/m2; aged 19-37 years) received a subject-specific breakfast at t = 0 with 10, 55 and 35 % energy from protein, carbohydrate and fat respectively in a randomised, single-blind design. Hunger, glucagon-like peptide (GLP)-1, ghrelin, amino acid concentrations and energy intake during a subsequent lunch were determined. Suppression of hunger was stronger 240 min after the breakfast with alpha-lactalbumin compared with gelatin and gelatin+TRP. Total plasma amino acid concentrations were lower with alpha-lactalbumin compared with gelatin with or without TRP (from t = 180-240 min). TRP concentrations were higher after alpha-lactalbumin than after gelatin with or without TRP from t = 0-100 min, whereas from t = 100-240 min, TRP concentrations were lower after gelatin than after alpha-lactalbumin and gelatin+TRP. The plasma ratio of TRP to other large neutral amino acids (LNAA) was, only at t = 100 min, lower after gelatin+TRP than after the other breakfasts. Plasma amino acid responses, TRP concentrations and TRP:LNAA ratios were not correlated with hunger. GLP-1 and ghrelin concentrations were similar for all diets. Energy intake during a subsequent lunch was similar for all diets. Summarised, an alpha-lactalbumin breakfast suppresses hunger more than a gelatin or gelatin+TRP breakfast. This cannot be explained by (possible) differences found in TRP concentrations and TRP:LNAA ratios in the breakfasts and in plasma, as well as in circulating total amino acids, GLP-1 and ghrelin.

Aim: Localized delivery of growth factors has significant potential as a future therapeutic strategy in tissue engineering and regenerative medicine. A nanoparticle vehicle was created and evaluated in this study with the intent to deliver growth factors for periodontal regeneration., Methods: Novel composite nanoparticles based on glycidyl methacrylate derivatized dextrans (Dex-GMA) and gelatin were fabricated by a facile method without using any organic solvents. The configurations of the resultant nanoparticles were evaluated by transmission electron microscopy, scanning electron microscopy, and atomic force microscope. Their surfaces were characterized by zeta-potential measurements, after which their properties including swelling, degradation, drug release, and cytotoxicity were also investigated using in vitro models., Results: The particle size of Dex-GMA/gelatin nanoparticles (DG-NPs) ranged from 20 to 100 nm and showed a mono-disperse size distribution (mean diameter 53.7 nm) and a strongly negative surface zeta potential (-20 mV). The DG-NPs were characterized by good swelling and degradation properties in media including dextranase. The in vitro drug release studies showed that the efficient bone morphogenetic protein (BMP) release from DG-NPs was maintained for more than 12 d under degradation conditions, where more than 90% of the loaded BMP was released. No any relevant cell damage caused by DG-NPs was found in the cytotoxicity tests for a period of 24 h., Conclusion: These combined results demonstrate that DG-NPs fulfill the basic prerequisites for growth factor delivery. With further in vivo studies, those nanoparticles may offer a promising vehicle for the delivery of active drugs to the periodontium.

Background & Aims: Dietary protein plays a role in body weight regulation, partly due to its effects on satiety. The objective was to compare the effects of casein-, soy-, whey-, whey without glycomacropeptide (GMP)-, alpha-lactalbumin-, gelatin-, or gelatin with tryptophan (TRP)-protein breakfasts at two concentrations on subsequent satiety and energy intake (EI)., Methods: Twenty-four healthy subjects (mean+/-SEM BMI: 24.8+/-0.5 kg/m(2); age: 25+/-2 years) received a breakfast; a custard with casein, soy, whey, whey-GMP, alpha-lactalbumin, gelatin, or gelatin+TRP as protein source with either 10/55/35 (normal) or 25/55/20 (high) En% protein/carbohydrate/fat in a randomized, single-blind design. At the precedingly determined time point for lunch, 180 min, subjects were offered an ad lib lunch. Appetite profile (Visual Analogue Scales, VAS) and EI were determined., Results: Both at the level of 10 and 25 En% from protein, EI at lunch was approximately 20% lower after an alpha-lactalbumin or gelatin (+TRP) breakfast (2.5+/-0.2 MJ) compared with after a casein, soy, or whey-GMP breakfast (3.2+/-0.3 MJ, p<0.05). Appetite ratings at 180 min differed 15-25 mm (approximately 40%, p<0.05) between types of protein. Differences in EI were a function of differences in appetite ratings (R(2)=0.4, p<0.001)., Conclusions: Different proteins (alpha-lactalbumin, gelatin, gelatin+TRP) that are approximately 40% more satiating than other proteins (casein, soy, whey, whey-GMP) induce a related approximately 20% reduction of subsequent energy intake.

Objective: To compare the long-term evolution of uterine arteries after embolization with the two most commonly used embolic agents for fibroid embolization: nonspherical polyvinyl alcohol (PVA) particles and trisacryl gelatin microspheres (TGMS)., Design: Prospective study., Setting: University-based interventional radiology, pathology, and reproductive physiology units., Animal(s): Two groups of 10 sheep embolized in the uterine artery., Intervention(s): Embolization of the uterine artery with either 600-1000 microm nonspherical polyvinyl alcohol (PVA) particles or with 700-900 microm trisacryl gelatin microspheres (TGMS). Animals were synchronized and naturally inseminated. Animals were killed at 26 months., Main Outcome Measure(s): Uteri were examined pathologically for vessel size, site of occlusion, recanalization rate of vessels, and particle location within the vascular wall., Result(s): The PVA particles were more numerous in the vessels' lumen than the TGMS particles (13.3 +/- 20.8 vs. 2.5 +/- 2.7), were located more proximally than TGMS (97% vs. 68% in the trunk and first branches of the uterine artery), and were found almost exclusively in the intima (99.2%). In contrast, 54.4% of the TGMS particles were found in the intima, and 45.6% partially or totally excluded. The rate of recanalization was not statistically significantly different for PVA and TGMS (65.2% vs. 60.6%)., Conclusion(s): The long-term evolution of uterine arteries was different after uterine artery embolization with PVA and TGMS because PVA particles formed large-sized aggregates that occluded proximal vessels and remained in the vessel intima. Microspheres occluded more distal vessels, and about 50% of them were partially or totally excluded from the vessel.

1. A precision feeding experiment was conducted to evaluate the effects of tannic acid (TA) and polyethylene glycol (PEG) on the excretion of amino acids, and the apparent and true digestibility of gelatin protein in broilers. 2. In a 3 x 2 x 2 factorial design, ninety-six 7-week-old broiler cockerels in 8 replicates of 12 treatments, were fed on warm solution of gelatin alone (0, 6 or 12 g/50 ml/bird, Treatments 1-3), or gelatin with TA solution (4.5 g TA/10 ml/bird, Treatments 4-6) and PEG solution (2 g/10 ml/bird, Treatments 7-12). Total excreta were collected for 48 h and the amino acid contents of gelatin and excreta were determined. 3. In the absence of TA, the digestibility of gelatin was almost complete. TA increased the excretion of amino acids from gelatin-fed birds to varying extents. Although the digestibility of all indispensable and dispensable amino acids was adversely affected by the presence of TA, increasing the amount of gelatin from 6 to 12 g improved the apparent and true digestibility of amino acids. PEG reduced the excretion of amino acids and improved the digestibility of amino acids in gelatin in TA-dosed birds. However, the effect was greater when the lesser amount of gelatin was fed. 4. In conclusion, PEG seemed to play an important role in reducing the effect of dietary tannins in the gastrointestinal tract of birds fed on diets high in tannins and improved protein digestibility and utilisation, particularly when the diet was low or marginal in protein.

The ratio of gelatin to sodium carboxymethyl cellulose (SCMC) at which maximum yield was obtained was optimized. This optimized ratio of gelatin to SCMC along with other parameters was used to prepare microparticles of different sizes. Vegetable oil was used as emulsion medium. Effect of various factors like amount of surfactant, concentration of polymer on the formation, and size of the microparticles was investigated. These microparticles were used as carrier for isoniazid. Among different cross-linkers, glutaraldehyde was found to be the most effective cross-linker at the temperature and pH at which the reaction was carried out. The loading efficiency and release behavior of loaded microparticles were found to be dependent on the amount of cross-linker used, concentration of drug, and time of immersion. Maximum drug loading efficiency was observed at higher immersion time. The release rate of isoniazid was more at higher pH compared to that of at lower pH. The sizes of the microparticles were investigated by scanning electron microscope. In all the cases, the microparticles formed were found spherical in shape except to those at low stirring speed where they were agglomerated. Fourier transform infrared study indicated the successful incorporation of isoniazid into the microparticles. Differential scanning calorimetry study showed a molecular level dispersion of isoniazid in the microparticles. X-ray diffraction study revealed the development of some crystallinity due to the encapsulation of isoniazid.

Polysaccharide-based colonic drug delivery requires that the polysaccharide in question avoids pancreatic digestion but undergoes fermentation by the colonic bacteria. Resistance of such dosage forms to pancreatic enzyme digestion is generally only tested in the fasted state, despite the higher enzymatic challenge in the fed state. Theophylline pellets coated with a polysaccharide-based (amylose) colon-specific film were administered to seven healthy volunteers (two-way crossover study, fed/fasted). The transit of the pellets through the gut was followed by gamma scintigraphy. The amount of drug released in the gut from the theophylline pellets was calculated after recovering and assaying any intact pellets in the faecal material. Of the drug released, the amount absorbed was measured using plasma profiling. Gastric empyting of pellets was delayed in the fed state, and this translated to a delayed colon arrival time. In both fed and fasted states, there was no drug release in the stomach or small intestine confirming the ability of the amylose in the coating to resist pancreatic digestion despite elevated enzyme levels in the fed state. Drug plasma levels were detected after the pellets arrived in the colon and there was a delayed T(max) in the fed state; the mean caecal arrival time in the fasted state was 5.5 +/- 1.1 h and the T(max) was 9.3 +/- 0.5 h, whereas in the fed state the mean caecal arrival time was 6.9 +/- 2.1 h and the T(max) was 10.3 +/- 0.8 h. On average, over 92% of the drug was released in the colon; the remaining was removed in faecal material. Bioavailability was similar (p>0.05) in both feeding states (26.0 +/- 6.4 microg h/ml fasted and 24.4 +/- 5.1 microg h/ml fed). In conclusion, feeding has no detrimental effects on the behaviour of this polysaccharide-based colonic delivery concept.

Hepatocyte growth factor (HGF) has an important role in many biological events such as angiogenesis and cell proliferation, as well as anti-fibrotic and anti-apoptotic effects. In addition, we found that HGF suppresses antigen-induced immune responses in the airway by suppressing dendritic cell functions, using a HGF-producing plasmid vector. In the present study, we examined whether delivery of the HGF protein in the lung attenuates allergic airway inflammation in a mouse model. Generally, HGF is rapidly cleared from organs. So, to achieve the efficient delivery of HGF, we prepared a slow-releasing form by mounting recombinant human (rh) HGF protein in biodegradable gelatin hydrogels. BALB/c mice were immunized and then challenged with ovalbumin (OVA) to induce eosinophilic airway inflammation. Intratracheal delivery of a very small amount of gelatin-coupled rhHGF (0.3 microg) just once before the inhalation of OVA significantly suppressed eosinophilic airway inflammation. In addition, cytokine production in thoracic lymph nodes and the antigen-presenting capacity of lung CD11c+ cells were reduced. In contrast, delivery of 1.0 microg of rhHGF did not exhibit any significantly suppressive effect. These results suggest that the controlled release of rhHGF protein can suppress antigen-induced allergic immune responses in the lung. Therefore, HGF could be a novel therapeutic option for asthma., (Copyright 2009 S. Karger AG, Basel.)

Besides crystalloids, colloids are used for the treatment of hypovolemia and shock. They are high-molecular-weight proteins of bovine origin with properties of more rapid replacement of circulating blood volume. Iso-oncotic character provides the volume effect (approximately equal to 100%) close to the volume intravenously infused with the duration of action for 2-4 hours. Gelatin solutions are excreted with urine and feces in unchanged form without prolonged fixation in organism. Even in case of acute renal failure, gelatin peptides do not accumulate due to increased activity of proteolytic enzymes; therefore, they are the first-choice colloids. Gelatin solutions do not change coagulation as other colloids; just they may cause hemodilution as crystalloids do, so they are safe in case of hemorrhage and thrombocytopenia. There is a decreased risk of bleeding when gelatin solutions are used in surgery as compared with other colloids; in addition, they protect from hypotension due to vasodilatation in epidural or spinal analgesia. Gelatin solutions may cause compensatory hyperemia and increase of cardiac output, cardiac index, myocardial contractility, mean arterial blood pressure, and diuresis; in addition, oxygen delivery to the tissues improves. The dosage depends on clinical condition of a patient, and it is suggested to be 100-2000 mL and even more, for isovolemic hemodilution--20 mL/kg of body weight. Adverse reactions such as anaphylactoid or anaphylactic to gelatin derivates are rare and similar to other colloids.

Poly(lactide-co-glycotide) (PLGA) microspheres integrated into gelatin/chitosan/hyaluronan scaffolds were fabricated by freeze-drying and crosslinking with 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide. The effects of the microspheres on porosity, density, compressive modulus, phosphate-buffered saline uptake ratio and weight loss of the scaffolds were evaluated. Generally, a scaffold with a higher PLGA content had a lower porosity and weight loss, and a medium uptake ratio, but a larger apparent density and compressive modulus. When the PLGA content was lower than 50%, the PLGA-integrated scaffolds had a similar pore size (approximately 200microm) as that of the control, and as much as 90% of their porosity could be preserved. In vitro chondrocyte culture in the 50% PLGA-integrated scaffold demonstrated that the cells could proliferate and secrete extracellular matrix at the same level as in the control gelatin/chitosan/hyaluronan scaffold.

Purpose: To determine the optimum combination strategy of transcatheter arterial chemoembolization and radiofrequency (RF) ablation in an experimentally induced hepatic tumor model., Materials and Methods: Twenty-five New Zealand White rabbits with VX2 carcinoma-induced hepatic tumors were randomly divided into five treatment groups, which received (i) chemoembolization followed 15 minutes later by RF ablation; (ii) RF ablation followed by chemoembolization; (iii) chemoembolization alone; (iv) RF ablation alone; and (v) bland embolization followed by RF ablation. Animals were euthanized at 48 hours to determine tumor infarction and coagulation, which were compared with analysis of variance. Representative histopathologic slides were compared., Results: Significantly larger areas of coagulation were produced by chemoembolization followed by RF ablation (22.0 cm(3) +/- 7.7) compared with RF ablation followed by chemoembolization (13.1 cm(3) +/- 3.2) and RF ablation alone (10.0 cm(3) +/- 4.5; P < .05). RF ablation followed by chemoembolization showed larger treatment areas than chemoembolization alone (25.0 cm(3) +/- 9.6 vs 12.1 cm(3) +/- 4.6; P < .001), with chemotherapeutic agent preferentially depositing around the coagulation zone. Histopathologic analysis revealed greater vascular thrombosis and necrosis and reduced islands of viable tumor cells in the chemoembolization/RF ablation group versus the groups treated with chemoembolization alone or bland embolization/RF ablation., Conclusions: Larger treatment volumes were produced when chemoembolization was performed before RF ablation than when RF ablation preceded chemoembolization or when RF ablation or chemoembolization were performed alone. Larger treatment volumes were also produced when chemoembolization rather than bland embolization was performed before RF ablation, indicating the importance and synergy of the chemotherapeutic regimen. These results suggest that the reduction of tumor blood flow combined with the effect of hyperthermia and local chemotherapy creates the largest dimensions of treatment.

In order to study the influence of different gelatin concentrations, and lymphocyte isolation liquid on primary culture of umbilical cord blood-derived adhesive cells (hCBACs), the red blood cells of umbilical cord blood was separated by 3% and 6 % gelatin for detecting the effectiveness of sedimentation, then the adhesion rate at 48 hours, the day of initial expansion and the rate of culture success were detected for hCBACs cultured with CD34(+) cells after the mononuclear cells were separated by 6% gelatin followed by Ficoll and Percoll, and the morphological characteristics and growth status were observed by invert microscopy. Cytochemistry stain for nonspecific esterase stain (NSE), peroxidase (POX), periodic acid Schiff reaction (PAS) and alkali phosphatase (ALP) and immunocytochemistry labeling for CD31, CD45, CD68 and fibronectin (Fn) were detected. The results showed that 6 % gelatin was better than that 3% gelatin for red blood sedimentation. The Percoll was predominant over Ficoll in adhesion rate at 48 hours, the day of initial expansion, the time of initial formation of adhesive cell colony units, the time of maximal numbers of adhesive cell colony units, the the cell fusion time and ratio of culture success. 60% fibroblast-liked cells, 36% macrophage liked cells and 4% small-round cells were observed in cells isolated by both isolated methods. The cytochemistry stain for NSE, POX, PAS and ALP was similar in two groups, the difference was not statistically significant between these two groups. The immunocytochemistry labeling for CD31, CD45, CD68 and Fn was also similar in both groups and the difference was also not statistically significant between these two groups. It is concluded that the combination of 6% gelatin with Percoll is an ideal separation method for primary culture of hCBACs, which provides basic information for clinical application.

Objectives: Pulmonary hypertension is a life-threatening disease, and alternative strategies are essential for patients with critical pulmonary hypertension. We developed a new procedure using microgelatin hydrogel microspheres incorporating basic fibroblast growth factor (mGHMs/bFGF) for intratracheal administration and evaluated the effect of a single intratracheal administration of mGHMs/bFGF on rats with monocrotaline-induced pulmonary hypertension., Methods: Monocrotaline was injected into 54 rats simultaneously with intratracheal administration of plain mGHMs (vehicle group), bFGF in solution form (free-bFGF group), mGHMs/bFGF (mGHMs/bFGF group), and plain saline with subcutaneous injection of saline instead of monocrotaline (control group, n = 18). Three weeks after the administration, 48 rats (n = 12 from each group) were subjected to hemodynamic and histologic evaluations. Survival was assessed in 6 rats of each group 10 weeks after the intratracheal administration., Results: The mGHMs/bFGF group showed significantly lower right ventricular/left ventricular pressure ratios at 3 weeks than the vehicle and free-bFGF groups (0.35 +/- 0.04, 0.54 +/- 0.11, 0.58 +/- 0.21, and 0.36 +/- 0.05 for the control, vehicle, free-bFGF, and mGHMs/bFGF groups, respectively; P < .01). Histologically, the mGHMs/bFGF group had a significantly higher number of vessels (diameter > or = 50 microm) than the other groups (5.3 +/- 2.6, 4.6 +/- 2.8, 7.3 +/- 2.5, and 18.9 +/- 7.0 vessels/mm(2), respectively; P < .01). Ten weeks after the intratracheal administration, 6 (100.0%) rats had survived in the control group, and 1 (16.7%) survived in the vehicle, 0 (0%) in the free-bFGF, and 5 (83.3%) in the mGHMs/bFGF groups (n = 6 each)., Conclusions: A single intratracheal administration of mGHMs/bFGF increased the number of vessels in the lung and ameliorated survival and hemodynamics in rats with monocrotaline-induced pulmonary hypertension.

Examination of 784 patients with acute intoxication with neurotropic agents yielded criteria for a risk of acute lung injury in this pathology and methods for diagnosing and treating this complication.

Background: A variety of local haemostatic agents is now available to stop troublesome bleeding. These agents are indicated for use during surgical interventions where conventional methods of haemostasis are not applicable because of the site of surgery or the degree of bleeding., Method: A literature search using the PubMed and ISI Web of Knowledge databases identified relevant studies on topical haemostatic agents. Manufacturers' recommendations were also sought through commercial websites., Results and Conclusion: A significant body of evidence now exists to support the use of topical haemostatic agents in a wide variety of clinical situations. The advantages and disadvantages of many of these agents are highlighted.

We describe a case of coronary artery perforation in a 76-year-old man, successfully treated by tris-acryl gelatin microsphere embolisation. This novel interventional embolic material is used in interventional radiology for arterial embolisation. We believe that this is the first report of its use for a coronary artery perforation.

The case report concerns about a 53 years old lady with Rendu-Osler-Weber disease, who was referred to our Department with the orbital apex syndrome after embolization of the internal carotid artery (ICA) due to repeating epistaxis. Immediately after the surgical procedure concerning the left-sided ICA, the patient complained about sharp hemicrania and pain of the ipsilateral eye, and diminished vision as well. The neurological and ophthalmologic examinations found decreased vision and limited movement of the eyeball on the left side. The patient was handed over to our Department inpatient care after one week after the surgery with clinically expressed syndrome of the left orbital apex--amaurosis, ptosis, total ophthalmoplegia, and protrusion of the eyeball. During the stay in the hospital, the progression of scotomas of the visual field with remaining concentric visual field on the right side (i.e. contralateral to the procedure) was found. The central vision of the right eye remained 20/20. The patient was treated by means of corticosteroids systemically as well as locally. The signs gradually subsided; during the control stay in hospital after three weeks after the surgery, the movements were limited in the far periphery only; slight ptosis and internal ophtalmoplegia remained; no protrusion of the eyeball was present; the amaurosis of the left eye remained permanent. In the visual field of the right eye, the concentric restriction disappeared and slight depression in the nasal half of the visual field remained only.

Study Design: Postero-lateral lumbar fusion in a rabbit model was performed to compare the bone induction potential of autograft, insoluble bone gelatin (ISBG), osteogenic protein-1 (OP-1), and the combination of ISBG and OP-1., Objective: To evaluate the efficiency of ISBG as a carrier/enhancer for OP-1 in a rabbit spinal fusion model., Summary of Background Data: OP-1 or recombinant human BMP-7 has been shown to be effective in inducing new bone formation in surgical applications such as spinal arthrodesis. However, the lack of an ideal carrier contributes to its associated comorbidities (e.g., uncontrolled bone growth, local inflammatory over-response, nonfusion) and limits its use clinically., Methods: Adult New Zealand white rabbits (n = 32) underwent bilateral lumbar intertransverse process fusion procedures at L5 to L6 and were randomized to receive: (1) autograft; (2) ISBG; (3) OP-1; or (4) ISBG in combination with OP-1 (ISBG + OP-1). Spinal fusion masses were evaluated by manual palpation, biomechanical testing, radiographic assessment, microcomputer tomography scanning and histologic examination at 6 weeks after surgery., Results: Treatment of ISBG + OP-1 resulted in higher spinal fusion rates (7 of 7, 100%) than that of autograft (3 of 7, 43%), ISBG (2 of 8, 25%), and OP-1 (2 of 7, 29%) based on manual palpation (P < 0.01). Greater fusion rates in the ISBG + OP-1 group were also evidenced by radiographic examination (P < 0.01), microcomputer tomography bone volume analysis (P < 0.01), and biomechanical testing (P < 0.05). Histologic assessment demonstrated that treatment of ISBG + OP-1 induces new contiguous bone formation in the interval between the transverse processes which was absent in the other groups., Conclusion: In this study, ISBG + OP-1 resulted in more effective lumbar intertransverse process fusion than autograft, OP-1 putty or ISBG alone. ISBG is capable of enhancing OP-1-induced bone formation.

Biosurgical compounds and pharmacologic agents can serve as surgical adjuncts to prevent or curtail intraoperative bleeding. Medline, PubMed, and Cochrane electronic data bases were used to search the English literature from 1966 to March 2007 using the terms topical, hemostatic agents, and gynecologic surgery. Several effective topical hemostatic agents are available to reduce intraoperative blood loss. Data on their application in gynecologic surgery are limited, and guidelines for selecting one over another for specific indications are lacking.

Injectable and thermo-reversible physical combination gels were formed in aqueous solution by preparing complex coacervate with two oppositely charged biomacromolecules that composed of negatively charged chondroitin 6-sulfate and positively charged high molecular weight gelatin type A and co-formulating with a negative, thermo-sensitive polysaccharide, methylcellulose containing a salting-out salt, ammonium sulfate. The combination of complex coacervation and a thermo-reversible gel demonstrated synergistic effects on the complex coacervate formation the release rates of model proteins and in situ gel depot formation. Gels indicated sustained release patterns of the protein over 25 days with minimal initial bursts. Optimized novel in situ gel depot systems containing dual advantages of complex coacervation and temperature responsiveness demonstrated a potential for efficient protein drug delivery in terms of high protein loading, sustained protein release, ease of administration, an aqueous environment without toxic organic solvents, and a simple fabrication method.

The purpose of this study was to evaluate the size responses and vascular responses to three different sizes of Embosphere (EMBS) embolization particles used for chemo-embolization in patients with unresectable hepatocellular carcinoma (HCC). Forty-seven patients with biopsy proven HCC treated with TACE using EMBS (Biosphere Medical, Rockland, MA, USA) were included in this study. EMBS are non-resorbable tris-acryl gelatin defined-size microspheres. Sixteen patients were treated with 40-120 micron (40-microm), 13 patients with 100-300 (100-microm), and 18 patients with 300-500 (300-microm) EMBS particles. We measured the two-dimensional area and vascularity of the tumor index lesion on initial and subsequent CTs after treatment. Lesions were classified into four grades based on the degree of vascularity measured in 25% increments. Size of tumor after one treatment decreased by an average (avg) of 18% for 40-120-microm particles, 38% for 100-300-microm particles, and 17% for 300-500-microm particles. After three treatments, size decreased by an avg of 46% for 40-120-microm particles, 76% for 100-300-microm particles, and 46% for 300-500-microm particles. Vascularity decrease was also measured after the first and third treatments, and defined as a decrease of one or more grades in tumor vascularity. Results were as follows (% of patients with decrease). For 40-120-microm particles: 1 and 3 treatments, 53% and 88% of patients. For 100-300-microm particles: 1 and 3 treatments, 60% and 88% of patients. For 300-500-microm particles: 1 and 3 treatments, 50% and 57% of patients. It was concluded the 100-300-microm EMBS particles produce slightly higher responses.

We compared the clinical efficacy of autologous platelet gel (APG) and gelatine (CONT), including biomaterial evaluation. In a prospective, randomized, controlled trial, 64 patients undergoing complex coronary artery bypass graft (CABG) surgery and/or aortic surgery, in whom the surgeon was able to identify a bleeding site for which conventional means to stop bleeding were impractical or proved unsuccessful, were enrolled. Aortic punch biopsy from each patient was harvested in explant cell (EC) culture media. Hemostasis success for the "oozing" category was 89% in APG and 60% in CONT (p< 0.05). For the "heavy bleeding" category, the success rates were 92% in APG and 45% in CONT (p<0.01). Contact of gelatine inhibited EC proliferation and APG increased cell cycling and EC quantity. Phagocytic capacity (PC) was significantly higher in the APG group (p<0.001). APG was significantly better than CONT with respect to hemostatic success rate, effects on wound healing and increased resistance to infection (PC).

Insulinomas are rare, mostly benign neuroendocrine tumors, originating in 99% of cases from the pancreas, that synthesize and secrete insulin, causing symptomatic hypoglycemia. Today the treatment of choice is surgical removal. We present the case of an 84-year-old woman with a symptomatic insulinoma who refused surgery and was treated with arterial embolization using trisacryl gelatin microspheres as definitive treatment.

Background: The effects of hydroxyethylstarch (HES) 130/0.4 6% and gelatin 4% on inflammation, endothelial integrity, and renal function after cardiac surgery were compared., Methods: Sixty patients aged >80 yr undergoing cardiac surgery were randomized to receive gelatin (n=30) or HES 130/0.4 (n=30). The colloid was used in the priming of the cardiopulmonary bypass circuit (500 ml) and for volume replacement until the second postoperative day (POD). Serum creatinine, creatinine clearance, IL-6, IL-10, intercellular adhesion molecule-1 (sICAM-1), urinary glutathione transferase-alpha, and neutrophil gelatinase-associated lipocalin (NGAL) were measured perioperatively. Serum creatinine was also reported approximately 60 days after discharge., Results: The mean(sd) volume of gelatin infused was 4180(440) ml, which was greater than the volume of HES infused 2910(330) ml (P=0.002). The mean(sd) volume of serum creatinine on the first POD was 151(24) micromol litre(-1) in the gelatin group and 126(13) micromol litre(-1) in the HES group (P=0.004). Values for the second POD were 161(0.26) and 133(16) micromol litre(-1), respectively (P=0.004). Creatinine clearance was lower in the gelatin group on the first POD [37(7) vs 46(8) ml min(-1) 1.73 m2 (P=0.004)] and the second POD [32(8) vs 45(10) ml min(-1) 1.73 m2 (P=0.002)]. Kidney function approximately 60 days after discharge did not differ between the groups. IL-6, IL-10, and sICAM-1 were significantly lower in the HES group than in the gelatin group on the first and second PODs. Urinary alpha-GST increased in both groups to a comparable extent. Urinary NGAL concentrations were higher in the gelatin than in the HES patients 5 h after surgery and on the first and second PODs., Conclusions: In cardiac surgery patients aged >80 years, volume therapy with HES 130/0.4 6% was associated with less marked changes in kidney function and a less marked endothelial inflammatory response than gelatin 4%.

Very elastic poly(L-lactide-co-epsilon-caprolactone) (PLCL) (50:50) copolymer blended with gelatin was electrospun into microfibers from a hexafluoroisopropanol solution. PLCL fiber sheet exhibited the unique soft and flexible behavior while gelatin fiber was hard and brittle. As the gelatin content of PLCL/gelatin fibers increased, Young's modulus was increased, but the elongation was decreased compared to those of PLCL. However, fibers containing 10-30 wt% gelatin demonstrated an enhanced tensile strength with still high elongation to be beneficial for tissue engineering scaffolds. The cytocompatibility of electrospun fiber sheets was evaluated by fibroblasts (NIH-3T3) cell culture. The initial cell adhesion on various fibers after 5h was somewhat similar, but in the order of PLCL>PLCL70/gelatin30 approximately PLCL50/gelatin50>PLCL90/gelatin10 approximately gelatin>PLCL30/gelatin70. However, the cell proliferation exhibited a completely different and strong dependence on the fiber composition: a very high proliferation rate on PLCL90/gelatin10, followed by PLCL>gelatin>PLCL70/gelatin30. Such an enhanced effect of gelatin, especially at 10 wt% content, on strength and cytocompatibility of PLCL/gelatin fibers would be very preferable for tissue engineering scaffolds.

Autoimmune alopecia (alopecia areata) is considered to be triggered by a collapse of immune privilege in hair follicles. Here we confirmed that infiltrating CD4 T lymphocytes around hair follicles of patients with alopecia areata were primarily CCR5-positive with few CCR4-positive cells, suggesting a dominant role of Th1 cells in the alopecic lesion. Given this finding, we sought to elucidate the effect of cytokine therapy in C3H/HeJ mice, a mouse model of alopecia areata, by applying recombinant interleukin-4 and neutralizing anti-interferon-gamma antibody. We found that local injections of both interleukin-4 and neutralizing anti-interferon-gamma antibody effectively treated alopecia in C3H/HeJ mice. Results from immunohistochemistry and semiquantitative reverse transcription-polymerase chain reaction demonstrated that intralesional injection of interleukin-4 suppressed CD8 T cell infiltrates around the hair follicles and repressed enhanced interferon-gamma mRNA expression in the affected alopecic skin. Furthermore, Th1 transcription factor T-box21 small interfering RNAs conjugated to cationized gelatin showed mitigating effects on alopecia in C3H/HeJ mice, resulting in the restoration of hair shaft elongation. Taken together, the use of gelatin-small interfering RNA conjugates promises to be a novel, efficient, and safe tool as an alternative gene therapy for the treatment of various human diseases. To our knowledge, this is the first report of effective controlled delivery of small interfering RNA using biodegradable cationized gelatin microspheres in an animal model of disease.

A well-timed delivery of bioactive macromolecules from the porous scaffolds is very important in tissue engineering. Tetrandrine (Ted) is one of a large number of known plant derived bisbenzylisoquinoline alkaloids and is obtained from the roots of Stephania tetrandria. Ted can be used as a modifier to poly(l-lactic acid) scaffolds to promote chondrocyte differentiation and secrete type II collagen. But the effect of Ted on chondrocyte's behavior strongly depends on the concentration of Ted in the culture media. Here amphiphilic diblock copolymer (PLAE) composed of l-lactide and methoxy poly(ethylene glycol) (MePEG) was prepared and the Ted loaded copolymeric nanospheres were obtained by self-emulsification and then solvent evaporation. The mean sizes of core/shell type PLAE nanospheres and Ted-loaded nanospheres are about 60 and 100nm, respectively. Chitosan-gelatin (Cs-Gel) porous scaffolds loaded with PLAE-Ted nanospheres were fabricated through freeze drying. Ted release behaviors from PLAE-Ted nanospheres and porous scaffolds were investigated. The result shows that the Ted-loaded nanospheres could be embedded within Cs-Gel scaffolds and no initial burst release could be observed in the release patterns. Here a room can be provided for the scaffolds to sustained release bioactive component in tissue engineering.

This study focused at the potential of transforming growth factor beta 1 (TGF-beta 1) loaded gelatin microparticles to enhance the bone response and mechanical strength of rabbit femoral defects filled with injectable calcium phosphate (CaP)/gelatin microparticle composites. Therefore, TGF-beta1 loaded composites and non-loaded controls were injected in circular defects as created in the femoral condyles of rabbits and were left in place for 4, 8 and 12 weeks. The specimens were evaluated mechanically (push-out test), and morphologically (scanning electron microscopy (SEM), histology, and histomorphometry). The results showed a gradual increase in mechanical strength with increasing implantation periods. Histological and histomorphometrical evaluation showed similar results for both composite formulations regarding histological aspect, new bone formation and bone/implant contact. However, TGF-beta1 loading of the composites demonstrated a significant effect on composite degradation after twelve weeks of implantation. The results of this study showed that CaP/gelatin composites show excellent osteogenic properties and a rapid increase in mechanical strength. The addition of TGF-beta1 significantly enhances the bone remodeling process.

Use of gelatin/resorcinol/formaldehyde glue as a tissue adhesive and hemostatic agent was evaluated experimentally after modification of the aldehyde component. Gelatin/ resorcinol/aldehyde (GRA) glue was prepared by mixing gelatin and resorcinol and cross-linking with a blend of formaldehyde/glutaraldehyde. After wedge resection of the liver of 28 albino rats, bleeding was controlled, and the cut surfaces were joined with GRA. Liver biopsy was done at 7, 14, 21, and 28-day intervals. Hemostasis was excellent in 71.4%, satisfactory in 25.0%, and poor in 3.6%. Mean time for tissue adhesion was 2.6 minutes. No necrosis or bile leakage was seen. Visibility of site of repair decreased from 50.0% on day 7 to 14.3% on day 28. Residual glue was seen microscopically on day 28 in 43% cases. GRA is safe and good hemostatic, tissue adhesive, and sealant in rat liver.

Selective modulation of sensory neuron gene expression could have numerous applications for the peripheral nervous system. Here, we report that subcutaneous peripheral injection of plasmid DNA complexed with a non-viral cationized gelatin (CG) vector led to transgene expression in rat lumbar dorsal root ganglia (DRGs). CG/DNA polyplexes appeared to undergo rapid retrograde transport through sciatic and spinal nerves, with reporter gene messenger RNA (mRNA) expression detectable in L4 and L5 DRGs within 60 hours. Maximum transgene expression was observed for polyplexes formed at 7.5:1 CG-to-DNA weight ratio under salt-free conditions, which generated 615 +/- 112 nm nanoparticles with zeta-potential of 9.4 +/- 0.19 mV. Six days after injection of the CG/DNA polypex, reporter gene protein immunofluorescence was observed in 1,164 +/- 176 DRG neurons, representing an estimated transfection rate of 47% of targeted neurons. Reporter gene expression was not detected in heart, lung, or liver tissues, suggesting a lack of systemic uptake. Measurements of tactile sensitivity indicate that CG/DNA injection did not cause behavioral toxicity. The injection platform was further used for plasmid-driven short hairpin RNA-mediated suppression of glyceraldehyde-3-phosphate dehydrogenase. This non-invasive gene delivery system could be used for the mechanistic study and targeted molecular evaluation of peripheral nervous system pathologies such as neuropathic pain.

Gelatin-stabilised microemulsion-based organogels (MBGs) are very useful in transdermal and topical delivery of hydrophobic drugs because of their lipophilic nature. MBGs systems possessing a potentially improved skin bioavailability of Cyclosporin A were designed and explored for some characteristics. The release characteristics of drug from MBGs were studied according to drug concentration. As the concentration of drug increased, the release of drug from gel increased, showing concentration dependency. Percutaneous penetration studies using rat skin in vitro showed that the deposition of Cyclosporin A was significantly improved by MBGs compared to the control. We also evaluated the therapeutic advantage of dermal administration of Cyclosporin A in rat model. Local (subcutaneous and skin), systemic concentrations and organ distribution (liver and kidney) were evaluated serially following topical and oral application of the drug. In rat dermal applied with the MBGs containing Cyclosporin A, the deposition of the drug into skin and subcutaneous fat was, respectively, almost 55- and 3-fold higher than the concentrations compared with oral administration. Systemic distribution in blood, liver and kidney was much lower following topical than following oral administration. With high local concentrations and minimal distribution to other organs via the circulation, topical applied MBGs loaded with Cyclosporin A might deliver maximal therapeutic effect to local tissue while avoiding the side effects seen with systemic therapy. The histopathological findings revealed that the new MBGs vehicle was a safe vehicle for topical drug delivery systems., (Copyright 2007 Wiley-Liss, Inc.)

Purpose: To assess by magnetic resonance (MR) imaging the detectability of superparamagnetic iron oxide (SPIO)-labeled microspheres (MSs) in vitro on gelose, ex vivo in kidneys from embolized sheep, and in vivo in kidneys from embolized pigs., Materials and Methods: With various sizes of SPIO-labeled MSs, common neck and pelvic spin-echo and gradient-echo sequences were acquired on a 1.5-T MR unit. SPIO-labeled MSs of four sizes were embedded in a hydrogel as single MSs or in multiple units, or multiplets. Detection rate on MR imaging was assessed according to the real size and number of MSs. SPIO-loaded and unloaded MSs of four sizes were injected into eight sheep kidneys, which underwent MR and pathologic examinations. For each size, the location of MSs in renal vasculature was determined and compared according to the technique used. Kidneys were embolized in pigs with various amounts of MSs in three sizes. MR was performed immediately after embolization and SPIO-labeled MS detection was assessed according to size, organ, and amount injected. Results SPIO-labeled MSs provide a low signal intensity on T1-weighted sequences, without distortion. In vitro, 28% of 100-300-microm single MSs were detected and more than 80% were detected for larger sizes. MS multiplets were all detected in all sizes. Ex vivo, all sizes of MSs were detected by MR imaging in kidneys, whereas control MSs were not observed. Histologic analysis showed that there was no difference in vascular distribution between SPIO-labeled MS and control MSs, and therefore for each caliber (P > .05). Arterial location of SPIO-labeled MSs was the same on MR imaging and histologic analysis. In vivo, SPIO-labeled MS were detected in the kidney vasculature when volumes greater than 1 mL of 100-300-microm or 500-700-microm MSs were injected. Volumes lower than 1 mL SPIO-labeled MSs were hardly detected in kidneys, regardless of MS size. Conclusions SPIO-labeled MSs are detected by MR imaging with common gradient-echo sequences in vitro in gelose and ex vivo and in vivo in kidneys. SPIO-labeled MSs could allow better control of embolization and thereby enhance efficacy and safety of the procedure.

Background: To explore whether disturbed fibrin polymerization is the main problem underlying dilutional coagulopathy and can be reversed by fibrinogen administration, we conducted a prospective study using modified thrombelastography (ROTEM)., Methods: Sixty-six orthopedic patients randomly received modified gelatin solution, hydroxyethyl starch 130/0.4, or exclusively Ringer lactate solution. ROTEM analysis was performed, concentrations of coagulation factors and markers of thrombin generation were measured. Fibrinogen concentrate (Hemocomplettan) was administered (30 mg/kg) when thrombelastographically measured fibrinogen polymerization was critically decreased., Results: The alpha angle, clot firmness, and fibrinogen polymerization (median [min to max]) significantly decreased in the patients receiving hydroxyethyl starch (area under the curve minus baseline (-5 [-9 to -2]), followed by gelatin solution (-3 [-8 to 0]), with the least reductions seen for Ringer lactate solution (-2 [- 4 to 1]) (colloids versus Ringer lactate P < 0.0001). Thirteen patients in the colloid groups but none in the Ringer lactate group needed fibrinogen concentrate to maintain borderline clot firmness. Activity of FVII, FVIII, FIX, and von Willebrand ristocetin activity decreased significantly with colloids. Thrombelastographically measured coagulation time, molecular markers of thrombin generation, and activity of all other coagulation factors were comparable in all groups., Conclusion: Disturbance of fibrinogen/fibrin polymerization is the primary problem triggering dilutional coagulopathy during major orthopedic surgery. The magnitude of clot firmness reduction is determined by the type of fluid used, with hydroxyethyl starch showing the most pronounced effects. These undesirable effects of intravascular volume therapy can be reversed by increasing fibrinogen concentration by administering fibrinogen concentrate, even during continuing blood loss and intravascular volume replacement.

Uterine artery embolization (UAE) for the treatment of symptomatic leiomyomata has shown excellent short-term clinical efficacy and minimal complications, yet recurrences after successful treatments at mid- and long-term follow-up have been reported. Exact etiologies for such recurrences have not been fully understood. We present a case of symptom recurrence with the development of a hypertrophic ovarian artery after successful UAE with polyvinyl alcohol particles, successfully treated with ovarian and repeat UAEs.

Background: As an extension of our previous studies on bioabsorbable pericardial substitutes, we have created a new form of gelatin sheets latticed with bioabsorbable polyglycolic acid (PGA). This study was undertaken to evaluate the biomechanical property of the sheet and the preventive effect on pericardial adhesions after pericardial replacement in a canine model before its clinical applications., Methods: The mechanical property was assessed by measuring tension of suture pull-out at first break test. Fifteen dogs underwent partial pericardial replacement with the bioabsorbable sheets through a left thoracotomy. Macroscopic assessment for severity of adhesions and microscopic evaluation for histologic changes were made at 2, 4, 12, and 24 weeks postoperatively., Results: The latticed sheets exhibited tenfold higher tension of disruption at the suturing margin compared to our previously developed gelatin sheets (619 +/- 141 versus 62 +/- 7 gf, p < 0.001), and demonstrated equivalent strength to that of clinically available expanded polytetrafluoroethylene membrane. During rethoracotomy, adhesions between the epicardium and the pericardial substitutes were moderate at the 4-week interval and resolved completely after 12 weeks postoperatively. Inflammatory reaction scores graded into 4 scales on histologic assessment were 2 +/- 0.0, 1.6 +/- 0.6, and 0.3 +/- 0.5 at 4, 12, and 24 weeks, respectively. Inflammatory reaction significantly decreased from the 4-week interval to the 24-week interval after the pericardial replacement (p < 0.05)., Conclusions: The bioabsorbable gelatin sheets latticed with PGA gained improved mechanical properties compared with the previously reported gelatin sheets without impairing its bioabsorbability. The bioabsorbable sheet could eliminate pericardial adhesions after being replaced with regenerated tissue.

A 60 days experiment was conducted to study the effect of dietary gelatinized (G) and non-gelatinized (NG) starch on immunomodulation of Labeo rohita juveniles. Two hundred and thirty four juveniles (av. wt. 2.53+/-0.04) were randomly distributed in six treatment groups with each of three replicates. Six semi-purified diets containing NG and G corn starch, each at six levels of inclusion (0, 20, 40, 60, 80, 100) were prepared viz., T(1) (100% NG, 0% G starch), T(2) (80% NG, 20% G starch), T(3) (60% NG, 40% G starch), T(4) (40% NG, 60% G starch), T(5) (20% NG, 80% G starch) and T(6) (0% NG, 100% G starch). After a feeding period of 60 days, the juveniles were challenged with Aeromonas hydrophila to study their immunomodulation due to feeding of G and NG starch. RBC and haemoglobin content were significantly (P<0.05) reduced due to bacterial challenge, but dietary starch (G/NG starch) had no effect on it. G:NG starch ratio in the feed had significant effect on total leukocyte count during pre- and post-challenge periods. The leukocyte count concomitantly increased with the increased level of G starch in the diet. Highest albumin/globulin (A/G) ratio was recorded in T6 group (100% G starch) and lowest in T1 group (100% NG starch) group followed by T2 group both in pre- and post-challenge periods. NBT, lysozyme activity, total protein and globulin content were highest in T2 group (80% NG, 20% G starch) both in pre- and post-challenge periods. After challenge with A. hydrophila, the highest survival was recorded in T2 group, whereas lowest survival was recorded in T6 group. Conclusively high level of G starch was found to be immunosuppressive in Labeo rohita juveniles and NG:G starch ratio of 80:20 seems to be optimum for promoting growth and protecting immunity in L. rohita juveniles.

The guinea-pig was previously reported as being sensitive to a niacin-deficient (ND), high-protein diet, suggesting that it is a suitable model for the low tryptophan to NAD+ conversion observed in human subjects. However, these studies were based on growth rates and mortality. The objective of the present study was to determine whether guinea-pigs are suitable for ND studies based on measurements of blood and bone marrow NAD+. Using a 20 % casein diet, ND decreased blood NAD+ after 4 weeks, but this parameter returned to normal after 9 weeks of feeding, while bone marrow was decreased by 35 % at this time point. Using a 15 % casein diet, 7 weeks of ND caused 44 and 42 % decreases in blood and bone marrow NAD+. Using a 10 % casein diet, ND decreased NAD+ by 32 % in blood and 62 % in bone marrow at 7 weeks. Growth rates were directly related to the dietary tryptophan content, with the lowest growth rates seen with the 10 % casein diet. Changes in guinea-pig NAD+ are comparable with the rat model at similar levels of dietary tryptophan, while mortality rates were dramatically higher in the guinea-pig model. The present study concludes that mortality in ND guinea-pigs is not indicative of poor tryptophan conversion, but is due to environmental stresses in guinea-pigs that are not observed with rats. We conclude that guinea-pigs are not suitable for research on niacin deficiency and they present challenges for any study requiring purified diets and wire-bottomed cages.