Gelatin Foam Research Articles

Melanocortins in peripheral nerve regeneration: Influence of dosage forms and routes of administration

Neutrophic peptides derived from the melanocortin (ACTH/MSH) family stimulate both in vitro and in vivo the outgrowth of neuntes from developing neurones or damaged nerves. In medical biology the search for a new lead in the pharmacotherapy of brain and nerve lesions is tremendous as the incidence of especially aged related neurodegenerative diseases and nervous system trauma in a greying society is profound and currently little, if any, specific drug treatment seems to be at hand. In rats, the efficacy of melanocortins in accelerating functional recovery from sciatic nerve damage following various types of sub-cutaneous and oral administration was assessed. Rats bearing a crush lesion in the sciatic nerve and receiving melanocortins as a subcutaneous bolus injection every other day showed an accelerated recovery of function as tested in a foot withdrawal test or a walking pattern analysis. Sustained release from osmotic ALZET-minipumps or from lactate/glycolate biodegradable microspheres, both dosage forms implanted subcutaneously, were similarly effective. Although melanocortins have been shown to affect some CNS function following oral administration, both delivery via drinking water and via a stomach tube rendered the peptide ineffective in facilitating peripheral nerve repair. In the study on the pharmacotherapy of nerve trauma, local application of neurotrophic factors is both feasible as well as implicated by pathophysiological mechanisms governing post-lesion neurite outgrowth. In experiments concerning the repair of transected nerves we used microporous Accurel ® polypropylene tubes to enclose the site of injury. The Accurel ® can adsorb high quantities of peptides and this feature was used to deliver α-MSH at the repair site of sutured rat sciatic nerve. In studies on the crushed nerve, local application of the peptide was achieved by wrapping apeptideimpregnated biodegradable gelatine foam matrix (Willospon ®) around the site of injury. Under both conditions local delivery leads to enhanced recovery of function following sciatic nerve damage. That local delivery and not leakage from the local site via systemic routes facilitated the recovery process was evident from control studies where the gelatine foam was wrapped around the contralateral nerve and no facilitated recovery could be established in the ipsilateral crushed nerve. Although currently there is little insight into the actual amount of peptide reaching the site of injury via the different routes of administration, it seems appropriate to conclude that a peak amount of peptide must be available in a short period following the nerve damage to faciliate the repair process. In the clinic different routes may be selected depending upon the nature of the nerve damage, i.e. mechanical trauma (local, biodegradable) or intoxication (bolus injection or biodegradable microspheres).

Dynamic aspects of airborne bacterial flora over an experimental area in a suburb and distribution of resistant strains to antibacterial agents among airborne staphylococci.

Airborne bacterial floras were investigated at stations A to E and P on the UOEH campus located in a suburb of the city of Kitakyushu. Bacterial collections were carried out by a filtration method using a soluble gelatin foam filter at an altitude of 1 m from the ground and viable bacterial cells were enumerated on nutrient agar plates supplemented with 50 micrograms/ml cycloheximide. At station P, where airborne bacterial composition was evaluated as a mean value of 20 repeated experiments, there were 42% Gram-positive cocci, 37% Gram-positive rods, 3.5% Bacillus strains and 5.5% Gram-negative rods. Fluctuating values of cell amounts for Gram-positive cocci and rods during these experiments suggested that in the atmospheric layer near the ground, the former was a more transient group of airborne bacteria than the latter. When airborne bacterial flora over the experimental area was surveyed by observations at six stations, the dispersion profile of bacterial flora closely corresponded to vegetating states on the surface of the ground. Over vegetating areas, airborne bacterial flora appeared in about equal amounts of Gram-positive rods and cocci, while over bare ground, Gram-positive rods appeared more abundantly than Gram-positive cocci. To investigate the distribution of drug-resistant strains among airborne bacteria, sensitivity tests to six antibiotics were carried out with S. xylosus strains isolated at stations P and E. As a result, considerable amounts of single-drug-resistant strains for TC (DOX) and EM were recognized, but the distribution of multiple-drug-resistant S. xylosus was restricted to a few strains.

Evaluation of temporary liver dearterialization and embolization in patients with metastatic carcinoid tumour.

Patients with serotonin-containing metastatic midgut carcinoid tumours were treated with temporary liver dearterialization (19 patients) or liver embolization (8 patients). After 3, 6 and 12 months the effects of treatment were registered in changes in serotonin in platelet-poor plasma and blood, in urinary 5-HIAA, in tumour extent in the liver and in symptomatic relief. Seventeen patients, who underwent the dearterialization procedure survived the operation, while 2 patients who had a concomitant small bowel resection died of complications. Tumour response was obtained in 8 patients after 6 months and in 9 patients after 12. Stable disease was noted in 5 patients after 6 months and 3 patients after 12 months. Progressive disease was seen in 4 patients. All 19 patients except one exhibited the carcinoid syndrome prior to operation and 11 patients were free from symptoms for at least 12 months postoperatively. The gelatine foam powder liver embolization was performed uneventfully in all 8 patients. Tumour response was obtained in 3 patients at both 3 and 12 months. Stable disease was noted in 5 patients at 3 months and 4 patients at 12 months. Before embolization the patients suffered from the carcinoid syndrome and the treatment resulted in the immediate disappearance of the syndrome in 5 patients. After 12 months one patient was still free from obvious carcinoid symptoms. In one patient the disease aggravated in spite of treatment and he died 5 months after embolization. Thus, temporary liver dearterialization and liver embolization in midgut carcinoid patients resulted in tumour regression and symptomatic relief in 9 out of 19 patients and 3 out of 8 patients respectively. The complication rate was low.

α-MSH and Org.2766 in peripheral nerve regeneration: different routes of delivery

The efficacy of melanocortins (α-MSH and an ACTH-(4–9) analog, Org. 2766) in accelerating functional recovery from sciatic nerve damage following various types of subcutaneous and oral administration was assessed in the rat. Furthermore, the effectiveness of the local delivery of melanocortins to the site of injury was examined. An accelerated recovery was evident following subcutaneous constant delivery of Org.2766 from an osmotic mini-pump and from biodegradable polymere microspheres, and was as effective as repeated subcutaneous injections of α-MSH or Org.2766. Oral administration of Org.2766 was ineffective. Local application of Org.2766, achieved by wrapping a peptide-impregnated biodegradable gelatine foam matrix around the site of injury, facilitated recovery as well. The biodegradable microspheres and gelatine foam matrix may be of importance in eventual clinical use as effective vehicles for administration of melanocortins in the treatment of peripheral nerve damage.

Experimental grafting of the round window membrane: Part I

The histology and permeability of cats' round window membranes were described following surgical grafting with gelatin foam or fascia. An increase in the thickness of the round window membrane due to fibrosis, neovascularization, and epithelial metaplasia was observed 2 months following grafting with gelatin foam. Grafting with fascia did not increase the thickness of the round window membrane, but did form a thick layer of granulation tissue adjacent to and overlying the window membrane, with occasional adhesions between. The layer of granulation tissue consisted of cuboidal or columnar ciliated epithelial cells, fibrous tissue, lipid, and undigested grafted material. The granulation tissue did not always completely cover the round window membranes.

Characterization of gelatin-surfactant interaction by thickness measurements of foam films

The influence of ionic surfactants (sodium-dodecylsulfate and cetyltrimethylammonium-bromide) on the thickness of gelatin foam films was investigated. The thickness of pure gelatin films was found to be 80 to < 100 nm. Maximum thicknesses are obtained within the range of the isoelectrical point. Foam films stabilized by gelatin-surfactant complexes are found to form common black films with a thickness of 8 to 12 nm. When the surfactant concentration exceeds the binding capacity of the gelatin the common black films turn into Newton-black films with a thickness comparable to that of a pure surfactant solution.

Embolization of the liver in the management of metastatic carcinoid tumors.

Eight patients with metastatic carcinoid tumors and the carcinoid syndrome were treated with gelatin foam embolization of the hepatic arterial tree. The aims were to reduce the tumor mass in the liver and to eliminate the carcinoid syndrome. The effects of the treatment were judged from arteriograms, CT scans, and the levels of serotonin in blood and 5-HIAA in urine, as well as from the clinical symptoms. The mean follow-up time was 12.5 months. In all patients the liver tumor mass was reduced after embolization, and this reduction persisted for at least 6 months in seven patients. After treatment, reduced serotonin levels in blood were measured in four patients and reduced 5-HIAA levels in urine in seven patients. In five patients the carcinoid syndrome disappeared after embolization, but after 6 months two of these five patients had regained symptoms. Adverse reactions were minor consisting of a slight fever, reversibly increased serum levels of liver enzymes, and abdominal pain. In our experience, the hepatic embolization is a simple and safe method of giving relief from the carcinoid syndrome.

Comparative evaluation of local hemostatic agents in experimental liver trauma: A study in the rat

The efficacy of gelatin foam, oxidized regenerated cellulose, collagen fleece, and microcrystalline collagen as hemostatic agents was tested after standardized liver trauma in the rat. Experiments were divided into two series. In the first series all the above local hemostatic agents were tested on normal animals. Animals in which surgical gauze was applied to the traumatized surface served as controls. Nontreated animals bled profusely. Microcrystalline collagen and collagen fleece were more effective than gauze. In the second series collagen preparations were tested on animals with hemostatic disorders caused by administration of acetylsalicylic acid, ethanol intoxication, or infusion of bensylpenicillin. Collagen preparations were as effective as gauze in diminishing bleeding time and blood loss after liver trauma.

Gelfoam powder embolization of the left gastric artery in treatment of massive small-vessel gastric bleeding.

Gelfoam (gelatin foam) powder was used for embolization therapy of massive gastric bleeding from small vessels in 14 patients with severe underlying medical problems. Bleeding was controlled in 10 patients with lesions localized in areas supplied by the embolized left gastric artery. In four patients with concurrent lesions in other portions of the stomach, bleeding decreased only (3 patients) or did not respond to embolization (1 patient). Complications developed in 2 patients with compromised vascular supply of the stomach: superficial ischemic ulcers that healed, and a large ulcer that perforated and required surgery. Microscopic studies demonstrated Gelfoam powder penetration mostly into vessels 100 to 200 microns in diameter and only occasionally into smaller vessels 50 to 60 microns, with occlusion of approximately 10 to 15% of the vasculature. It is concluded that Gelfoam fragments are the primary embolic material to be used for occlusion of the left gastric artery. Use of Gelfoam powder should be limited to occasional patients who have only little chance of responding to Gelfoam fragment embolization. Potential candidates for Gelfoam powder embolization include patients with major coagulopathies and/or uremia who massively hemorrhage from small-vessel lesions localized in upper portions of the stomach, exhibit significant mucosal hypervascularity, and do not respond to selective vasopressin treatment. An uncompromised vascular supply of the stomach is a precondition of a safe left gastric artery embolization.

Prevention of postlaminectomy scar formation.

An animal experimental study was performed to investigate prevention of scar formation under lumbar laminectomy by using new biodegradable interposing materials-- polylactic acid (PLA) foam and membrane. The experimental animals consisted of 32 dogs, 16 control and 16 experimental. The experimental surgery consisted of L5 or L6 complete laminectomy and covering of the laminectomy defect with the experimental materials. The same procedure but without the covering of the laminectomy defect was performed on the control group animals. Animals were sacrificed at varying intervals (2-52 weeks) and the lumbar spines were evaluated with histologic preparations. The PLA membrane is found to be a promising material for prevention of scar tissue extension and adhesion after laminectomy but has a problem of marginal fitting. PLA foam is found to behave as a scaffold for scar tissue extension and adhesion onto the nerve. Other foamy materials such as gelatin foam or avitane are probably behaving similarly, causing scar tissue extension and adhesion. The new materials were found to be completely biocompatible and slowly biodegradable. A combined use of posteriorly convexed stiff PLA membrane and marginal gap filler with PLA foam may provide solutions for both prevention of scar tissue extension and adhesion and prevention of postlaminectomy spinal stenosis.

Gelfoam paste in experimental laminectomy and cranial trephination: hemostasis and bone healing.

The hemostatic properties and effect on osteogenesis of gelatin foam paste and bone wax were compared on surgical bone lesions in experimental animals. Thirty rabbits each received four trephine craniotomies and four lumbar laminectomies. Alternate bone incisions in each animal were treated with either gelatin foam paste or bone wax. Blood loss was measured by absorbing the blood into dry surgical cottonoids weighed before and after use. Bone healing sites of three rabbits were examined histologically to assess the effect of each agent on osteogenesis. The trephination sites of eight rabbits were subjected to fracture force testing at 6 weeks postoperatively to compare the effect ot the two agents on bone healing. No significant difference was found between gelatin foam paste and bone wax in either effectiveness of hemostasis or effect on osteogenesis.

Control of postlaminectomy scar formation: an experimental and clinical study.

Scar formation after laminectomy was evaluated in dogs treated with hemostatic agents, antiinflammatory drugs, or mechanical barriers. Microfibrillar collagen was found to be superior to gelatin foam. The antiinflammatory drugs delayed healing and frequently resulted in abscess formation, and eventually scar filled the defect. The fat grafts formed a viable mechanical barrier. Gelatin foam sponge was compared with microfibrillar collagen for hemostasis with free fat grafts in a clinical series of 50 patients. The latter technique was clearly superior.

Use of microfibrillar collagen as a topical hemostatic agent in brain tissue

Microfibrillar collagen, a recently introduced topical hemostatic agent, was used to obtain hemostasis in suction-evacuation lesions of canine cortex. Gelatin foam was used as a control in identical lesions on the opposite side. Microfibrillar collagen was found to be faster acting and more effective than gelatin foam. Histological evaluation of the lesions at 2,4, and 6 months postoperatively showed no significant difference in the amount or type of tissue reaction to the two agents.

Topical hemostatic agents to reduce bleeding from cancellous bone. A comparison of microcrystalline collagen, thrombin, and thrombin-soaked gelatin foam

In fifty-three dogs microcrystalline collagen, thrombin-soaked gelatin foam, and thrombin powder were evaluated as hemostatic agents when applied to bleeding cancellous surfaces after osteotomy of the greater trochanter using two quantitative models: one, a single osteotomy; the other, a double osteotomy. All three agents significantly reduced bleeding compared with the controls, the microcrystalline collagen being most effective. At three months there was no evidence that microcrystalline collagen and thrombin-gelatin interfered with bone healing after the greater trochanter was reattached with two wires.

An autoradiographic investigation of the projection of the vomeronasal organ to the accessory olfactory bulb in the mouse

Autoradiographic labelling was used to investigate the primary olfactory projections in the mouse. Small pieces of gelatin foam soaked in [ 3H]proline were inserted directly into the cavity of the vomeronasal organ. At survival times from 6 h to 10 days, radioactive label was found over the vomeronasal nerves and the glomeruli of the accessory olfactory bulb. Conversely, when radioactive amino acid was applied to the main olfactory mucosa, the label appeared over the main olfactory nerves and the glomeruli of the main olfactory bulb. In both the main and accessory bulbs there was evidence for a transneuronal uptake of label in the external plexiform and mitral cell layers subjacent to the labelled glomeruli. This transneuronal uptake was heavier at longer survival periods.

High-frequency establishment of human immunoglobulin-producing lymphoblastoid lines from normal and malignant lymphoid tissue and peripheral blood.

AbstractHuman hematopoietic tissue and lymphocytes separated from 10‐20 ml samples of peripheral blood have been grown in vitro in a lens‐paper and a gelatin foam (Spongostan) grid organ culture.Lymphoblastoid cell lines were established from the lymph nodes, and in one case from the spleen, of 22/23 consecutive, unselected adult individuals without manifest malignancy or infectious mononucleosis. Biopsies from 5/8 patients with malignancy were successful. The blood tines were derived from 5/10 patients with and 4/10 donors without malignancy.The very high frequency of success from normal tissue confirms the assumption made before that the spontaneous establishment of lymphoblastoid cell lines is unrelated to manifest malignancy of the donor. The results indicate that lymphoid cells with a potential for infinite proliferation (“lymphoblastoid transformation”) are present in almost all adult individuals. The Spongostan grid culture is a superior instrument to select and/or adapt these cells in vitro.All lymphoblastoid lines produced immunoglobulins. The majority started with a “polyclonal” pattern of immunoglobulin production but changed towards stable “ monoclonality “ during the course of long‐term cultivation. It is suggested that lymphoblastoid lines have a polyclonal origin and that the reason for development of a monoclonal line is a selection of one cell clone either in the organ culture during establishment or in long‐term culture.

Histological changes in long term explants of human lymph nodes during lymphoblastoid transformation.

The sequence of events in long‐term cultures in lymph node fragments and in underlying three dimensional matrix of gelatin foam (Spongostan) has been studied histologically. Lymphoid cells together with reticulum‐like cells survived excellently in the periphery of the original lymph node fragments until the time of lymphoblastoid transformation 8 weeks after explantation. The centre of the lymph node became increasingly fibroid from the third week onwards. The Spongostan matrix was gradually converted to an organotypic structure where lymphoid cells survived and proliferated. During week 3–6 after explantation only few lymphoid cells were discharged into the medium. At the same time, however, the number of such cells did not decline within the explant. The diminished release could thus not be explained by increased lymphoid cell death at their source of origin, i. e. the original explant. The findings support that lymphoblastoid cells go through a phase of adaptation within the explant.

Respiratory and circulatory effects of 100 meq-l potassium or 2 per cent procaine in the cerebrospinal fluid of cats.

In cats lightly anesthetized with chloralose-urethane, the ventral surface of the medulla was perfused with mock CSF of different potassium concentrations, or with solutions containing 2% procaine. In some experiments a wall of gelatin foam glued onto the midline of the medulla allowed a separate perfusion of either half of the medullary surface. To study the blockade of different layers of the medullary tissue, electrical stimuli were applied at varying depths from the ventral surface, at a spot located medially from the roots of the hypoglossal nerve and 3 mm laterally from the midline. 1. Both potassium at 100 meq/l, and 2% procaine, cause respiratory arrest after 50–650 sec when perfused over the ventral medullary surface. 2. Perfusion of one half of the ventral medullary surface with potassium at 100 meq/l, the opposite half being perfused simultaneously with reference solution, causes a decrease in ventilation of more than 50% and in some cases respiratory arrest. 3. Electrical stimuli (1 V; 60 sec−1) 200 μ below the surface cause a slight inspiratory displacement of the respiratory leve, and later an increase in tidal volume and frequency. When the medullary surface is perfused either with the solution of high potassium concentration, or with 2% procaine, the response to these stimuli disappears at about the time of respiratory arrest. 4. The response to electrical stimuli (0.5 V; 60 sec−1) applied 1.5 mm below the surface — a vigorous inspiration followed by apneusis in extreme inspiratory position — outlasts for several minutes the respiratory arrest induced by perfusion with 100 meq/l potassium. 5. Potassium at 100 meq/l causes a transitory fall in blood pressure; later the blood pressure rises above the control level During perfusion with 2% procaine, the blood pressure usually decreases and remains on this low level until the drug is washed out.

Successful use of gelatin foam sponge in surgical restoration of fertility

Successful use of gelatin foam sponge in surgical restoration of fertility

The use of powdered gelatin foam in the treatment of vascular ulcers.

The use of powdered gelatin foam in the treatment of vascular ulcers.