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Gel matrix vehicles for growth factor application in nerve gap injuries repaired with tubes: a comparison of biomatrix, collagen, and methylcellulose.

The repair of nerve gap injuries with tubular nerve guides has been used extensively as an in vivo test model in identifying substances which may enhance nerve regeneration. The model has also been used clinical nerve repair. The objective of this study was to compare three different gel matrix-forming materials as potential vehicles for growth factors in this system. The vehicles included a laminin containing extracellular matrix preparation (Biomatrix), collagen, and a 2% methylcellulose gel. The growth factor test substance consisted of a combination of platelet-derived growth factor BB (PDGF-BB) and insulin-like growth factor I (IGF-I). An 8-mm gap in rat sciatic nerve was repaired with a silicone tube containing each of the vehicles alone or with a combination of each vehicle plus PDGF-BB and IGF-I. At 4 weeks after injury, the application of the growth factor combination significantly stimulated axonal regeneration when applied in methylcellulose or collagen, but not in Biomatrix. A similar trend was present between the vehicle control groups. By 8 weeks after injury, nerves repaired with methylcellulose as a vehicle had significantly greater conduction velocity than either collagen or Biomatrix. It was concluded that a 2% methylcellulose gel was the best of the three matrices tested, both in its effects on nerve regeneration and flexibility of formulation.

Animals↗

Clinical evaluation of methylcellulose as a bulk laxative.

We studied a bulk laxative containing methylcellulose in a group of normal subjects as well as in a group of chronically constipated individuals. The initial study in normal subjects was performed to show that the compound could increase fecal weight without significant side effects. Fifty healthy subjects were studied. Methylcellulose in daily doses of 4 g demonstrated a statistically significant increase in fecal frequency, fecal water, and fecal solids. In the second phase, we studied a group of 59 chronically constipated individuals treated with daily doses of the laxative containing either 1, 2, or 4 g of methylcellulose or 3.4 g psyllium. All of these doses resulted in statistically significant increases in stool frequency, water content, and fecal solids. There was no increase in individual stool weight from any of the laxative doses. Methylcellulose, in a daily dose as low as 1 g, is an effective laxative.

Adolescent↗

Methylcellulose during cryopreservation of ventral mesencephalic tissue fragments fails to improve survival and function of cell suspension grafts.

Cryopreservation may allow long-term storage of fetal ventral mesencephalon (VM) for transplantation in patients suffering from Parkinson's disease (PD). We investigated whether the polymer methylcellulose protects fetal rat VM during cryopreservation in liquid nitrogen and improves survival and function of this tissue as intrastriatal suspension grafts in the 6-hydroxydopamine (6-OHDA) rat model. VM tissue fragments (E14-E15) were either immediately dissociated and grafted as a cell suspension (FRESH) or cryopreserved under controlled conditions for 7 days in a conventional cryoprotective medium (CRYO) or a medium containing 0.1% methylcellulose (mCRYO) and then dissociated and grafted. Rats from the cryo-groups showed only limited behavioral compensation in contrast to complete compensation observed in rats from the FRESH group. Cryopreservation of fetal rat VM decreased the viability of cell suspensions in vitro to about 70%, survival of grafted tyrosine hydroxylase-immunoreactive (TH-IR) neurons to 11% and 20%, and transplant volume to 8% and 17% (mCRYO and CRYO, respectively, compared to FRESH). The addition of 0.1% methylcellulose to tissue fragments during freezing did neither improve in vitro viability nor survival of TH-IR neurons nor behavioral compensation when compared to the control CRYO group. These results suggest that methylcellulose failed to improve survival of cryopreserved dopaminergic ventral mesencephalic neurons.

Analysis of Variance↗

Effects of methylcellulose on hepatic glutathione levels and plasma ALAT following single oral administration to male Bom:NMRI mice.

1. A single p.o. dose of 1% w/v methylcellulose 0.013 ml/kg was given to male Bom:NMRI mice using untreated animals as controls. 2. A circadian fluctuation was seen in the hepatic glutathione levels (GSH) of both the methylcellulose and untreated animal group. 3. The methylcellulose administration did not affect the hepatic GSH or plasma ALAT level compared to untreated animals. 4. Histological examination did not reveal any abnormalities of the stomach wall, liver or kidney during the 12 hr trial period. 5. Male Bom:NMRI mice treated with 1% w/v methylcellulose can be considered representative of untreated controls in short-term experiments studying liver GSH and plasma ALAT levels.

Alanine Transaminase↗

The effects of sodium hyaluronate, chondroitin sulfate, and methylcellulose on the corneal endothelium and intraocular pressure.

Sodium hyaluronate (Healon), chondroitin sulfate, and methylcellulose have been used to protect the corneal endothelium from intraocular lens trauma. A study of the efficacy and toxicity of these compounds showed that 1% sodium hyaluronate, 0.4% methylcellulose, and 20% chondroitin sulfate were nontoxic to the corneal endothelium, but that 20% chondroitin sulfate caused a marked decrease in corneal thickness because of its hypertonicity. Anterior chamber injection of these viscous substances resulted in an increase in intraocular pressure. Within one to four hours the maximum intraocular pressure with 1% sodium hyaluronate was 67 +/- 4.1 mm Hg and that with 20% chondroitin sulfate was 55 +/- 3.5 mm Hg. The intraocular pressure did not increase to these high levels with 10% chondroitin sulfate or 0.4% methylcellulose or when the test substances were washed out of the anterior chamber. The corneal endothelium was protected from injury with 1% sodium hyaluronate and 20% chondroitin sulfate, but 10% chondroitin sulfate and 0.4% methylcellulose provided only minimal protection.

Animals↗

Comparison of the protective effects of methylcellulose and sodium hyaluronate on corneal swelling following phacoemulsification of senile cataracts.

The protective effects of two viscoelastic substances (hydroxypropyl methylcellulose and sodium hyaluronate) on the cornea during phacoemulsification of senile cataracts were investigated in a prospective, randomized, clinical study. The viscoelastic substances were placed in the anterior chamber before and during phacoemulsification. The mean increase in central corneal thickness (measured by ultrasonic pachymetry) on the first postoperative day was statistically significantly higher (P less than .05) in the methylcellulose group (35 eyes) than in the sodium hyaluronate group (35 eyes). Five weeks postoperatively the difference in mean central corneal thickness between the two groups was not statistically significant. However, one eye in the methylcellulose group developed bullous keratopathy. The present study indicates that methylcellulose does not protect the corneal endothelium as effectively as sodium hyaluronate during phacoemulsification procedures.

Aged↗

Influence of beta-cyclodextrin complexation on carbamazepine release from hydroxypropyl methylcellulose matrix tablets.

The in vitro release profiles of carbamazepine and beta-cyclodextrin either complexed or simply mixed and subsequently incorporated in hydrophilic matrix tablets containing 15 or 30% hydroxypropyl methylcellulose were evaluated. Solubility studies revealed a linear relationship between the increase in carbamazepine solubility and the increase in beta-cyclodextrin concentration. Drying methods (spray-drying and freeze-drying) were used to obtain carbamazepine/beta-cyclodextrin solid complexes in order to prepare tablets. The results demonstrated that matrix tablets containing carbamazepine/beta-cyclodextrin solid complexes displayed faster carbamazepine and beta-cyclodextrin release compared to that containing simple physical mixture. Gelling and matrix formation was impaired in formulation containing 15% hydroxypropyl methylcellulose and spray-dried complex. The comparison of spray-drying and freeze-drying revealed no significant influence of both drying methods on carbamazepine and beta-cyclodextrin dissolution rate when carbamazepine/beta-cyclodextrin complexes were incorporated in 30% hydroxypropyl methylcellulose matrix tablets. The results point to the possibility of modulating carbamazepine release using a hydroxypropyl methylcellulose matrix associated to the drug complexed with beta-cyclodextrin.

Anticonvulsants↗

Prevention of fungal colonization and digestion of cellulose by the addition of methylcellulose.

When the attachment of cellulolytic rumen fungi to cellulose is blocked by the addition of methylcellulose, cellulose digestion is entirely inhibited. Even after these fungi have colonized and penetrated the cellulosic fibers of filter paper, the addition of methylcellulose effectively halts cellulose digestion. This effect of methylcellulose is accompanied by the complete inhibition of fungal attachment to cellulose fibers; the addition of methylcellulose does not affect the growth of these organisms on soluble substrates. We conclude that fungal cellulose digestion, like bacterial cellulose digestion, requires the spatial juxtaposition of the cellulolytic organism and its insoluble substrate. The simultaneous inhibition of both attachment and digestion by the same inhibitor suggests that these two processes are functionally linked in the fungi.

Animals↗

[Application of 2% clindamycin cream in the treatment of bacterial vaginosis and valuation of methylcellulose gel containing the complex of Chitosan F and PVP k-90 with lactic acid as carrier for intravaginally adhbited medicines in the cases of pregnancies with the symptoms of preterm delivery].

OBJECTIVES: There are many reports informing about the connection between BV and the increased risk of preterm delivery. The reason of self-concession and reversion of BV after having executed an efficient treatment has not yet been properly explained. DESIGN: The aim of this work was the clinical valuation of the 2% Clindamycin cream in the treatment of BV and of the methylcellulose gel containing the complex of Chitosan F and PVP K-90 with lactic acid as a carrier for intravaginally adhbited medicines in the cases of pregnancies with the symptoms of a preterm delivery. MATERIAL AND METHODS: The research comprised 145 pregnant between 24-34 week of pregnancy, hospitalised because of the symptoms of a preterm menace delivery. In the case of the detection of BV, a 10-day therapy using intravaginal cream containing 2% Clindamycin was executed. In the cases not qualified as BV, the methylcellulose gel containing the complex of Chitosan F and PVP K-90 with lactic acid has been intravaginally adhibited for 10 days. CONCLUSIONS: 1. Application of 2% Clindamycin cream is an efficient method of the treatment of bacterial vaginosis. 2. Methylcellulose gel containing lactic acid combined with the complex of Chitosan F and PVP K-90 allows a persistent maintenance of the correct pH of vagina. 3. Methylcellulose gel, because of its physico-chemical properties similar to physiological mucus, is a universal carrier for intravaginally adhibited medicines.

Administration, Intravaginal↗

[Coating of artificial lens with methylcellulose (author's transl)].

The corneal haze which in the past often followed lens implantation was clearly decreased by applying one drop of a 1% solution of methylcellulose into the lens immediately prior to its insertion. It is surmised that by coating the lens in this way injury to the corneal endothelium is prevented. Methylcellulose caused little if any rise of intraocular pressure postoperatively.--The preparation of a sterile solution of methylcellulose is described in detail. Finally, it is important to stress that--in addition to applying methylcellulose--one should always attempt to work under an air bubble.

Cataract Extraction↗

Methylcellulose protects the ability of anchorage-dependent cells to adhere following isolation and holding in suspension.

Preparation of suspension of anchorage-dependent cells growing in tissue cultures requires removal of the cells from their substrata by means of trypsin and/or EDTA. The purpose of the experiments was to investigate the effect of methylcellulose on the adhesive ability of cells removed from substrata by EDTA and trypsin. Human umbilical cord vein endothelial cells (HUVEC), after detachment from substrata, adhere well to fibronectin at 37 degrees C but not at 0 degrees C. During a 60-min incubation at 37 degrees C, these cells lose about 70% of their ability to adhere to fibronectin. The ability of cells to adhere was restored in the presence of 0.2% methylcellulose. Methylcellulose also prevented human skin fibroblasts, human melanoma cells and mouse lung fibroblasts from losing adhesive properties. By contrast, it did not affect the adhesive ability of B16F10 melanoma cells incubated at 37 degrees C. In conclusion, our study suggests that methylcellulose can be a useful reagent for preservation of cell function in suspension; it may also simplify some experimental procedures including radioiodination of cell surface components and cross-linking of radiolabeled ligands to the cell surface.

Animals↗

Inhibitory Effects of Methylcellulose on Cellulose Degradation by Ruminococcus flavefaciens.

Highly methylated, long-chain celluloses strongly inhibited cellulose degradation by several species of cellulolytic bacteria of ruminal origin. Specifically, the inhibitory effects of methylcellulose on the growth of Ruminococcus flavefaciens FD1 were concentration dependent, with complete inhibition at 0.1% (wt/vol). However, methylcellulose did not inhibit growth on cellobiose or cellulooligosaccharides. Mixtures of methylated cellulooligosaccharides having an average degree of polymerization of 6.7 to 9.5 inhibited cellulose degradation, but those with an average degree of polymerization of 1.0 to 4.5 did not. Similar inhibitory effects by methylcellulose and, to a lesser extent, by methyl cellulooligosaccharides were observed on cellulase activity, as measured by hydrolysis of p-nitrophenyl-beta-d-cellobioside. R. flavefaciens cultures hydrolyzed cellulooligosaccharides to cellobiose and cellotriose as final end products. Cellopentaose and cellohexaose were cleaved to these end products, but cellotetraose was also formed from cellohexaose. Methylcellulose did not inhibit hydrolysis of cellulooligosaccharides. These data are consistent with the presence of separate cellulase (beta-1,4-glucanase) and cellulodextrinase activities in R. flavefaciens.

Journal Article↗

Sideroblastic anemia: differences in bone marrow erythroid colony (CFUE) growth responses to erythropoietin in plasma clot and methylcellulose cultures.

Bone marrow cells from three patients with idiopathic acquired sideroblastic anemia and one with X-linked sideroblastic anemia were simultaneously cultured in plasma clot and methylcellulose cultures in order to evaluate their erythroid colony (CFUE) cloning potential in these two systems. In contrast to normals, sideroblastic anemia bone marrow cells demonstrated a marked ability to form erythropoietin (Epo)-independent CFUE in methylcellulose culture, and were inhibited in their ability to generate CFUE in plasma clot culture even in the presence of Epo. Addition of citrated plasma to methylcellulose cultures inhibited Epo-independent CFUE growth, but not Epo-dependent growth, by both a normal and patients' bone marrow cells. These results demonstrate that bone marrow cells from some patients with sideroblastic anemia can undergo Epo-independent and Epo-dependent CFUE growth in vitro, and that there is a marked difference in CFUE growth depending on the type of clonal culture method used. It is suggested that the culture microenvironment, plasma, and sensitivity to Epo may be contributing factors which allow specific clones of sideroblastic anemia CFUE-forming cells to proliferate in vitro.

Anemia, Sideroblastic↗

Tumor colony formation from human spontaneous tumors in a methylcellulose monolayer system.

A methylcellulose monolayer system is described that facilitates the "in vitro" cultures of human spontaneous tumor cells. The tumor samples were disaggregated mechanically and cultured in 0.9% methylcellulose with 30% fetal calf serum in Iscove's modified Dulbecco's medium. Eighty-five individual tumor samples with different histological types were seeded, 45 gave rise to tumor cell colonies. The plating efficiency ranged from 0.02% to 0.22%. Cytologic and cytochemical staining from aspirated cells revealed the same morphology of cells as the cells in the suspension. A flattening of colonies, as it has been described by others using methylcellulose monolayer, was not observed.

Clone Cells↗

Preparation of buccal patch composed of carbopol, poloxamer and hydroxypropyl methylcellulose.

A polymeric film composed of Carbopol, Poloxamer and hydroxypropyl methylcellulose was prepared to develop a buccal patch and the effects of composition of the film on adhesion time, swelling ratio, and dissolution of the film were studied. The effects of plasticizers or penetration enhancers on the release of triamcinolone acetonide (TAA) were also studied. The hydrogen bonding between Carbopol and Poloxamer played important role in reducing swelling ratio and dissolution rate of polymer film and increasing adhesion time. The swelling ratio of the composite film was significantly reduced and the adhesion time was increased when compared with Carbopol film. As the ratio of Poloxamer to hydroxypropyl methylcellulose increased from 0/66 to 33/33, the release rate of TAA decreased. However, no further significant decrease of release rate was observed beyond the ratio of 33/33. The release rate of TAA in the polymeric film containing polyethylene glycol 400, a plasticizer, showed the highest release rate followed by triethyl citrate, and castor oil. The release rate of TAA from the polymeric film containing permeation enhancers was slower than that from the control without enhancers. Therefore, these observations indicated that a preparation of a buccal patch is feasible with the polymeric film composed of Cabopol, Poloxamer and hydropropyl methylcellulose.

Acrylic Resins↗

Multidetector CT enteroclysis versus barium enteroclysis with methylcellulose in patients with suspected small bowel disease.

The purpose of this study was to evaluate the diagnostic accuracy of multidetector-CT enteroclysis (MDCT-E) versus barium enteroclysis with methylcellulose (BE) in clinically selected patients with suspected small bowel disease. We prospectively studied 52 patients who underwent unenhanced and contrast-enhanced multidetector CT (16 rows) after administration of 2-2.5 l of methylcellulose by naso-jejunal tube. BE was performed after administration of barium 60% w/v (200-250 ml) and methylcellulose (1-2 l). Patients with radiological signs of Crohn's disease were classified into the following subtypes: active, fibrostenotic, fistulising/perforating, reparative or regenerative subtypes. Twenty-eight patients also underwent endoscopy. The radiological prevalent subtype was the active subtype. The sensitivity, specificity and diagnostic accuracy of MDCT-E versus BE was 83%, 100% and 89%, respectively. BE showed five false negative CT cases due to early Crohn's disease; endoscopy confirmed positive cases of the CT and the BE, but showed one false negative case of the BE. Together, MDCT enteroclysis and BE permitted the diagnosis of Crohn's disease in 30 patients, adhesions in one patient, lymphoma in two patients and carcinoid tumours in two patients. In conclusion, MDCT-E permits good representation of pathological patterns. Early stages of Crohn's disease are better evaluated by BE.

Adult↗

The use of hydroxypropyl methylcellulose in extracapsular cataract extraction with intraocular lens implantation.

We conducted a prospective randomized clinical trial on the use of 2% hydroxypropyl methylcellulose and 1% sodium hyaluronate in the anterior chamber during anterior capsulotomy and nuclear expression in extracapsular cataract extraction with posterior chamber lens implantation in 70 patients. Both viscoelastic substances helped maintain the anterior chamber and facilitated the operation, although sodium hyaluronate was preferred. There was no excessive intraocular inflammation or toxicity noted with either agent. Patients given sodium hyaluronate had a larger increase in intraocular pressure during the early postoperative period (2.04 mm Hg) than did those given hydroxypropyl methylcellulose (1.1 mm Hg), but the difference was not significant. Nine weeks after surgery, the mean (+/- SD) central endothelial cell loss was 4.84% (+/- 7.26%) in the 17 eyes with sodium hyaluronate and 4.37% (+/- 9.84%) in the 53 eyes with hydroxypropyl methylcellulose. The intraocular pressure and corneal thickness were not significantly different before operation and nine weeks after it.

Anterior Chamber↗

Effects of recombinant G-CSF and GM-CSF on the growth in methylcellulose and suspension of the blast cells in acute myeloblastic leukemia.

The effects of two recombinant human CSFs (G-CSF and GM-CSF) on the growth of blast progenitors from 36 acute myeloblastic leukemia patients were studied in methylcellulose and suspension cultures. Blast colony formation in methylcellulose and the growth of blast progenitors in suspension were stimulated by G-CSF or GM-CSF. Their responses to CSFs were different from those of normal myeloid progenitors. First, the sensitivity of blasts to 0.01 ng/ml of G-CSF and 0.001 ng/ml of GM-CSF was significantly increased compared with normal. Second, in more than 70% of patients, the pattern of the responsiveness to the two CSFs was aberrant compared with ordered response in normal subjects. Third, in about half of the patients, combination of G-CSF and GM-CSF showed synergism for the growth of blast progenitors in both culture methods, whereas negligible or no synergism was observed in normal subjects. Finally, when stimulated by G-CSF, GM-CSF, or both, a significant relationship was noted between blast colony formation in methylcellulose and blast progenitor growth in suspension, suggesting that CSFs do not affect the balance between self-renewal and terminal divisions of blast stem cells.

Adult↗