RESUMO
The aim of this research was to develop immediate release tablets comprising solid dispersion (IRSDTs) of tadalafil (Td) in a vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA), characterized by improved dissolution profiles. The solid dispersion of Td in PVP-VA (Td/PVP-VA) in a weight ratio of 1:1 (w/w) was prepared using two different processes i.e. spray drying and ball milling. While the former process has been well established in the formulation of IRSDTs the latter has not been exploited in these systems yet. Regardless of the preparation method, both Td/PVP-VA solid dispersions were amorphous as confirmed by PXRD, DSC and FTIR. However, different morphology of particles (SEM) resulted in differences in water apparent solubility and disk intrinsic dissolution rate (DIDR). Both solid dispersions and crystalline Td were successfully made into directly compressible tablets at three doses of Td, i.e. 2.5mg, 10mgand20mg, yielding nine different formulations (D1-D9). Each of the lots met the requirements set by Ph.Eur. and was evaluated with respect to appearance, diameter, thickness, mass, hardness, friability, disintegration time and content of Td. IRSDTs performed as supersaturable formulations and had significantly improved water dissolution profiles in comparison with equivalent tablets containing crystalline Td and the marketed formulations. Tablets with both spray dried and ball milled Td/PVP-VA revealed the greatest improvement in dissolution depending on the investigated doses, i.e. 2.5mgand20mg, respectively. Also, dissolution of Td from Td/PVP-VA delivered in different forms occurred in the following order: powders>tablets>capsules.
Assuntos
Composição de Medicamentos/métodos , Pirrolidinas/química , Comprimidos/química , Tadalafila/química , Compostos de Vinila/química , Varredura Diferencial de Calorimetria , Força Compressiva , Cristalização , Dessecação , Estabilidade de Medicamentos , Microscopia Eletrônica de Varredura , Pós , Solubilidade , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
The aim of this paper was to evaluate physical stability of solid dispersions in respect to the drug, tadalafil (Td), in vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA). Nine solid dispersions of Td in PVP-VA (Td/PVP-VA) varied in terms of quantitative composition (1:9-9:1, w/w) were successfully produced by spray-drying. Their amorphous nature, supersaturated character and molecular level of mixing (a solid solution structure) were subsequently confirmed using DSC, PXRD, SEM and calculation of Hansen total solubility parameters. Due to thermal degradation of both components before the melting point of Td (302.3°C), an approach based on the drug crystallization from the supersaturated solid dispersion was selected to calculate the solubility of Td in the polymer. Annealing of the Td/PVP-VA solid dispersion (1:1, w/w) at selected temperatures above its Tg resulted in different stable solid dispersions. According to the Gordon-Taylor equation their new Tgs gave the information about the quantitative composition which corresponded to the thermodynamic solubility of Td in PVP-VA at given temperatures of annealing. The obtained relationship was fitted to the exponential function, with the calculated solubility of Td of 20.5% at 25°C. This value was in accordance with the results of hot stage polarizing light microscopy as well as stability tests carried out at 80°C and 0% RH, in which Td solid dispersions containing 10-20% of the drug were the only systems that did not crystallize within two months. A thermal analysis protocol utilizing a fast heating rate was shown to generate Td solubility data complementing the solid dispersion method. The Flory-Huggins model applied for the Td/PVP-VA system yielded the solubility value of 0.1% at 25°C, showing the lack of applicability in this case.
Assuntos
Excipientes/química , Inibidores da Fosfodiesterase 5/química , Pirrolidinas/química , Tadalafila/química , Vasodilatadores/química , Compostos de Vinila/química , Fenômenos Químicos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Temperatura Alta/efeitos adversos , Inibidores da Fosfodiesterase 5/administração & dosagem , Solubilidade , Suspensões , Tadalafila/administração & dosagem , Termodinâmica , Temperatura de Transição , Vasodilatadores/administração & dosagemRESUMO
To improve solubility of tadalafil (Td), a poorly soluble drug substance (3µg/ml) belonging to the II class of the Biopharmaceutical Classification System, its six different solid dispersions (1:1, w/w) in the following polymers: HPMC, MC, PVP, PVP-VA, Kollicoat IR and Soluplus were successfully produced by freeze-drying. Scanning electron microscopy showed a morphological structure of solid dispersions typical of lyophilisates. Apparent solubility and intrinsic dissolution rate studies revealed the greatest, a 16-fold, increase in drug solubility (50µg/ml) and a significant, 20-fold, dissolution rate enhancement for the Td/PVP-VA solid dispersion in comparison with crystalline Td. However, the longest duration of the supersaturation state in water (27µg/ml) over 24h was observed for the Td solid dispersion in HPMC. The improved dissolution of Td from Td/PVP-VA was confirmed in the standard dissolution test of capsules filled with solid dispersions. Powder X-ray diffraction and thermal analysis showed the amorphous nature of these binary systems and indicated the existence of dispersion at the molecular level and its supersaturated character, respectively. Nevertheless, as evidenced by film casting, the greatest ability to dissolve Td in polymer was determined for PVP-VA. The crystallization tendency of Td dispersed in Kollicoat IR could be explained by the low Tg (113°C) of the solid dispersion and the highest difference in Hansen solubility parameters (6.8MPa(0.5)) between Td and the polymer, although this relationship was not satisfied for the partially crystalline dispersion in PVP. Similarly, no correlation was found between the strength of hydrogen bonds investigated using infrared spectroscopy and the physical stability of solid dispersions or the level of supersaturation in aqueous solution.
Assuntos
Derivados da Hipromelose/química , Pirrolidinas/química , Tadalafila/química , Compostos de Vinila/química , Varredura Diferencial de Calorimetria , Cápsulas , Química Farmacêutica , Cristalografia por Raios X , Estabilidade de Medicamentos , Liofilização , Ligação de Hidrogênio , Cinética , Microscopia Eletrônica de Varredura , Difração de Pó , Pós , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tecnologia Farmacêutica/métodos , TemperaturaRESUMO
The evaluation of incidence of bone formation by whole syngeneic bone marrow cell suspension and by bone marrow stromal cell cultured in vitro injection into kidney parenchyma was done. Bone tissue was found in 26 kidneys out of 100 injected with whole bone marrow cells suspension. Cultured stromal bone marrow cells grafted into kidney parenchyma produced ossicles in only 4 out of 101 injected kidneys. Such low incidence of bone forming ability of the marrow stromal cell cultures grafted into kidney indicate their useless for study on bone histogenesis in the kidney by murine marrow stromal cell cultures.
RESUMO
The purpose of this paper is to examine the role of molecular mobility in the recrystallization process from the amorphous state of the anticholesterol drug ezetimibe. Both the molecular dynamics and crystallization kinetics have been studied using various experimental techniques, such as broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Our investigations have shown that ezetimibe easily recrystallizes from the disordered state, both below and above its glass transition temperature (Tg = 336 K). Moreover, we found that an only slightly elevated pressure (5 MPa) significantly accelerates the recrystallization process at T > Tg. We predict that the structural relaxation time of amorphous ezetimibe at 293 K (storage temperature) and ambient pressure is only 22 days. This result corresponds to the characteristic time, determined from XRD measurements, for amorphous ezetimibe to recrystallize during storage at Troom = 298 K. It leads to the conclusion that the molecular mobility reflected in structural relaxation of ezetimibe is mainly responsible for devitrification of this drug. Finally, we determined a relatively easy way to improve the physical stability of the drug by preparing a binary amorphous ezetimibe-Soluplus mixture. Ezetimibe in an amorphous mixture with 20 wt % Soluplus has a much better (over six times) solubility than the pure crystalline material.
Assuntos
Anticolesterolemiantes/química , Azetidinas/química , Estabilidade de Medicamentos , Simulação de Dinâmica Molecular , Varredura Diferencial de Calorimetria , Cristalização , Espectroscopia Dielétrica , Ezetimiba , Cinética , Temperatura de Transição , Difração de Raios XRESUMO
This study for the first time investigates the solubility and dissolution rate of amorphous tadalafil (Td)--a poorly water soluble chemical compound which is commonly used for treating the erectile dysfunction. To convert the crystalline form of Td drug to its amorphous counterpart we have employed most of the commercially available amorphization techniques i.e. vitrification, cryogenic grinding, ball milling, spray drying, freeze drying and antisolvent precipitation. Among the mentioned methods only quenched cooling of the molten sample was found to be an inappropriate method of Td amorphization. This is due to the thermal decomposition of Td above 200°C, as proved by the thermogravimetric analysis (TGA). Disordered character of all examined samples was confirmed using differential scanning calorimetry (DSC) and X-ray powder diffraction (PXRD). In the case of most amorphous powders, the largest 3-fold increase of apparent solubility was observed after 5 min, indicating their fast recrystallization in water. On the other hand, the partially amorphous precipitate of Td and hypromellose enhanced the solubility of Td approximately 14 times, as compared with a crystalline substance, which remained constant for half an hour. Finally, disk intrinsic dissolution rate (DIDR) of amorphous forms of Td was also examined.
Assuntos
Carbolinas/química , Inibidores da Fosfodiesterase 5/química , Varredura Diferencial de Calorimetria , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tadalafila , Termogravimetria , Difração de Raios XRESUMO
Telmisartan (TLM), a poorly water-soluble angiotensin II receptor antagonist in crystalline form, was transformed into the amorphous state by the melt quench technique, as well as a cryogenic grinding method, in order to improve its physiochemical properties. The chemical stability of TLM, that is, the tendency of the material to resist change or decomposition due to internal reaction, or due to the effects of air, heat, light, pressure, etc., during formation of the amorphous phase was assessed by monitoring high performance liquid chromatography. The existence of the amorphous state was confirmed by differential scanning calorimetry and X-ray powder diffraction. The glass transition occurred at T(g)=401K. In the next stage, the solubility of TLM in 0.1M HCl, phosphate buffer, pH=6.8, and water (25°C and 37°C) was determined. Both amorphous forms of TLM (vitrified and cryogrinded) had a higher solubility (µg/ml) than their crystalline counterpart. An important and interesting problem of the study was to evaluate how the tableting process was affected by the choice of either a crystalline or an amorphous form of TLM. Eight different tablet formulations were evaluated using both the crystalline and the amorphous form of TLM. Measurements of the physical properties and dissolution tests of G4 formulations tablets with telmisartan in crystalline and amorphous form after different storage periods were also performed.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Benzimidazóis/química , Benzoatos/química , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão , Cristalização , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Solubilidade , Comprimidos , Telmisartan , Temperatura , Fatores de Tempo , Difração de Raios XRESUMO
Excessive bone formation occurring in such conditions as paravertebral ligamentous ossification, hallux osteophytes or some neoplastic tumors, presents a significant problem, both epidemiological and clinical. Since pathogenesis of this disorder is still unclear, we studied its mechanism in experimental model utilizing inducible orthotopic osteogenesis. Periosteal bone apposition stimulated by Moloney sarcoma is characterized by unusually high volume of new bone tissue appearing subperiosteally in the bone adjacent to the tumor. Genes engaged in this growth have not been characterized so far. Here we show the results of mRNA Representation Difference Analysis in Moloney sarcoma, which reveal high expression of four genes coding extracellular matrix proteins: osteopontin, fibronectin, stromelysin-1 and tenascin. These findings suggest that the uncommon dynamics of the Moloney sarcoma-induced osteogenesis depends on high expression of these extracellular matrix proteins.
Assuntos
Fibronectinas/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Vírus do Sarcoma Murino de Moloney/fisiologia , Osteogênese/fisiologia , Osteopontina/metabolismo , Periósteo/virologia , Sarcoma Experimental/etiologia , Tenascina/metabolismo , Animais , Northern Blotting , Camundongos , Camundongos Endogâmicos BALB CRESUMO
1. The aim of the present study was to evaluate the influence of fluvastatin (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor) on heterotopic ossification (HO) induced by HeLa cells. 2. C57Bl/6 mice were injected with 3 x 10(6) HeLa cells into right thigh muscles. Mice in the experimental group received fluvastatin 1.2 mg/kg per day for 17 consecutive days, while mice in the control group received placebo. Intact mice served as an additional control. Seventeen days post-HeLa cell grafting, blood samples were collected to measure total serum cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol and alkaline phosphatase (AP). 3. In all animals injected with HeLa cells, the mass of mineral deposited in the induced ossicle was established after hydrolysis of soft tissues surrounding the induced ossicles. In fluvastatin-treated mice, the mass of mineral deposited in heterotopically induced ossicles was significantly increased, when compared to mice receiving placebo. This was followed by a significant decrease of TG concentration; whereas the levels of serum AP were not significantly affected. 4. These results indicate that administration of statins may affect heterotopic ossification. This may also have clinical implication, because patients predisposed to HO and receiving statins during hypocholesterolemic treatment, may be at even greater risk of HO.
Assuntos
Ácidos Graxos Monoinsaturados/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Indóis/farmacologia , Ossificação Heterotópica/induzido quimicamente , Fosfatase Alcalina/metabolismo , Animais , Desenvolvimento Ósseo , Osso e Ossos/patologia , Colesterol/sangue , Fluvastatina , Células HeLa , Humanos , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ossificação Heterotópica/patologiaRESUMO
Syngeneic, allogeneic and xenogeneic (rat) freshly isolated bone marow cells + stromal cell cultures maintained in vitro for 10-30 days, as well as non-adherent cells removed from these cultures on 3rd-4th day were injected into the kidney parenchyma of mice, immunosuppressed with hydrocortisone. In syngeneic grafts the immunosuppression was omitted. In all transplant systems bone tissue was formed inside the kidney with 20% to 32% variation. Bone produced by allogeneic and xenogeneic cells is subject to rejection when immunosuppression ceases, as the bone formed is of donor origin. The "floating" cells, regardless of the transplant system, normally discarded during media replacement, turned out to be efficient bone producers. This notion is of practical implication when bone marrow cells are used for bone healing.
Assuntos
Células da Medula Óssea/citologia , Transplante de Medula Óssea/fisiologia , Osteogênese/fisiologia , Animais , Células da Medula Óssea/fisiologia , Adesão Celular/fisiologia , Diferenciação Celular/fisiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Hidrocortisona/farmacologia , Terapia de Imunossupressão , Imunossupressores/farmacologia , Rim/citologia , Camundongos , Camundongos Endogâmicos BALB C , Osteoblastos/citologia , Ratos , Ratos Wistar , Células Estromais/fisiologia , Transplante Heterólogo/fisiologia , Transplante Homólogo/fisiologia , Transplante Isogênico/fisiologiaRESUMO
The inflammatory reactions elicited in mice by subcutaneous injections of IFA and CFA had opposite effects when tested on local metacarpal shank bones and the distal epiphysis of shank bones. Although the intensity of the immune reactions was similar, IFA induced bone loss, while CFA induced bone formation, which was mostly periosteal in nature. BMC and BMD measurements were assessed by means of high resolution DEXA, using a hologic 4500A bone scanner with software dedicated for the analysis of small animal bones. DEXA scans were evaluated and related to histological and bone ash content analyses. The morphological and quantitative ash weight analyses of bones exposed to the adjuvants were consistent with DEXA bone density scan measurements.
Assuntos
Adjuvante de Freund , Lipídeos , Osteoartrite/induzido quimicamente , Osteoartrite/imunologia , Absorciometria de Fóton , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos , Osteoartrite/patologiaRESUMO
Heterotopic ossicles were induced in thigh muscles of immunosuppressed mice by implantation of suspension of several HeLa cell lines. These ossicles are the object of our research on osteoporosis. It was found that various HeLa cell lines differ in their potential to induce osteogenesis. In the previous paper we demonstrated the involvement of bone morphogenetic proteins (BMP-4 and BMP-6) secreted by HeLa cells in this phenomenon. In the present paper we try to find out the reason of the heterogeneity of various cell lines regarding the differences in their osteoinductive potencies. By the use of semiquantitative RT-PCR the differences in mRNA expression for several isoforms of BMP proteins in examined HeLa cell lines were found. The presence or absence of some of the BMP isoforms seems to be correlated with the quantity of heterotopically induced mineralised tissues. This was measured by weighing the deposited mineral after digestion of soft tissues surrounding the induced ossicles. This finding is supporting the thesis on high and uncontrolled heterogeneity of various HeLa cell lines used all over the world.
Assuntos
Proteínas Morfogenéticas Ósseas/genética , Expressão Gênica , Células HeLa/fisiologia , Família Multigênica , Osteogênese/fisiologia , Animais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Osteogênese/genética , Isoformas de Proteínas/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Osteogênese/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2 , Proteínas Morfogenéticas Ósseas/administração & dosagem , Tecido Conjuntivo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Camundongos , Músculo Esquelético/efeitos dos fármacos , Próteses e Implantes , Ratos , Fator de Crescimento Transformador beta/administração & dosagemRESUMO
Localized GvH reaction produced by the subcutaneous injection of parental lymphoid cells into the ear lobe of F1 recipient mice results in local activation of perichondrial chondrogenesis. Similarly, when the GvH reaction was elicited in shanks, the periosteal membranes at the site of immune reaction were stimulated to proliferate and to produce new bone. However, syngeneic lymphocytes activated in vivo by Con A and untreated syngeneic spleen and bone marrow cells administered locally produced similar response of bone and cartilage. Thus the lymphocytes activated either in the course of GvH reaction or syngeneic lymphocytes grafted into heterotopic sites presumably release mediators capable to stimulate periosteal/perichondrial membranes.
Assuntos
Condrogênese , Reação Enxerto-Hospedeiro , Osteogênese , Animais , Cartilagem da Orelha/cirurgia , Feminino , Transfusão de Linfócitos , Masculino , Camundongos , Periósteo/cirurgiaRESUMO
The authors present, in somewhat simplified form, a synthetic collection of information pertaining to fracture healing form the histological perspective. The mechanisms of fracture healing are described in reference to the histological construction of bone, phases in the healing process, the reactions taking place at the fracture site, and the mechanisms for regulating these processes with growth and discrimination factors.
RESUMO
Intradermal administration of concanavalin A, a potent T-cell mitogen, into an ear lap resulted in activation of chondrogenesis and stimulation of epidermis proliferation. This proliferation is sometimes invasive in character (pearls and epidermal nests form in the underlying connective tissue) but never turns into true cancerous lesions. This reaction can be delayed, but not prevented, by the prostaglandin inhibitor indomethacin. Stimulation of epidermis proliferation was also caused by administration of other immunomodulators, such as carrageenan type IV, Moloney sarcoma development, and rarely in the course of GvHr, but to much lesser degree than with concanavalin A. It is suggested that the same growth factors, which are mediators of local chondrocyte stimulation, are also mediators of keratinocyte activation.
Assuntos
Adjuvantes Imunológicos/toxicidade , Condrócitos/efeitos dos fármacos , Concanavalina A/toxicidade , Toxidermias/etiologia , Otopatias/induzido quimicamente , Orelha Externa/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Lesões Pré-Cancerosas/induzido quimicamente , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Transplante de Medula Óssea , Carragenina/toxicidade , Condrócitos/patologia , Toxidermias/patologia , Otopatias/patologia , Neoplasias da Orelha/etiologia , Neoplasias da Orelha/prevenção & controle , Orelha Externa/patologia , Epiderme/patologia , Epitélio/efeitos dos fármacos , Epitélio/patologia , Feminino , Reação Enxerto-Hospedeiro , Hiperplasia , Hipertrofia , Indometacina/uso terapêutico , Queratinócitos/patologia , Queratinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Camundongos Endogâmicos ICR , Camundongos SCID , Vírus do Sarcoma Murino de Moloney/patogenicidade , Lesões Pré-Cancerosas/patologia , Sarcoma Experimental/etiologia , Sarcoma Experimental/prevenção & controle , Transplante HeterotópicoRESUMO
Intravenous injection of a single dose of colchicine into inbred strains of BALB/c and CFW/L1 mice and into WAG rats did not effect rapid intramedullar bone formation and resorption, as has been claimed by the research group from Tokyo Medical and Dental University [14-17]. The applied doses of colchicine arrested metaphase during the first 4 hours postadministration and were noxious for hemopoietic tissue (necrosis of bone marrow was evident in 2 and 4 day specimens), but on longitudinal, serial sections of long bones there was no evidence of stimulation of osteogenesis at any point in time (2-26-day specimens). It is postulated that the system of ectopic osteogenesis by colchicine injection is not reproducible in mice and WAG rats, and the apparently osteogenic effect of colchicine, observed by the Ogura group [14-17], was mistakenly described as congenital osteopetrosis.
Assuntos
Medula Óssea/efeitos dos fármacos , Colchicina/farmacologia , Ossificação Heterotópica/induzido quimicamente , Animais , Feminino , Fêmur , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RatosAssuntos
Transplante Ósseo/métodos , Osteogênese , Animais , Técnica de Descalcificação , Procedimentos Cirúrgicos Dermatológicos , Modelos Animais de Doenças , Cães , Liofilização , Humanos , Camundongos , Camundongos Nus , Músculo Esquelético/patologia , Músculo Esquelético/cirurgia , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/patologia , Osteoblastos/patologia , Ratos , Pele/patologia , Células-Tronco/patologia , Preservação de Tecido , Transplante Heterólogo , Transplante HomólogoRESUMO
Small pieces (ca. 2-3 x 3-5 mm) of the urinary-tract mucosa from noninvasive papillary transitional-cell carcinomas of the bladder (ca. urotheliale papillare, n = 33), invasive transitional-cell carcinomas of the bladder (ca. urotheliale papillare infiltrans, n = 6, papillary transitional-cell carcinomas of the bladder with squamous metaplasia (ca. urotheliale papillare cum metaplasia planoepitheliale, n = 4), transitional-cell carcinomas in situ (ca. urotheliale in situ, n = 2), and squamous-cell carcinomas of the bladder (ca. planoepitheliale, n = 2) were grafted intramuscularly into cortisone-immunosuppressed mice to test the ability of transformed transitional epithelium to induce heterotopic osteogenesis. Altogether, 156 implants from 47 cases of urinary bladder carcinoma were performed. Histological examination of implants, excised 10-17 days later, revealed relatively good survival of the grafted epithelium, which had proliferated and, in some cases, formed cysts and islands but failed to induce heterotopic osteogenesis in the surrounding host tissues. In nine implants prepared from four cases (noninvasive papillary transitional-cell carcinoma of the bladder and invasive papillary transitional-cell carcinoma of the bladder, two cases each) a small amount of cartilage and/or bone was found in the stroma of grafted tissue. The rarity of this phenomenon--together with the observation that implants of normal human urinary-tract mucosa have never induced the formation of cartilage/bone, whereas in a similar system, dog or guinea-pig grafts are osteogenic--suggests that the cartilage/bone present in the stroma of implanted cancers is the result of metaplasia of the stroma of the neoplasm and not the product of any osteoinductive potency of human urothelium.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/patologia , Osteogênese , Neoplasias da Bexiga Urinária/patologia , Corticosteroides/administração & dosagem , Corticosteroides/farmacologia , Animais , Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células de Transição/fisiopatologia , Cães , Feminino , Cobaias , Humanos , Terapia de Imunossupressão , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos , Transplante de Neoplasias , Osteogênese/fisiologia , Neoplasias da Bexiga Urinária/fisiopatologiaRESUMO
In mice local or systemic administration of fluoride (5-25 mg NaF/kg body weight) during the proliferative phase of bone formation (up to 20 days) has no effect on the yield of bone formed either by local stimulation of periosteal membrane by Moloney sarcoma virus-induced tumour or on bone induced heterotopically by human KB cells. The lack of stimulatory activity of fluoride on rapidly induced osteogenesis in mice is in agreement with recent reports which show that fluoride is not a potent mitogen for human osteoblasts grown in vitro.