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1.
Am J Pathol ; 187(2): 292-303, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27939132

RESUMO

Neuronal protein 3.1 (P311), a conserved RNA-binding protein, represents the first documented protein known to stimulate transforming growth factor (TGF)-ß1 to -ß3 translation in vitro and in vivo. Because TGF-ßs play critical roles in fibrogenesis, we initiated efforts to define the role of P311 in skin scar formation. Here, we show that P311 is up-regulated in skin wounds and in normal and hypertrophic scars. Genetic ablation of p311 resulted in a significant decrease in skin scar collagen deposition. Lentiviral transfer of P311 corrected the deficits, whereas down-regulation of P311 levels by lentiviral RNA interference reproduced the deficits seen in P311-/- mice. The decrease in collagen deposition resulted in scars with reduced stiffness but also reduced scar tensile strength. In vitro studies using murine and human dermal fibroblasts showed that P311 stimulated TGF-ß1 to -ß3 translation, a process that involved eukaryotic translation initiation factor 3 subunit b as a P311 binding partner. This resulted in increased TGF-ß levels/activity and increased collagen production. In addition, P311 induced dermal fibroblast activation and proliferation. Finally, exogenous TGF-ß1 to -ß3, each restituted the normal scar phenotype. These studies demonstrate that P311 is required for the production of normal cutaneous scars and place P311 immediately up-stream of TGF-ßs in the process of fibrogenesis. Conditions that decrease P311 levels could result in less tensile scars, which could potentially lead to higher incidence of dehiscence after surgery.


Assuntos
Cicatriz/metabolismo , Cicatriz/patologia , Proteínas do Tecido Nervoso/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Resistência à Tração
2.
Lab Invest ; 94(2): 222-34, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24365748

RESUMO

In order to advance a culture model of human colonic neoplasia, we developed methods for the isolation and in vitro maintenance of intact colonic crypts from normal human colon tissue and adenomas. Crypts were maintained in three-dimensional Matrigel culture with a simple, serum-free, low Ca(2+) (0.15 mM) medium. Intact colonic crypts from normal human mucosa were viably maintained for 3-5 days with preservation of the in situ crypt-like architecture, presenting a distinct base and apex. Abnormal structures from adenoma tissue could be maintained through multiple passages (up to months), with expanding buds/tubules. Immunohistochemical markers for intestinal stem cells (Lgr5), growth (Ki67), differentiation (E-cadherin, cytokeratin 20 (CK20) and mucin 2 (MUC2)) and epithelial turnover (Bax, cleaved Caspase-3), paralleled the changes in function. The epithelial cells in normal crypts followed the physiological sequence of progression from proliferation to differentiation to dissolution in a spatially and temporally appropriate manner. Lgr5 expression was seen in a few basal cells of freshly isolated crypts, but was not detected after 1-3 days in culture. After 24 h in culture, crypts from normal colonic tissue continued to show strong Ki67 and MUC2 expression at the crypt base, with a gradual decrease over time such that by days 3-4 Ki67 was not expressed. The differentiation marker CK20 increased over the same period, eventually becoming intense throughout the whole crypt. In adenoma-derived structures, expression of markers for all stages of progression persisted for the entire time in culture. Lgr5 showed expression in a few select cells after months in culture. Ki67 and MUC2 were largely associated with the proliferative budding regions while CK20 was localized to the parent structure. This ex vivo culture model of normal and adenomatous crypts provides a readily accessible tool to help understand the growth and differentiation process in human colonic epithelium.


Assuntos
Adenoma/fisiopatologia , Biomarcadores/metabolismo , Colo/citologia , Neoplasias do Colo/fisiopatologia , Mucosa Intestinal/citologia , Modelos Biológicos , Técnicas de Cultura de Tecidos/métodos , Caderinas/metabolismo , Cálcio/metabolismo , Colágeno , Combinação de Medicamentos , Imunofluorescência , Humanos , Imuno-Histoquímica , Queratina-20/metabolismo , Antígeno Ki-67/metabolismo , Laminina , Microscopia Confocal , Mucina-2/metabolismo , Proteoglicanas , Receptores Acoplados a Proteínas G/metabolismo
3.
Heliyon ; 10(7): e28352, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38571657

RESUMO

The use of natural ester oils as electrically insulating fluids has gained significant attention from industries and electrical utilities as they aim to replace traditional mineral oils. However, most natural ester oils are derived from edible products, which has the potential to contribute to the food crisis. Therefore, nonedible green nanofluids made from cottonseed oil (CSO) have been targeted as a keen solution to this issue. However, Al2O3, TiO2, Fe2O3, SiO2, and graphene nanoparticles at (0.025, 0.05, and 0.075 wt/vol%) were used as additives, along with surfactant Olic Ac-id and Ethanol (1:5) due to their promising impact on the dielectric and thermal properties of the nanofluid. The nanofluid synthesis process was practically conducted in HV & Chemical Laboratories using one-step and two-step methods, and their breakdown voltage results and chemical properties (e.g., fire point, flash point, cloud point, pour point, viscosity, acidity, moisture content, resistivity, and dissipation factor) were compared. The physical mechanisms underlying these properties were also analyzed and tested. For the validation of the proposed vegetable oil the results have been compared with traditional mineral oil for high-voltage equipment's. The findings suggest that the proposed nonedible green nanofluids-based cottonseed oil (CSO) has a high potential to be used as electrically insulating fluids, providing a sustainable alternative to conventional mineral oils. Overall, this study provides insights into the use of non-edible green nanofluids as a solution to the potential contribution of natural ester oils to the food crisis. The findings highlight the importance of sustainable solutions in the energy industry and the need for further research in this area.

4.
J Immunol ; 185(7): 4354-62, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20833839

RESUMO

Psoriasis is a common immune-mediated disease in European populations; it is characterized by inflammation and altered epidermal differentiation leading to redness and scaling. T cells are thought to be the main driver, but there is also evidence for an epidermal contribution. In this article, we show that treatment of mouse skin overexpressing the IL-1 family member, IL-1F6, with phorbol ester leads to an inflammatory condition with macroscopic and histological similarities to human psoriasis. Inflammatory cytokines thought to be important in psoriasis, such as TNF-α, IL-17A, and IL-23, are upregulated in the mouse skin. These cytokines are induced by and can induce IL-1F6 and related IL-1 family cytokines. Inhibition of TNF or IL-23 inhibits the increased epidermal thickness, inflammation, and cytokine production. Blockade of IL-1F6 receptor also resolves the inflammatory changes in human psoriatic lesional skin transplanted onto immunodeficient mice. These data suggest a role for IL-1F family members in psoriasis.


Assuntos
Citocinas/imunologia , Psoríase/imunologia , Receptores de Interleucina-1/imunologia , Animais , Modelos Animais de Doenças , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Interleucina-1/imunologia , Interleucina-1/metabolismo , Subunidade alfa de Receptor de Interleucina-18/imunologia , Subunidade alfa de Receptor de Interleucina-18/metabolismo , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Camundongos Transgênicos , Reação em Cadeia da Polimerase , Psoríase/metabolismo , Psoríase/patologia , Receptores de Interleucina-1/metabolismo
5.
In Vitro Cell Dev Biol Anim ; 57(2): 174-190, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33403624

RESUMO

Organoid culture provides a powerful technology that can bridge the gap between monolayer cell culture on the one hand and whole animal or human subject research on the other. Tissues from many different organs from multiple species, including human, have already been successfully adapted to organoid growth. While optimal culture conditions have not yet been established for all tissue types, it seems that most tissues will, ultimately, be amenable to this type of culture. The colon is one of the tissues in which organoid culture was first established as a technology and which has been most successfully employed. The ready availability of histologically normal tissue as well as both premalignant and malignant tissue (often from the same individual) makes this possible. While individual tumors are highly variable relative to one another in organoid culture, a high degree of genotypic consistency exists between the tumor tissue and the histologically normal counterpart from a given source. Further, source material and tumor tissue in organoid culture demonstrate a high degree of genotypic consistency. Even after 6-9 mo in continuous culture, drift in the mutational profile has been shown to be minimal. Colon tissue maintained in organoid culture, thus, provides a good surrogate for the tissue of origin-a surrogate, however, that is as amenable to intervention with molecular, pharmacological, and immunological approaches as are more-traditionally studied cell lines.


Assuntos
Técnicas de Cultura de Células , Diferenciação Celular , Colo/citologia , Células Epiteliais/citologia , Técnicas de Cultura de Órgãos/métodos , Organoides/citologia , Sujeitos da Pesquisa , Animais , Colo/ultraestrutura , Humanos
6.
Calcif Tissue Int ; 86(4): 313-24, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20180099

RESUMO

The purpose of this study was to determine whether a mineral-rich extract derived from the red marine algae Lithothamnion calcareum could be used as a dietary supplement for prevention of bone mineral loss. Sixty C57BL/6 mice were divided into three groups based on diet: the first group received a high-fat Western-style diet (HFWD), the second group was fed the same HFWD along with the mineral-rich extract included as a dietary supplement, and the third group was used as a control and was fed a low-fat rodent chow diet (AIN76A). Mice were maintained on the respective diets for 15 months. Then, long bones (femora and tibiae) from both males and females were analyzed by three-dimensional micro-computed tomography (micro-CT) and (bones from female mice) concomitantly assessed in bone strength studies. Tartrate-resistant acid phosphatase (TRAP), osteocalcin, and N-terminal peptide of type I procollagen (PINP) were assessed in plasma samples obtained from female mice at the time of sacrifice. To summarize, female mice on the HFWD had reduced bone mineralization and reduced bone strength relative to female mice on the low-fat chow diet. The bone defects in female mice on the HFWD were overcome in the presence of the mineral-rich supplement. In fact, female mice receiving the mineral-rich supplement in the HFWD had better bone structure/function than did female mice on the low-fat chow diet. Female mice on the mineral-supplemented HFWD had higher plasma levels of TRAP than mice of the other groups. There were no differences in the other two markers. Male mice showed little diet-specific differences by micro-CT.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Osso e Ossos/efeitos dos fármacos , Extratos Celulares/farmacologia , Dieta , Rodófitas/química , Ração Animal , Animais , Osso e Ossos/química , Osso e Ossos/fisiologia , Osso e Ossos/ultraestrutura , Extratos Celulares/química , Dieta/veterinária , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Minerais/análise , Concentração Osmolar , Ocidente , Microtomografia por Raio-X
7.
J Ayub Med Coll Abbottabad ; 21(4): 31-3, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21067019

RESUMO

BACKGROUND: Pilonidal sinus disease has been treated for a long time with conventional open excision technique. The rhomboid flap of Limberg is a transposition flap that has been pleaded for treatment of this condition. METHODS: We present our experience with the Limberg technique for both primary and recurrent pilonidal sinuses. One hundred and ten patients, with pilonidal sinus disease were treated with rhombic excision and Limberg transposition flaps. All sinus tracts were resected en bloc, and the fasciocutaneous Limberg flap was prepared from the gluteal region and closed it with a suction drain. RESULTS: Full primary healing was obtained in 110 patients. 1 patient had minimal necrosis of flap and 2 had gaping of flap. Minor infection occurred in 3 patients. But all these complications healed uneventfully. The average hospital stay was 3 days. Follow up period was 1 year and 1 recurrence occurred. CONCLUSIONS: Limberg transposition flap is a promising surgical technique to treat pilonidal sinus.


Assuntos
Seio Pilonidal/cirurgia , Retalhos Cirúrgicos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Biomed Opt Express ; 10(2): 838-854, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30800518

RESUMO

We developed and applied rapid scanning laser-emission microscopy (LEM) to detect abnormal changes in cell nuclei for early diagnosis of cancer and cancer precursors. Regulation of chromatins is essential for genetic development and normal cell functions, while abnormal nuclear changes may lead to many diseases, in particular, cancer. The capability to detect abnormal changes in "apparently normal" tissues at a stage earlier than tumor development is critical for cancer prevention. Here we report using LEM to analyze colonic tissues from mice at-risk for colon cancer (induced by a high-fat diet) by detecting pre-polyp nuclear abnormality. By imaging the lasing emissions from chromatins, we discovered that, despite the absence of observable lesions, polyps, or tumors under stereoscope, high-fat mice exhibited significantly lower lasing thresholds than low-fat mice. The low lasing threshold is, in fact, very similar to that of adenomas and is caused by abnormal cell proliferation and chromatin deregulation that can potentially lead to cancer. Our findings suggest that conventional detection methods, such as colonoscopy followed by histopathology, by itself, may be insufficient to reveal hidden or early tumors under development. We envision that this innovative work will provide new insights into LEM and support existing tools for early tumor detection in clinical diagnosis, and fundamental biological and biomedical research of chromatin changes at the biomolecular level of cancer development.

9.
Arch Dermatol Res ; 300(1): 27-35, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17968574

RESUMO

Mice on a calorie-restricted (CR) diet (total calories restricted to 70% of ad libitum; AL) for periods of time ranging from 3 to 18 months were examined for response to topical treatment with all-trans retinoic acid (RA). Daily application of a 0.1% solution of RA to the shaved skin of UM-HET3 mice on an AL diet produced a severe irritation that was evident by day 4, maximal at day 7-8 and still detectable at day 14. Skin irritation was characterized by redness, dryness, flaking and failure of the hair to grow at the treated site. In CR mice, the same treatment produced little detectable irritation. Animals were sacrificed at the end of the retinoid-treatment period (day 7 or day 14) and skin from these animals was examined histologically. In both AL and CR mice, a similar degree of epidermal hyperplasia was observed. Numerous inflammatory cells (mononuclear cells and granulocytes) were present in the skin of both groups. Occasional S100-positive cells (presumably Langerhans cells) were also observed in the epidermis of skin from both groups. S100-positive cells were also observed in the dermis. When skin from CR and AL mice was incubated in organ culture for 3 days (on day 7 after initiation of RA treatment), similar levels of four different pro-inflammatory cytokines were found in the conditioned medium. Soluble type I collagen levels were also similar. In contrast, the level of matrix metalloproteinase-9 was lower in the conditioned medium of skin from CR mice than in conditioned medium from skin cultures of AL mice. Taken together, these studies suggest that CR may provide a way to mitigate the irritation that normally accompanies RA treatment without compromising the beneficial effects of retinoid use. CR appears to exert a protective effect at the target tissue level rather than by a reduction in pro-inflammatory events, per se.


Assuntos
Restrição Calórica , Dermatite Irritante/etiologia , Dermatite Irritante/prevenção & controle , Ceratolíticos/efeitos adversos , Tretinoína/efeitos adversos , Administração Tópica , Animais , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Colágeno Tipo I , Citocinas/metabolismo , Dermatite Irritante/patologia , Feminino , Ceratolíticos/administração & dosagem , Ceratolíticos/farmacologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos , Técnicas de Cultura de Órgãos , Proteínas S100/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Fatores de Tempo , Tretinoína/administração & dosagem , Tretinoína/farmacologia
10.
PLoS One ; 12(1): e0170136, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28068422

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0166178.].

11.
J Nutr Biochem ; 46: 90-99, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28486173

RESUMO

Dietary fish oils have potential for prevention of colon cancer, and yet the mechanisms of action in normal and tumor colon tissues are not well defined. Here we evaluated the impact of the colonic fatty acid milieu on the formation of prostaglandins and other eicosanoids. Distal tumors in rats were chemically induced to model inflammatory colonic carcinogenesis. After 21 weeks of feeding with either a fish oil diet containing an eicosapentaenoic acid/ω-6 fatty acid ratio of 0.4 or a Western fat diet, the relationships between colon fatty acids and prostaglandin E2 (PGE2) concentrations were evaluated. PGE2 is a key proinflammatory mediator in the colon tightly linked with the initiation and progression of colon cancer. The fish oil vs. the Western fat diet resulted in reduced total fatty acid concentrations in serum but not in colon. In the colon, the effects of the fish oil on fatty acids differed in normal and tumor tissue. There were distinct lipodomic patterns consistent with a lipogenic phenotype in tumors. In tumor tissue, the eicosapentaenoic acid/arachidonic acid ratio, cyclooxygenase-2 expression and the mole percent of saturated fatty acids were significant predictors of inter-animal variability in colon PGE2 after accounting for diet. In normal tissues from either control rats or carcinogen-treated rats, only diet was a significant predictor of colon PGE2. These results show that the fatty acid milieu can modulate the efficacy of dietary fish oils for colon cancer prevention, and this could extend to other preventive agents that function by reducing inflammatory stress.


Assuntos
Colo/metabolismo , Neoplasias do Colo/dietoterapia , Dinoprostona/metabolismo , Eicosanoides/metabolismo , Óleos de Peixe/farmacologia , Animais , Peso Corporal , Colo/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ciclo-Oxigenase 2/metabolismo , Suplementos Nutricionais , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos , Masculino , Ratos Endogâmicos F344
12.
Data Brief ; 13: 661-666, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28725670

RESUMO

Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate). The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1]).

13.
Diabetes ; 54(3): 855-61, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15734865

RESUMO

In the current study, rats were made diabetic with streptozotocin (STZ) and maintained for 8 weeks, during which time they were treated topically on alternative days with a solution of 0.1% all-trans retinoic acid in a vehicle of 70:30% ethanol/propylene glycol. STZ-induced diabetic rats treated with vehicle served as controls. Additional nondiabetic rats were treated with all-trans retinoic acid or vehicle in parallel. At the end of the 8-week period, rats from all four treatment groups were subjected to abrasion wound formation. Wounds healed more rapidly in vehicle-treated nondiabetic skin than in vehicle-treated diabetic skin (96% of the wound surface area closed in nondiabetic rats within 6 days vs. 41% closed in diabetic rats). Wounds in all-trans retinoic acid-treated diabetic skin healed more rapidly than wounds in vehicle-treated diabetic skin (85% of the wound surface area closed in all-trans retinoic acid-treated diabetic rats vs. 41% closed in vehicle-treated diabetic rats). At the histological level, recently healed skin from vehicle-treated diabetic rats was shown to contain a thin, wispy provisional matrix in which many of the embedded cells were rounded and some were pycnotic. In contrast, a much denser provisional matrix with large numbers of embedded spindle-shaped cells was observed in healed wounds from diabetic skin that had been pretreated with all-trans retinoic acid. The all-trans retinoic acid-treated diabetic skin was histologically similar to vehicle-treated (or all-trans retinoic acid-treated) skin from nondiabetic animals. In light of these findings, we suggest that prophylactic use of retinoid-containing preparations might be useful in preventing the development of nonhealing skin ulcers resultant from minor traumas in at-risk skin.


Assuntos
Diabetes Mellitus Experimental/complicações , Pele/lesões , Tretinoína/farmacologia , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Esquema de Medicação , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Tretinoína/administração & dosagem
14.
J Ethnopharmacol ; 103(3): 311-8, 2006 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-16221534

RESUMO

Pomegranate (Punica granatum) is an ancient fruit with exceptionally rich ethnomedical applications. The peel (pericarp) is well regarded for its astringent properties; the seeds for conferring invulnerability in combat and stimulating beauty and fertility. Here, aqueous fractions prepared from the fruit's peel and fermented juice and lipophilic fractions prepared from pomegranate seeds were examined for effects on human epidermal keratinocyte and human dermal fibroblast function. Pomegranate seed oil, but not aqueous extracts of fermented juice, peel or seed cake, was shown to stimulate keratinocyte proliferation in monolayer culture. In parallel, a mild thickening of the epidermis (without the loss of ordered differentiation) was observed in skin organ culture. The same pomegranate seed oil that stimulated keratinocyte proliferation was without effect on fibroblast function. In contrast, pomegranate peel extract (and to a lesser extent, both the fermented juice and seed cake extracts) stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 (MMP-1; interstitial collagenase) production by dermal fibroblasts, but had no growth-supporting effect on keratinocytes. These results suggest heuristic potential of pomegranate fractions for facilitating skin repair in a polar manner, namely aqueous extracts (especially of pomegranate peel) promoting regeneration of dermis, and pomegranate seed oil promoting regeneration of epidermis.


Assuntos
Cosméticos/farmacologia , Fibroblastos/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Lythraceae , Metaloproteinase 1 da Matriz/metabolismo , Extratos Vegetais/farmacologia , Pró-Colágeno/metabolismo , Proliferação de Células , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/metabolismo , Frutas , Humanos , Hiperplasia , Queratinócitos/metabolismo , Inibidores de Metaloproteinases de Matriz , Técnicas de Cultura de Órgãos , Sementes , Pele/efeitos dos fármacos , Pele/patologia
15.
Bone Rep ; 5: 141-149, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27350956

RESUMO

PURPOSE: Osteoporosis occurs in both women and men, but most of what we know about the condition comes from studies in females. The present study examined bone structure and function over an 18-month period in male C57BL/6 mice maintained on either a rodent chow diet (AIN76A) or a high-fat, Western-style diet (HFWD). Effects of mineral supplementation were assessed in both diets. METHODS: Trabecular and cortical bone structure in femora and vertebrae were assessed by micro-CT analysis. Following this, bone stiffness and strength measurements were made. Finally, bone levels of several cationic trace elements were quantified, and serum biomarkers of bone metabolism evaluated. RESULTS: Bone loss occurred over time in both diets but was more rapid and extensive in mice on the HFWD. Dietary mineral supplementation reduced bone loss in both diets and increased bone stiffness in the femora and bone stiffness and strength in the vertebrae. Bone content of strontium was increased in response to mineral supplementation in both diets. CONCLUSIONS: Bone loss was more severe in mice on the HFWD and mineral supplementation mitigated the effects of the HFWD. In comparison to previous findings with female C57BL/6 mice, the present studies indicate that males are more sensitive to diet and benefited from a healthy diet (AIN76A), while females lost as much bone on the healthy diet as on the HFWD. Male mice benefited from mineral supplementation, just as females did in the previous study.

16.
J Invest Dermatol ; 124(3): 524-9, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15737192

RESUMO

PADMA 28, a multi-component herbal mixture formulated according to an ancient Tibetan recipe, was assessed for effects on human dermal fibroblasts and epidermal keratinocytes in monolayer culture, and for effects on human skin in organ culture. PADMA 28 stimulated survival of fibroblasts in monolayer culture. In fibroblast monolayer culture and human skin organ culture, levels of matrix metalloproteinase-1 (MMP-1; interstitial collagenase) were reduced and type I procollagen production was increased. When keratinocytes were examined, there was no evidence of growth stimulation over a wide range of PADMA 28 concentrations. At high concentration, PADMA 28 inhibited keratinocyte proliferation. When organ cultures of human skin were treated with PADMA 28, there was no evidence of hyperplastic growth in the epidermis. Topical treatment of rhino mice with PADMA 28 failed to induce epidermal hyperplasia and was completely non-irritating. The ability to stimulate collagen production and inhibit the major collagen-degrading enzyme in skin without inducing a hyperplastic response in the epidermis may provide a basis for development of the herbal preparation as a "skin-repair" agent.


Assuntos
Derme/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Medicina Herbária , Extratos Vegetais/farmacologia , Adolescente , Adulto , Animais , Divisão Celular/efeitos dos fármacos , Derme/citologia , Células Epidérmicas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Camundongos , Camundongos Pelados , Técnicas de Cultura de Órgãos , Retinoides/fisiologia
17.
Arch Dermatol Res ; 297(2): 75-83, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15986218

RESUMO

The etiology of delayed or impaired wound-healing in diabetic individuals is multifactoral, but peripheral vascular dysfunction is an underlying factor in the majority of cases. Recent studies have shown that lipoic acid improves vascular function in diabetic skin and reduces the symptoms associated with the diabetic peripheral neuropathy. In this study, rats were made diabetic with streptozotocin (STZ) and treated systemically on alternative days with lipoic acid (100 mg/kg given via intraperitoneal injection) for 8 weeks. Untreated STZ-diabetic rats and non-diabetic rats served as control. At the end of the 8-week period, rats from all the three groups were subjected to abrasion wound formation. Skin wounds healed more rapidly in untreated non-diabetic rats than in the untreated diabetic rats. Wounds in lipoic acid-treated diabetic rats healed more rapidly than wounds in untreated diabetic rats. Subsequent in vitro studies demonstrated that lipoic acid protected endothelial cells from oxidant injury. At the same time, lipoic acid had no apparent effect on endothelial cell proliferation and had no measurable effect on fibroblast function (proliferation, collagen synthesis and matrix metalloproteinase expression). These findings suggest that prophylactic use of lipoic acid might be useful in preventing the development of non-healing skin ulcers from minor traumas in at-risk skin.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Ácido Tióctico/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Glicemia/análise , Peso Corporal , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Masculino , Estresse Oxidativo , Ratos , Pele/citologia , Estreptozocina , Ácido Tióctico/uso terapêutico
18.
Cancer Biol Ther ; 16(5): 724-32, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25799942

RESUMO

The oncofetal antigen - immature laminin receptor protein (OFA/iLRP) has been linked to metastatic tumor spread for several years. The present study, in which 2 highly-specific, high-affinity OFA/iLRP-reactive mouse monoclonal antibodies were examined for ability to suppress tumor cell growth and metastatic spread in the A20 B-cell leukemia model and the B16 melanoma model, provides the first direct evidence that targeting OFA/iLRP with exogenous antibodies can have therapeutic benefit. While the antibodies were modestly effective at preventing tumor growth at the primary injection site, both antibodies strongly suppressed end-organ tumor formation following intravenous tumor cell injection. Capacity of anti-OFA/iLRP antibodies to suppress tumor spread through the blood in the leukemia model suggests their use as a therapy for individuals with leukemic disease (either for patients in remission or even as part of an induction therapy). The results also suggest use against metastatic spread with solid tumors.


Assuntos
Antígenos de Neoplasias/imunologia , Melanoma Experimental/imunologia , Receptores de Laminina/imunologia , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Neoplasias/genética , Modelos Animais de Doenças , Melanoma Experimental/genética , Camundongos , Receptores de Laminina/genética
19.
Arch Dermatol Res ; 295(6): 255-62, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14564458

RESUMO

The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9- cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all- trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent.


Assuntos
Dermatite Irritante/patologia , Derme/patologia , Epiderme/patologia , Retinoides/farmacologia , Tretinoína/análogos & derivados , Alitretinoína , Animais , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Camundongos , Camundongos Pelados , Retinoides/química , Tretinoína/química , Tretinoína/farmacologia
20.
J Coll Physicians Surg Pak ; 23(1): 37-41, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23286621

RESUMO

OBJECTIVE: To determine the effectiveness of students' rating as a teacher evaluation tool. STUDY DESIGN: Concurrent mixed method. PLACE AND DURATION OF STUDY: King Edward Medical University, Lahore, from January to June 2010. METHODOLOGY: Anonymous 5-point Likert scale survey questionnaire was conducted involving a single class consisting of 310 students and 12 students were selected for structured interview based on non-probability purposive sampling. Informed consent was procured. They were required to rate 6 teachers and were supposed to discuss teachers' performance in detail. Quantitative data collected through survey was analyzed using SPSS 15 and qualitative data was analyzed with the help of content analysis by identifying themes and patterns from thick descriptions. This student feedback would show the effectiveness in terms of its feasibility and as an indicator of teaching attributes. RESULTS: Descriptive statistics of quantitative data obtained from survey was used to calculate mean and standard deviation for all teachers' individually. This showed the average direction of the student ratings. Percentages of the responses calculated of teacher A were 85.96%, teacher B 65.53, teacher C 65.20%, teacher D 69.62%, teacher E 65.32% and teacher F 64.24% in terms of overall effectiveness of their teaching. Structured interviews generated qualitative data which validated the students' views about strengths and weaknesses of teachers, and helped to determine the effectiveness of their rating and feedback. CONCLUSION: This simple rating system clearly showed its importance and hence can be used in institutions as a regular evaluating method of teaching faculty.


Assuntos
Docentes de Medicina/normas , Retroalimentação , Estudantes de Medicina , Ensino/normas , Adulto , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Paquistão , Reprodutibilidade dos Testes , Estatística como Assunto , Inquéritos e Questionários , Ensino/métodos , Adulto Jovem
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