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The aim of this study was to compare quilting suture with axillary drain versus conventional sutures with axillary and pectoral drain on the formation of seroma after modified radical mastectomy with axillary lymph node dissection. The study was undertaken among 90 female patients with breast cancer who were candidates for modified radical mastectomy with axillary clearance. The intervention group (N = 43) with quilting and axillary drain placement and the control group (N = 33) without quilting with axillary and pectoral drain placement. All the patients were followed up for complications pertaining to this procedure. There were no significant differences between the two groups with regard to demographic characteristics, comorbidities, pre-operative chemotherapy, post-operative pathological findings, lymph node involvement or clinical staging. The incidence of seroma formation on follow-up was significantly lower in the intervention group than that in the control group (23% versus 58%; p < 0.05) whereas there was no significant difference with respect to flap necrosis, superficial skin necrosis and wound gaping between the two groups. Furthermore, it took a shorter duration for seroma to resolve in the intervention group (4 days versus 9 days; p < 0.001) with a smaller duration of hospital stay (4 days versus 9 days; p < 0.001). The use of quilting sutures for flap fixation in order to obliterate dead space post-modified radical mastectomy with placement of axillary drain significantly reduced seroma formation along with shorter duration of wound drainage and a smaller hospital stay with only slightly increased operative time. Therefore, we recommend quilting of flap as a routine step after mastectomy.
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With the COVID-19 outbreak, many challenges are posed before the scientific world to curb this pandemic. The diagnostic testing, treatment, and vaccine development for this infection caught the scientific community's immediate attention. Currently, despite the global proliferation of COVID-19 vaccination, the specific treatment for this disease is yet unknown. Meanwhile, COVID-19 detection or diagnosis using polymerase chain reaction (PCR)-based me hods is expensive and less reliable. Moreover, this technique needs much time to furnish the results. Thus, the elaboration of a highly sensitive and fast method of COVID-19 diagnostics is of great importance. The spectroscopic approach is herein suggested as an efficient detection methodology for COVID-19 diagnosis, particularly Raman spectroscopy, infrared spectroscopy, and mass spectrometry.
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We investigate room temperature core level and valence band spectra of BaBiO3 using x-ray photoemission spectroscopy and band structure calculations. The features in the valence band spectrum were studied using density functional theory (DFT) under local density approximation (LDA) and Tran Blaha modified Becke Johnson (TB mBJ) exchange potential. The calculations were performed for three different structural parameters; monoclinic, cubic and monoclinic (M[Formula: see text]). Our results of the core level spectrum and DFT calculations rule out charge disproportionation of the Bi ions. The valence band spectrum displays gap at the Fermi edge and fine structures in the region close to the Fermi edge. The DFT calculation under TB mBJ for the monoclinic structure is able to generate gap and match the energy positions of the fine structure in a better way. Our calculation results show that there are holes in the O 2[Formula: see text] states and unequal transfer of electrons to the states of the Bi ions. Such mechanism could lead to bond disproportionation and its association with the fine structures in the valence band. The current results reveal the significance of strong link between the lattice distortion and electronic structure and hence to its physical properties.
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Photodynamic therapy (PDT) is a treatment that uses photosensitizing agents to kill cancer cells. Scientific community has been eager for decades to design an efficient PDT drug. Under such purview, the current report deals with the computational photodynamic behavior of ruthenium(II) nitrosyl complex containing N, N'-salicyldehyde-ethylenediimine (SalenH2), the synthesis and X-ray crystallography of which is already known [Ref. 38,39]. Gaussian 09W software package was employed to carry out the density functional (DFT) studies. DFT calculations with Becke-3-Lee-Yang-Parr (B3LYP)/Los Alamos National Laboratory 2 Double Z (LanL2DZ) specified for Ru atom and B3LYP/6-31G(d,p) combination for all other atoms were used using effective core potential method. Both, the ground and excited states of the complex were evolved. Some known photosensitizers were compared with the target complex. Pthalocyanine and porphyrin derivatives were the compounds selected for the respective comparative study. It is suggested that effective photoactivity was found due to the presence of ruthenium core in the model complex. In addition to the evaluation of theoretical aspects in vitro anticancer aspects against COLO-205 human cancer cells have also been carried out with regard to the complex. More emphasis was laid to extrapolate DFT to depict the chemical power of the target compound to release nitric oxide. A promising visible light triggered nitric oxide releasing power of the compound has been inferred. In vitro antiproliferative studies of [RuCl3(PPh3)3] and [Ru(NO)(Salen)(Cl)] have revealed the model complex as an excellent anticancer agent. From IC50 values of 40.031mg/mL in former and of 9.74mg/mL in latter, it is established that latter bears more anticancer potentiality. From overall study the DFT based structural elucidation and the efficiency of NO, Ru and Salen co-ligands has shown promising drug delivery property and a good candidacy for both chemotherapy as well as light therapy.
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Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Compuestos de Rutenio/farmacología , Línea Celular Tumoral , Computadores Moleculares , HumanosRESUMEN
AIM AND OBJECTIVES: To analyze the relationship between subjective and objective evaluations of pre-treatment posed smiles in patients with facial asymmetry and to assess the influence of dentofacial structures involved in asymmetry on the perception of smile attractiveness. SAMPLE: Thirty-five patients (25 males and 10 females) between 18 and 25 years of age with facial asymmetry were selected. MATERIALS AND METHODS: Pre-treatment clinical photographs of posed smiles were subjectively evaluated by a panel of 20 orthodontists, 20 oral surgeons, and 20 laypersons. A customized Smile Mesh program was used for objective evaluation of the same smiles. Direct comparison among three smile groups (unattractive, slightly attractive, and attractive) for different Smile Mesh measurements was carried out using two-way anova test. Additionally, linear regression was performed to evaluate whether these measurements could predict the attractiveness of captured smiles. RESULTS: Patients with 'slightly attractive' smiles had a significantly greater distance between the incisal margin of the maxillary central incisor and the lower lip during smiling. The Smile Index was significantly greater in attractive smiles. However, based on the coefficients of linear regression, no objectively gathered measurement could predict smile attractiveness. CONCLUSIONS: Attractiveness or unattractiveness of smiles in patients with facial asymmetry could not be predicted by any measurement of Smile Mesh. The presence of facial asymmetry did not significantly influence the perception of smile esthetics.
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Estética Dental , Asimetría Facial/psicología , Sonrisa , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Percepción , Adulto JovenRESUMEN
Despite the existence of chemotherapy, there is no effective cure for leishmaniasis. In the light of recommended therapeutic regimen is attributed for toxicity and development of clinical resistance, exploration of an efficient method of drug delivery could be one of the option in reducing the dosage and toxicity of drugs. This work is aimed in such fashion to study the enhanced antileishmanial activity of miltefosine with silver-nanoparticles (AgNPs) synthesized by using Anethum graveolens (dill) leaf extract as reducing agent. AgNPs were synthesized in a single step process and characterized by UV-visible, X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FTIR) to understand the crystal structure and functional groups on their surface. TEM analysis showed that the synthesized AgNPs are of an average size of 35 nm. By performing MTT assay, we found that, AgNPs (between 20 and 100 µM) are biocompatible in nature through pertaining >80% viability of macrophages. Furthermore, AgNPs alone (50 µM) have not shown antileishmanial effect on promastigote stage of Leishmania parasite but in combination with miltefosine (12.5 µM and 25 µM), it magnifies the leishmanicidal effect of miltefosine by â¼2-folds (i.e. AgNPs cut down the IC50 of miltefosine about to half). Scanning electron microscopic (SEM) observation for morphological aberration and genomic DNA fragmentation in promastigotes confirmed the enhanced effect of meltefosine in combination with AgNPs (50 µM AgNPs plus 12.5 µM miltefosine). Similarly, this combination has likely shown a slight augmentation (p = 0.057) of miltefosine (2.5 µM) leishmanicidal efficacy on amastigote stage of the parasite in infected human macrophages by reducing their intracellular growth.
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Anethum graveolens/química , Antiprotozoarios/farmacología , Leishmania/efectos de los fármacos , Nanopartículas del Metal/ultraestructura , Fosforilcolina/análogos & derivados , Extractos Vegetales/administración & dosificación , Animales , Materiales Biocompatibles/química , Línea Celular Tumoral , Roturas del ADN/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Leishmania/genética , Macrófagos/parasitología , Nanopartículas del Metal/química , Ratones , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Fosforilcolina/farmacología , Hojas de la Planta/química , Plata , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent with cancer cell-selective cell death inducing effect. However, the major limitation in the usage of TRAIL as a chemotherapeutic agent is the development of TRAIL resistance in many cancer types including myeloid leukemia. In this study, we report for the first time that Medicarpin (Med), a naturally occurring phytoalexin sensitizes myeloid leukemia cells to TRAIL-induced apoptosis. Combination of Med and TRAIL induced significantly higher apoptosis compared with that of the individual treatments of either agent alone through activation of both the extrinsic and the intrinsic cell death pathways characterized by the activation of caspases 8, 9, 3, and 7. Med treatment downregulated antiapoptotic proteins (Survivin, Bcl2, Bcl-xL, XIAP, and c-FLIP), upregulated pro-apoptotic proteins (Bax, Cytochrome C, Smac/Diablo, Bid, truncated Bid (tBid), p-eIF2α, Bip, and CHOP (CCAAT-enhancer binding protein homologous protein)), induced G2/M cell-cycle arrest, and increased the expression of the functional TRAIL receptor DR5 through activation of the ROS-JNK-CHOP pathway. Gain and loss of function studies clearly indicated that DR5 expression was critical for Med-induced TRAIL sensitization. The Med-induced TRAIL sensitization did not involve the NFkB signaling pathway or redistribution of DR5 in lipid rafts. The concomitant treatment with Med and TRAIL showed robust apoptotic effects in primary myeloid leukemia cells but had no toxic effects in primary human peripheral blood mononuclear cells (PBMCs). In conclusion, our results suggest that Med sensitizes myeloid leukemia cells to TRAIL-induced apoptosis through the upregulation of DR5 through activation of the ROS-JNK-CHOP pathway.
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Apoptosis/efectos de los fármacos , Fabaceae/química , Leucemia Mieloide/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Pterocarpanos/farmacología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Sesquiterpenos/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Pterocarpanos/química , Especies Reactivas de Oxígeno/metabolismo , Sesquiterpenos/química , Factor de Transcripción CHOP/metabolismo , FitoalexinasRESUMEN
Recently, we reported that extract of Dalbergia sissoo made from leaves and pods have antiresorptive and bone-forming effects. The positive skeletal effect attributed because of active molecules present in the extract of Dalbergia sissoo. Caviunin 7-O-[ß-D-apiofuranosyl-(1-6)-ß-D-glucopyranoside] (CAFG), a novel isoflavonoid show higher percentage present in the extract. Here, we show the osteogenic potential of CAFG as an alternative for anabolic therapy for the treatment of osteoporosis by stimulating bone morphogenetic protein 2 (BMP2) and Wnt/ß-catenin mechanism. CAFG supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur and decreased bone turnover markers better than genistein. Oral administration of CAFG to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased the expression of osteogenic genes in femur and show new bone formation without uterine hyperplasia. CAFG increased mRNA expression of osteoprotegerin in bone and inhibited osteoclast activation by inhibiting the expression of skeletal osteoclastogenic genes. CAFG is also an effective accelerant for chondrogenesis and has stimulatory effect on the repair of cortical bone after drill-hole injury at the tissue, cell and gene level in mouse femur. At cellular levels, CAFG stimulated osteoblast proliferation, survival and differentiation. Signal transduction inhibitors in osteoblast demonstrated involvement of p-38 mitogen-activated protein kinase pathway stimulated by BMP2 to initiate Wnt/ß-catenin signaling to reduce phosphorylation of GSK3-ß and subsequent nuclear accumulation of ß-catenin. Osteogenic effects were abrogated by Dkk1, Wnt-receptor blocker and FH535, inhibitor of TCF-complex by reduction in ß-catenin levels. CAFG modulated MSC responsiveness to BMP2, which promoted osteoblast differentiation via Wnt/ß-catenin mechanism. CAFG at 1 mg/kg(/)day dose in ovariectomy mice (human dose â¼0.081 mg/kg) led to enhanced bone formation, reduced bone resorption and bone turnover better than well-known phytoestrogen genistein. Owing to CAFG's inherent properties for bone, it could be positioned as a potential drug, food supplement, for postmenopausal osteoporosis and fracture repair.
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Enfermedades Óseas Metabólicas/tratamiento farmacológico , Células de la Médula Ósea/efectos de los fármacos , Proteína Morfogenética Ósea 2/metabolismo , Huesos/efectos de los fármacos , Glicósidos/farmacología , Isoflavonas/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo , Animales , Animales Recién Nacidos , Enfermedades Óseas Metabólicas/genética , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/patología , Enfermedades Óseas Metabólicas/fisiopatología , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Proteína Morfogenética Ósea 2/genética , Huesos/metabolismo , Huesos/patología , Huesos/fisiopatología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Condrogénesis/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica , Genisteína/farmacología , Células HEK293 , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Ratones Endogámicos BALB C , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoblastos/patología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Ovariectomía , Factores de Tiempo , Transfección , Vía de Señalización Wnt/genética , beta Catenina/genéticaRESUMEN
MicroRNAs (miRNAs) are short non-coding RNAs that interfere with translation of specific target mRNAs and thereby regulate diverse biological processes. Recent studies have suggested that miRNAs might have a role in osteoblast differentiation and bone formation. Here, we show that miR-542-3p, a well-characterized tumor suppressor whose downregulation is tightly associated with tumor progression via C-src-related oncogenic pathways, inhibits osteoblast proliferation and differentiation. miRNA array profiling in Medicarpin (a pterocarpan with proven bone-forming effects) induced mice calvarial osteoblast cells and further validation by quantitative real-time PCR revealed that miR-542-3p was downregulated during osteoblast differentiation. Over-expression of miR-542-3p inhibited osteoblast differentiation, whereas inhibition of miR-542-3p function by anti-miR-542-3p promoted expression of osteoblast-specific genes, alkaline phosphatase activity and matrix mineralization. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified BMP-7 (bone morphogenetic protein 7) as a direct target of miR-542-3p. It was seen that over-expression of miR-542-3p leads to repression of BMP-7 and inhibition of BMP-7/PI3K- survivin signaling. This strongly suggests that miR-542-3p suppresses osteogenic differentiation and promotes osteoblast apoptosis by repressing BMP-7 and its downstream signaling. Furthermore, silencing of miR-542-3p led to increased bone formation, bone strength and improved trabecular microarchitecture in sham and ovariectomized (Ovx) mice. Although miR-542-3p is known to be a tumor repressor, we have identified second complementary function of miR-542-3p where it inhibits BMP-7-mediated osteogenesis. Our findings suggest that pharmacological inhibition of miR-542-3p by anti-miR-542-3p could represent a therapeutic strategy for enhancing bone formation in vivo.
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Proteína Morfogenética Ósea 7/genética , Diferenciación Celular , Proliferación Celular , MicroARNs/genética , MicroARNs/metabolismo , Osteoblastos/citología , Osteogénesis , Animales , Proteína Morfogenética Ósea 7/metabolismo , Células Cultivadas , Regulación hacia Abajo , Femenino , Regulación del Desarrollo de la Expresión Génica , Ratones , Ratones Endogámicos BALB C , Osteoblastos/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: The aim of this study was to evaluate and compare the cephalometric measurements obtained from computerized tracing of direct digital radiographs and hand tracing of their digital radiographic printouts. MATERIAL AND METHODS: The soft- and hard-copies of pre-treatment lateral cephalograms of 40 subjects (both males and females) within the age group of 10-30 years, irrespective of the type of malocclusion were taken. Total 26 measurements (13 linear and 13 angular) were obtained using both the manual and the digital technique. RESULTS: Amongst the linear measurements, Anterior facial height (AFH), Posterior facial height (PFH), Upper lip length (ULL), Lower lip length (LLL), Anterior cranial base length (ACBL), Posterior cranial base length (PCBL), Maxillary length (MxL), Mandibular length (MdL), Lower incisor to NB line (L1 to NB) and Lower lip protrusion (LLP) showed statistically significant difference between the two techniques but were clinically acceptable (difference between the digital and manual technique were less than 2 units (1 unit = 1 mm for linear measurements and 1° for angular measurements). While amongst the angular measurements, only occlusal plane angle showed statistically significant difference between the two techniques that was not clinically acceptable. CONCLUSION: Digital measurements obtained from monitor-displayed images (soft copy) were found to be reproducible and comparable to the manual method done on its hard copy, for all the measurements except occlusal plane angle (SN-occlusal plane).
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OBJECTIVE: To evaluate the amount of canine retraction with periodontal distraction using miniscrew implants and NiTi coil spring. MATERIAL AND METHOD: Sample comprised of 25 patients who were scheduled for all 1st premolar extraction (13 males and 12 females), in the age range of 16-22 years with mean age 18.8 ± 2.7 years. For each patient left side served as control side (Group I) and right side as experimental side (Group II). At the time of first premolar extraction, periodontal distraction was performed only on the experimental side, followed by retraction of canine from mini-implant by closed NiTi coil spring on both the sides. "Nemotech" software was used to evaluate the amount of canine retraction for a period of 3 months. RESULTS: Significantly higher amount of tooth movement was seen from T0-T1 and from T1-T2 in Group II for the maxillary parameters 3C-5C, 6CF-3C, 3C-I/3C-J and for the mandibular parameter 6CFâ³-3Câ³. Whereas no significant amount of tooth movement was observed for maxillary and mandibular parameters between T2-T3 except for 6CFâ³-3Câ³ (p ≤ 0.01) which was significantly higher for the Group II. CONCLUSION: There was accelerated canine retraction on the periodontal distraction side as compared to the control side, with negligible anchorage loss.
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PURPOSE: 6-C-ß-D-glucopyranosyl-(2S,3S)-(+)-5,7,3',4'-tetrahydroxydihydroflavonol (GTDF) is a novel compound isolated from Ulmus wallichiana, reported to have bone anabolic action in ovariectomized rats. Here, we studied the effect of GTDF in glucocorticoid (GC)-induced bone loss and its mode of action. METHODS: Osteoblasts were cultured from rat calvaria or bone marrow to study apoptosis and differentiation by dexamethasone (Dex), methylprednisolone (MP), GTDF, quercetin and rutin. Female Sprague Dawley rats were treated with Dex or MP with or without GTDF or PTH. Efficacy was evaluated by bone microarchitecture using microcomputed tomography, determination of new bone formation by fluorescent labeling of bone and osteoblast apoptosis by co-labeling bone sections with Runx-2 and TUNEL. Serum osteocalcin was determined by ELISA. RESULTS: GTDF preserved trabecular and cortical bones in the presence of Dex and MP and mitigated the MP-mediated suppression of serum osteocalcin. Co-administration of GTDF to MP rats increased mineral apposition, bone formation rates, bone biomechanical strength, reduced osteoblast apoptosis and increased osteogenic differentiation of bone marrow stromal cells compared to MP group, suggesting in vivo osteogenic effect of GTDF. These effects of GTDF were to a great extent comparable to PTH. GTDF prevented GC-induced osteoblast apoptosis by inhibiting p53 expression and acetylation, and activation of AKT but did not influence transactivation of GC receptor (GR). CONCLUSIONS: GTDF protects against GC-induced bone loss by promoting osteoblast survival through p53 inhibition and activation of AKT pathways but not as a GR antagonist. GTDF has the potential in the management of GC-induced osteopenia.
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Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Flavonoles/uso terapéutico , Glucocorticoides/efectos adversos , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis/prevención & control , Ulmus/química , Animales , Apoptosis/efectos de los fármacos , Fenómenos Biomecánicos , Huesos/metabolismo , Femenino , Flavonoles/aislamiento & purificación , Flavonoles/farmacología , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Glucósidos/uso terapéutico , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Osteocalcina/sangre , Osteoporosis/sangre , Osteoporosis/inducido químicamente , Hormona Paratiroidea/metabolismo , Hormona Paratiroidea/farmacología , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
PURPOSE: Daidzein (Daid) has been implicated in bone health for its estrogen-'like' effects but low bioavailability, unfavorable metabolism and uterine estrogenicity impede its clinical potential. This study was aimed at assessing isoformononetin (Isoformo), a naturally occurring methoxydaidzein, for bone anabolic effect by overcoming the pitfalls associated with Daid. METHODS: Sprague-Dawley ovariectomized (OVx) rats with established osteopenia were administered Isoformo, 17ß-oestradiol (E2) or human parathyroid hormone. Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labeling of bone. Osteoblast apoptosis was measured by co-labeling of bone sections with Runx-2 and TUNEL. Biochemical markers of bone metabolism were measured by ELISA. Plasma and bone marrow levels of Isoformo and Daid were determined by LC-MS-MS. Rat bone marrow stromal cells were harvested to study osteoblastic differentiation by Isoformo and Daid. New born rat pups were injected with Isoformo and Daid to study the effect of the compounds on the expression of osteogenic genes in the calvaria by real time PCR. RESULTS: In osteopenic rats, Isoformo treatment restored trabecular microarchitecture, increased new bone formation, increased the serum osteogenic marker (procollagen N-terminal propeptide), decreased resorptive marker (urinary C-terminal teleopeptide of type I collagen) and diminished osteoblast apoptosis in bone. At the most effective osteogenic dose of Isoformo, plasma and bone marrow levels were comprised of ~90% Isoformo and the rest, Daid. Isoformo at the concentration reaching the bone marrow achieved out of its most effective oral dosing induced stromal cell mineralization and osteogenic gene expression in the calvaria of neonatal rats. Isoformo exhibited uterine safety. CONCLUSIONS: Our study demonstrates that Isoformo reverses established osteopenia in adult OVx rats likely via its pro-survival effect on osteoblasts. Given its bone anabolic and anti-catabolic effects accompanied with safety at uterine level we propose its potential in the management of postmenopausal osteoporosis.
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Enfermedades Óseas Metabólicas/tratamiento farmacológico , Huesos/efectos de los fármacos , Isoflavonas/uso terapéutico , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis/prevención & control , Fitoterapia , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/sangre , Biomarcadores/orina , Conservadores de la Densidad Ósea/metabolismo , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Resorción Ósea/prevención & control , Calcificación Fisiológica/efectos de los fármacos , Femenino , Isoflavonas/metabolismo , Isoflavonas/farmacología , Metabolismo/efectos de los fármacos , Osteogénesis/genética , Osteoporosis/etiología , Osteoporosis/metabolismo , Ovariectomía , Fitoestrógenos/metabolismo , Fitoestrógenos/farmacología , Fitoestrógenos/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Sprague-Dawley , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Útero/efectos de los fármacosRESUMEN
UNLABELLED: Effects of cladrin treatment and withdrawal in osteopenic rats were studied. Cladrin improved trabecular microarchitecture, increased lumbar vertebral compressive strength, augmented coupled remodeling, and increased bone osteogenic genes. A significant skeletal gain was maintained 4 weeks after cladrin withdrawal. Findings suggest that cladrin has significant positive skeletal effects. INTRODUCTION: We showed that a standardized extract of Butea monosperma preserved trabecular bone mass in ovariectomized (OVx) rats. Cladrin, the most abundant bioactive compound of the extract, promoted peak bone mass achievement in growing rats by stimulating osteoblast function. Here, we studied the effects of cladrin treatment and withdrawal on the osteopenic bones. METHODS: Adult female Sprague-Dawley rats were OVx and left untreated for 12 weeks to allow for significant estrogen deficiency-induced bone loss, at which point cladrin (1 and 10 mg/kg/day) was administered orally for another 12 weeks. Half of the rats were killed at the end of the treatments and the other half at 4 weeks after treatment withdrawal. Sham-operated rats and OVx rats treated with PTH or 17ß-estradiol (E2) served as various controls. Efficacy was evaluated by bone microarchitecture using microcomputed tomographic analysis and fluorescent labeling of bone. qPCR and western blotting measured mRNA and protein levels in bone and uterus. Specific ELISA was used for measuring levels of serum PINP and urinary CTx. RESULTS: In osteopenic rats, cladrin treatment dose dependently improved trabecular microarchitecture, increased lumbar vertebral compression strength, bone formation rate (BFR), cortical thickness (Cs.Th), serum PINP levels, and expression of osteogenic genes in bones; and reduced expression of bone osteoclastogenic genes and urinary CTx levels. Cladrin had no uterine estrogenicity. Cladrin at 10 mg/kg maintained acquired skeletal gains 4 weeks after withdrawal. CONCLUSION: Cladrin had positive skeletal effects in osteopenic rats that were maintained after treatment withdrawal.
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Conservadores de la Densidad Ósea/uso terapéutico , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Isoflavonas/uso terapéutico , Animales , Biomarcadores/sangre , Peso Corporal/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/farmacología , Enfermedades Óseas Metabólicas/fisiopatología , Fuerza Compresiva/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Evaluación Preclínica de Medicamentos/métodos , Femenino , Fémur/efectos de los fármacos , Fémur/metabolismo , Fémur/fisiopatología , Regulación de la Expresión Génica/efectos de los fármacos , Isoflavonas/administración & dosificación , Isoflavonas/farmacología , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/fisiopatología , Tamaño de los Órganos/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Ovariectomía , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Tibia/efectos de los fármacos , Tibia/fisiopatología , Útero/efectos de los fármacos , Útero/patología , Microtomografía por Rayos XRESUMEN
Increased hepatic glucose output is one of the major causes of fasting hyperglycemia in diabetic patients. In this study, we investigated the mechanism of action of coagulanolide on hepatic glucose, regulating enzymes in type 2 diabetic C57BL/KsJ-db/db (db/db) mice. Coagulanolide is an active component of Withania coagulans fruit. Oral administration of coagulanolide for 3 weeks decreases fasting blood glucose and plasma insulin significantly, and it improves glucose tolerance in the db/db mice group. The enzyme activity and protein expression of glucokinase and pyruvate kinase was significantly enhanced in coagulanolide-treated db/db group when compared with untreated one. On the other hand, activities and protein expression of fructose-1,6-bisphosphatase, glucose 6-phosphatase, phosphoenolpyruvate carboxykinase, and glycogen phosphorylase enzymes were significantly lowered in treated group. The treatment with coagulanolide also normalizes the concentrations of plasma cholesterol, triglyceride, free fatty acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the db/db mice. These findings suggested that the coagulanolide is useful in the control of fasting hyperglycemia in type 2 diabetes by regulating the production of hepatic glucose.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hígado/efectos de los fármacos , Witanólidos/farmacología , Administración Oral , Animales , Glucemia/metabolismo , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Modelos Animales de Enfermedad , Enzimas/metabolismo , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/administración & dosificación , Insulina/sangre , Lípidos/sangre , Hígado/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Factores de Tiempo , Witanólidos/administración & dosificaciónRESUMEN
PURPOSE: This study was designed to evaluate the buccal corridor in smile esthetics and to correlate it with underlying hard tissues. MATERIALS AND METHODS: Posed smiling frontal photographs, digital posterior-anterior (PA) cephalograms, and study models of 25 males and 25 females in age range of 18-25 years were taken. Photographs were evaluated for smile esthetics by eight orthodontists, eight plastic surgeons, eight beauticians and eight lay people to group them into three groups with least attractive, average and attractive smile and buccal corridor width was measured. Digital PA cephalograms were transferred on Nemo-tech software for frontal facial analysis. Intercanine and intermolar widths were measured on upper study model with the help of a digital calliper. RESULTS: The buccal corridor width was least in attractive smile group and maximum in least attractive smile group. The buccal corridor width had a negligible correlation with hard tissues and a mild to moderate inverse correlation with intercanine and intermolar widths within the groups. CONCLUSION: As the amount of buccal corridor display was increased, smiling images were scored less attractive by the evaluators. The buccal corridor is not influenced by underlying skeletal hard tissues but have mild to moderate inverse correlation with the intercanine and intermolar width.
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Mejilla/anatomía & histología , Estética Dental , Labio/anatomía & histología , Sonrisa , Adolescente , Adulto , Puntos Anatómicos de Referencia/anatomía & histología , Actitud , Actitud del Personal de Salud , Industria de la Belleza , Cefalometría/métodos , Mentón/anatomía & histología , Diente Canino/anatomía & histología , Arco Dental/anatomía & histología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Mandíbula/anatomía & histología , Maxilar/anatomía & histología , Modelos Dentales , Diente Molar/anatomía & histología , Ortodoncia , Fotograbar , Radiografía Dental Digital/métodos , Cirugía Plástica , Adulto Joven , Cigoma/anatomía & histologíaRESUMEN
Wohlfahrtia magnifica larvae cause myiasis in mammals, mainly in sheep and rarely in human. In human it may infest the ear, eye, mouth or nose, damaging living tissues. We report a case of ocular myiasis in 1.5 years old child belonging to urban slum after history of minor injury on left upper lid due to fall from bed. The purpose of reporting this case is to highlight the ocular association of W. magnifica.
RESUMEN
UNLABELLED: Presently the relationship between CD28, biological marker of senescence, and ovariectomy is not well understood. We show that ovariectomy leads to CD28 loss on T cells and estrogen (E2) repletion and medicarpin (Med) inhibits this effect. We thus propose that Med/E2 prevents bone loss by delaying premature T cell senescence. INTRODUCTION: Estrogen deficiency triggers reproductive aging by accelerating the amplification of TNF-α-producing T cells, thereby leading to bone loss. To date, no study has been carried out to explain the relationship between CD4(+)CD28null T cells and ovariectomy or osteoporosis. We aim to determine the effect of Ovx on CD28 expression on T cells and effects of E2 and medicarpin (a pterocarpan phytoalexin) with proven osteoprotective effect on altered T cell responses. METHODS: Adult, female Balb/c mice were taken for the study. The groups were: sham, Ovx, Ovx + Med or E2. Treatments were given daily by oral gavage. At autopsy bone marrow and spleen were flushed out and cells labelled with antibodies for FACS analysis. Serum was collected for ELISA. RESULTS: In Ovx mice, Med/E2 at their respective osteoprotective doses resulted in thymus involution and lowered Ovx-induced increase in serum TNF-α level and its mRNA levels in the BM T cells. Med/E2 reduced BM and spleen CD4(+) T cell proliferation and prevented CD28 loss on CD4(+) T cells. Further, Med abrogated TNF-α-induced loss of CD28 expression in the BM T cells. CONCLUSIONS: To our knowledge this is the first report to determine the mechanism of CD28 loss on T cells as a result of ovariectomy. Our study demonstrates that Ovx leads to the generation of premature senescent CD4(+)CD28null T cells, an effect inhibited by E2 and Med. We propose that one of the mechanisms by which Med/E2 alleviates Ovx-induced bone loss is by delaying T cell senescence and enhancing CD28 expression.
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Conservadores de la Densidad Ósea/farmacología , Senescencia Celular/inmunología , Estradiol/farmacología , Osteoporosis/prevención & control , Pterocarpanos/farmacología , Subgrupos de Linfocitos T/efectos de los fármacos , Animales , Conservadores de la Densidad Ósea/uso terapéutico , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/inmunología , Antígenos CD28/metabolismo , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Células Cultivadas , Senescencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Estradiol/uso terapéutico , Femenino , Ribonucleoproteína Nuclear Heterogénea D0 , Ribonucleoproteína Heterogénea-Nuclear Grupo D/metabolismo , Ratones , Ratones Endogámicos BALB C , Tamaño de los Órganos/efectos de los fármacos , Osteoporosis/inmunología , Ovariectomía , Fosfoproteínas/metabolismo , Pterocarpanos/uso terapéutico , Proteínas de Unión al ARN/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Bazo/efectos de los fármacos , Bazo/inmunología , Subgrupos de Linfocitos T/inmunología , Timo/patología , Factor de Necrosis Tumoral alfa/metabolismo , NucleolinaRESUMEN
Human visceral leishmaniasis (VL) is frequently found in poor population who are suffering from malnutrition in endemic areas. Therefore, obviously they may have reduced levels of leptin due to reduction in number of adipocytes which are major source of leptin production. Human pathogenesis of VL and reduced levels of leptin both are associated with increase in Th2 type immune response, characterized by secretion of cytokines such as IL-4 and IL-10. Whereas, the protective immune response during visceral leishmaniasis is associated with effective Th1 type immune response characterized by secretion of IFN-γ, IL-2 and IL-12, which correlates with leptin induction of T cells polarizing to Th1 population and secretion of proinflammatory cytokines, and also inhibition of Th2 type response. Therefore, we hypothesized that leptin might be effective in treatment of visceral leishmaniasis alone or VL patients who have co-infection with other immune deficiency syndromes such as AIDS/diabetes/autoimmune disorders by regulation of Th1/Th2 homeostasis.
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Leishmaniasis Visceral/inmunología , Leishmaniasis Visceral/metabolismo , Leptina/metabolismo , Modelos Inmunológicos , Balance Th1 - Th2 , Adipocitos/metabolismo , Citocinas/inmunología , Humanos , Leptina/inmunologíaRESUMEN
UNLABELLED: The effect of quercetin C-glucoside (QCG) on osteoblast function in vitro and bone formation in vivo was investigated. QCG supplementation promoted peak bone mass achievement in growing rats and new bone formation in osteopenic rats. QCG has substantial oral bioavailability. Findings suggest a significant bone anabolic effect of QCG. INTRODUCTION: Recently, we showed that extracts of Ulmus wallichiana promoted peak bone mass achievement in growing rats and preserved trabecular bone mass and cortical bone strength in ovariectomized (OVx) rats. 3,3',4',5,7-Pentahydroxyflavone-6-C-ß-D-glucopyranoside, a QCG, is the most abundant bioactive compound of U. wallichiana extract. We hypothesize that QCG exerts bone anabolic effects by stimulating osteoblast function. METHODS: Osteoblast cultures were harvested from rat calvaria and bone marrow (BM) to study differentiation and mineralization. In vivo, growing female Sprague Dawley rats and OVx rats with osteopenia were administered QCG (5.0 or 10.0 mg kg(-1) day(-1)) orally for 12 weeks. Efficacy was evaluated by examining changes in bone microarchitecture using histomorphometric and microcomputed tomographic analyses and by determination of new bone formation by fluorescent labeling of bone. Plasma and BM levels of QCG were determined by high-performance liquid chromatography. RESULTS: QCG was much more potent than quercetin (Q) in stimulating osteoblast differentiation, and the effect of QCG was not mediated by estrogen receptors. In growing rats, QCG increased BM osteoprogenitors, bone mineral density, bone formation rate, and cortical deposition. In osteopenic rats, QCG treatment increased bone formation rate and improved trabecular microarchitecture. Comparison with the sham group (ovary intact) revealed significant restoration of trabecular bone in osteopenic rats treated with QCG. QCG levels in the BM were ~50% of that of the plasma levels. CONCLUSION: QCG stimulated modeling-directed bone accrual and exerted anabolic effects on osteopenic rats by direct stimulatory effect on osteoprogenitors likely due to substantial QCG delivery at tissue level following oral administration.