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1.
J Hand Surg Eur Vol ; 41(1): 22-34, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26586689

RESUMEN

Carpal instability is a complex and heterogeneous clinical condition. Management requires accurate identification of structural injury with an understanding of the resultant movement (kinematic) and load transfer (kinetic) failure. Static imaging techniques, such as plain film radiography, stress views, ultrasound, magnetic resonance, MR arthrography and computerized tomography arthrography, may accurately depict major wrist ligamentous injury. Dynamic ultrasound and videofluoroscopy may demonstrate dynamic instability and kinematic dysfunction. There is a growing evidence base for the diagnostic accuracy of these techniques in detecting intrinsic ligament tears, but there are limitations. Evidence of their efficacy and relevance in detection of non-dissociative carpal instability and extrinsic ligament tears is weak. Further research into the accuracy of existing imaging modalities is still required. Novel techniques, including four-dimensional computerized tomography and magnetic resonance, can evaluate both cross-sectional and functional carpal anatomy. This is a narrative review of level-III studies evaluating the role of imaging in carpal instability.


Asunto(s)
Articulaciones del Carpo , Diagnóstico por Imagen/métodos , Inestabilidad de la Articulación , Articulación de la Muñeca , Articulaciones del Carpo/diagnóstico por imagen , Articulaciones del Carpo/patología , Humanos , Imagenología Tridimensional , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/patología , Radiografía , Ultrasonografía , Articulación de la Muñeca/diagnóstico por imagen , Articulación de la Muñeca/patología
2.
Cardiovasc Intervent Radiol ; 39(5): 761-767, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26604114

RESUMEN

OBJECTIVE: To evaluate the diagnostic accuracy and safety of magnetic resonance imaging (MRI)-guided percutaneous biopsy of mediastinal masses performed using a wide-bore high-field scanner. MATERIALS AND METHODS: This is a retrospective study of 16 consecutive patients (8 male, 8 female; mean age 74 years) who underwent MRI-guided core needle biopsy of a mediastinal mass between February 2010 and January 2014. Size and location of lesion, approach taken, time for needle placement, overall duration of procedure, and post-procedural complications were evaluated. Technical success rates and correlation with surgical pathology (where available) were assessed. RESULTS: Target lesions were located in the anterior (n = 13), middle (n = 2), and posterior mediastinum (n = 1), respectively. Mean size was 7.2 cm (range 3.6-11 cm). Average time for needle placement was 9.4 min (range 3-18 min); average duration of entire procedure was 42 min (range 27-62 min). 2-5 core samples were obtained from each lesion (mean 2.6). Technical success rate was 100%, with specimens successfully obtained in all 16 patients. There were no immediate complications. Histopathology revealed malignancy in 12 cases (4 of which were surgically confirmed), benign lesions in 3 cases (1 of which was false negative following surgical resection), and one inconclusive specimen (treated as inaccurate since repeat CT-guided biopsy demonstrated thymic hyperplasia). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in our study were 92.3, 100, 100, 66.7, and 87.5%, respectively. CONCLUSION: MRI-guided mediastinal biopsy is a safe procedure with high diagnostic accuracy, which may offer a non-ionizing alternative to CT guidance.


Asunto(s)
Biopsia Guiada por Imagen/instrumentación , Imagen por Resonancia Magnética/instrumentación , Neoplasias del Mediastino/diagnóstico por imagen , Neoplasias del Mediastino/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Estudios de Factibilidad , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Imanes , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Adulto Joven
3.
Clin Radiol ; 70(3): 304-16, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25472466

RESUMEN

Functional imaging [diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE)] techniques combined with T2-weighted (T2W) and chemical-shift imaging (CSI), with or without urography, constitutes a comprehensive multiparametric (MP) MRI protocol of the kidneys. MP-MRI of the kidneys can be performed in a time-efficient manner. Breath-hold sequences and parallel imaging should be used to reduce examination time and improve image quality. Increased T2 signal intensity (SI) in a solid renal nodule is specific for renal cell carcinoma (RCC); whereas, low T2 SI can be seen in RCC, angiomyolipoma (AML), and haemorrhagic cysts. Low b-value DWI can replace conventional fat-suppressed T2W. DWI can be performed free-breathing (FB) with two b-values to reduce acquisition time without compromising imaging quality. RCC demonstrates restricted diffusion; however, restricted diffusion is commonly seen in AML and in chronic haemorrhage. CSI must be performed using the correct echo combination at 3 T or T2* effects can mimic intra-lesional fat. Two-dimensional (2D)-CSI has better image quality compared to three-dimensional (3D)-CSI, but volume averaging in small lesions can simulate intra-lesional fat using 2D techniques. SI decrease on CSI is present in both AML and clear cell RCC. Verification of internal enhancement with MRI can be challenging and is improved with image subtraction. Subtraction imaging is prone to errors related to spatial misregistration, which is ameliorated with expiratory phase imaging. SI ratios can be used to confirm subtle internal enhancement and enhancement curves are predictive of RCC subtype. MR urography using conventional extracellular gadolinium must account for T2* effects; however, gadoxetic acid enhanced urography is an alternative. The purpose of this review it to highlight important technical and interpretive pearls and pitfalls encountered with MP-MRI of solid renal masses.


Asunto(s)
Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Imagen por Resonancia Magnética/métodos , Angiomiolipoma/diagnóstico , Carcinoma de Células Renales/diagnóstico , Medios de Contraste , Quistes/diagnóstico , Quistes/patología , Imagen de Difusión por Resonancia Magnética/métodos , Gadolinio DTPA , Humanos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Riñón/patología , Curva ROC , Sensibilidad y Especificidad
4.
Br Poult Sci ; 55(1): 59-67, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24392856

RESUMEN

Abstract 1. The objective of the experiment was to determine the influence of age, sex and rearing system on Toll-like receptor 7 (TLR7) gene expression in gut, lung and lymphoid tissues and physiological responses to stress in male and female indigenous ducks of Tamil Nadu, India. 2. A total of 36 ducks (12 males and 24 females) were obtained from local farmers and tissue samples of gut tissues (duodenum, jejunum, ileum and caecum), lymphoid organs (spleen and bursa) and lungs were collected in RNAlater solution followed by RNA extraction. 3. After normalisation to ß-actin (endogenous control) qPCR analysis identified a significant effect of age, sex and rearing system on TLR7 expression in the ducks. 4. A significant up-regulation of TLR7 expression was observed in lungs, duodenum, jejunum, ileum and caecum of sexually mature (45 wk) compared with that of immature ducks (16 wk). Among sexes, male ducks had significantly higher TLR7 expression than female ducks. 5. Age and sex interactions were significant in lungs, duodenum, jejunum and caecum. Ducks reared in an extensive housing system showed significantly higher TLR7 expression in bursa, lungs, duodenum, ileum and caecum compared to intensively reared ducks. There were no effects of age, sex and rearing systems on TLR7 expression in the spleen. 6. The heterophil-to-lymphocyte ratio and serum corticosterone were higher in ducks reared on an intensive system compared with ducks from an extensive rearing system.


Asunto(s)
Patos/genética , Tracto Gastrointestinal/metabolismo , Regulación de la Expresión Génica , Vivienda para Animales/normas , Pulmón/metabolismo , Tejido Linfoide/metabolismo , Receptor Toll-Like 7/genética , Factores de Edad , Animales , Proteínas Aviares/genética , Proteínas Aviares/metabolismo , Patos/metabolismo , Femenino , India , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Factores Sexuales , Receptor Toll-Like 7/metabolismo
5.
Perspect Clin Res ; 3(2): 47-9, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22701819

RESUMEN

The Indian media in general, with the exception of a few domain expert journalists, have failed to comprehend the complexities involved in the clinical trial process. In the run up to the deadline-based coverage of a story, a majority of them fall short in conveying the right perspective to readers, but nevertheless they have been successful in sensationalizing an event in this arena. Possibly by unintended misrepresentation, or mostly out of ignorance of the nuances involved in the clinical trials process, the media has done more harm than good, and got away with it. On the other side, the industry has been reluctant to engage with the media in a meaningful dialog for too long now. It bears not only the consequences of damage to its professional reputation following such reportage, but also the repercussions of unnecessary clampdowns by the regulators. Science journalism in India has yet to rise as a profession.

6.
Ann Trop Med Parasitol ; 100(4): 315-26, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16762112

RESUMEN

In two complementary epidemiological surveys of villages on the Ugandan shoreline of Lake Victoria, the putative occurrence of intestinal schistosomiasis in the local infants (children aged < 3 years) was investigated. When, during the first survey, 136 mother-and-infant pairs from a total of 12 villages were studied, only 7% of the infants but 45% of the mothers were found to be egg-patent for Schistosoma mansoni infection. The use of dipstick tests for urine-circulating cathodic antigen indicated, however, a much higher prevalence, of approximately 40%, among the infants. In the second survey, urine samples and multiple, not single, stool samples were collected from another 19 mother-and-infant pairs in two of the 12 study villages (Bugoto and Bwondha), and a standardized questionnaire was implemented. The prevalence of egg-patent infection was then found to be markedly higher in the study infants from Bugoto (86%) than in those from Bwondha (25%). A greater level of mother-and-infant water contact, a higher abundance of (infected) Biomphalaria choanomphala, and an unusual lakeshore topology may explain why S. mansoni infection was so much more common in the Bugoto subjects than in the Bwondha. All but one of the infants studied in the second survey were found to be anaemic (with <110 g haemoglobin/litre). Taken together, these children were less likely to be found infected with hookworm (16%), Hymenolepis nana (11%) or Trichuris trichiura (5%) than with S. mansoni (47%). Infection with the parasites causing intestinal schistosomiasis can be common among the infants living in these lakeshore villages. Although the immediate and later-life clinical impacts of such infection have yet to be elucidated, such infants would probably benefit from regular de-worming. Mothers should be strongly encouraged to visit the nearest health-services clinic, with their infants, for any necessary anthelmintic treatment.


Asunto(s)
Esquistosomiasis mansoni/epidemiología , Animales , Biomphalaria , Preescolar , Vectores de Enfermedades , Heces/parasitología , Femenino , Hemoglobinas/análisis , Humanos , Higiene , Lactante , Masculino , Madres , Recuento de Huevos de Parásitos/métodos , Vigilancia de la Población/métodos , Prevalencia , Factores de Riesgo , Salud Rural , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/parasitología , Esquistosomiasis mansoni/orina , Distribución por Sexo , Uganda/epidemiología
7.
Chemotherapy ; 52(2): 60-5, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16462139

RESUMEN

BACKGROUND: The common plant bioflavonoid, quercetin, is cytotoxic to various tumor cell lines, particularly breast cancer, by affecting the protein-kinase-C-dependent signal pathways and by cell cycle regulation. However, its role in breast cancer metastasis has not been studied so far. Increased uPA activity is evident in highly metastatic breast cancer, which is calcium dependent. METHODS: MDA MB 231 cells were treated with various concentrations of quercetin (15-45 microg/ml). The cytotoxic effect of quercetin was assessed by MTT assay and DNA fragmentation analysis. Intracellular calcium levels were measured using Fura-2, a specific Ca2+ fluorescence indicator. Calcium uptake and release in cells treated with quercetin were measured using radioactive 45Ca2+. Urokinase enzyme activity was assayed by a casein zymogram. RESULTS: Quercetin elicited dose- and time-dependent cytotoxicity as evidenced by the MTT assay. The maximum effect was observed at 48 h with a quercetin concentration of (45 microg/ml). DNA agarose gel electrophoresis showed dose-dependent DNA fragmentation on quercetin treatment. Quercetin caused significant depletion of cytosolic calcium levels and decreased calcium uptake from the intracellular stores. Casein zymogram showed a marked reduction of urokinase activity as evident by clear lysis bands on a dark background on treatment with quercetin. CONCLUSION: Quercetin was found to exhibit cytotoxicity in the highly invasive breast cancer cell line MDA MB 231 in a dose- and time-dependent manner. Quercetin inhibited calcium dependent urokinase activity and hence may prove to be an effective antimetastatic agent.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Calcio/metabolismo , Quercetina/farmacología , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores , Adenocarcinoma , Neoplasias de la Mama , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Fragmentación del ADN , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Agar , Femenino , Humanos
8.
J Environ Sci Eng ; 47(1): 53-8, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16669336

RESUMEN

In the present study the environmental effects on herbivores mammals in and around Coal-fired power plant were studied by collecting the various milk samples of Cow and Buffalo in clean polyethylene bottles. Milk samples collected at five different locations along the banks of the Paravanaru river in and around Neyveli area. These samples were prepared for trace metal determination. The concentration of trace metals (Cu, Zn, Ni, Cd, Cr, Mn, Co and Hg) were determined by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) and Cold Vapour Atomic Absorption Spectrometry (CVAAS). It is observed that the samples contain greater amounts of trace metals than that in the unexposed areas. Obviously the milk samples are contaminated with these metals due to fly ash released in such environment.


Asunto(s)
Contaminantes Ambientales/análisis , Metales Pesados/análisis , Leche/química , Centrales Eléctricas , Oligoelementos/análisis , Animales , Bovinos , Carbón Mineral , Monitoreo del Ambiente , India
9.
J Environ Sci Eng ; 47(3): 182-7, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16841456

RESUMEN

Infrared spectra of vegetative parts (leaf, stem and flower) of the weed plant Parthenium hysterophorus Linn. was recorded. The observed frequencies in the region 4000-400 cm(-1) have been recorded along with vibrational assignments and intensities. Probable assignments of the bands were made with respect to the components present in the samples.


Asunto(s)
Asteraceae/química , Flores/química , Hojas de la Planta/química , Tallos de la Planta/química , Espectroscopía Infrarroja por Transformada de Fourier
10.
J Periodontol ; 73(1): 79-85, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11846203

RESUMEN

BACKGROUND: Tetracyclines, particularly doxycycline (Doxy), and their non-antimicrobial chemically-modified derivatives (CMTs) inhibit the activities of human matrix metalloproteinases (MMPs), and reduce the severity and progression of periodontal disease in animal models and humans. In this study, the effects of Doxy and CMT-1, -3, and -5 on proteolytic, serpinolytic, and progelatinase-B activation activities of potent periodontopathogens were studied. METHODS: The effect of Doxy and CMTs (0.5 to 50 microM) on proteolytic activities were investigated by incubating bacteria with chromogenic substrates or human serum albumin. A collagenolytic fraction of Porphyromonas gingivalis was used to evaluate the effect of these substances on collagenolytic (type I collagen) and serpinolytic (alpha1-proteinase inhibitor) activities. Lastly, the effect of Doxy on progelatinase-B (pro-MMP-9) activation by purified proteinases from P. gingivalis and Treponema denticola was investigated by SDS-PAGE/Western immunoblotting. RESULTS: Doxy and CMTs, except CMT-5 which lacks the structural elements required for cation chelation, inhibited Arg- and Lys-gingipain activities as well as collagenolytic activity of P. gingivalis. Doxy and CMTs did not markedly affect the chymotrypsin-like activity of T. denticola but inhibited its trypsin-like activity. In addition, degradation of human serum albumin by cells of P. gingivalis and T. denticola was strongly inhibited by Doxy and CMT-1. Doxy and CMT-1 also inhibited the inactivation of alpha1-proteinase inhibitor (serpinolytic activity) by a collagenolytic fraction of P. gingivalis. Lastly, Doxy prevented the latent to active conversion of human neutrophil progelatinase-B (pro-MMP-9) by Arg-gingipains A/B of P. gingivalis but not by the chymotrypsin-like proteinase of T. denticola. CONCLUSIONS: Data from this study suggest that Doxy and CMTs have the potential to inhibit the periodontopathogenic bacterial proteinases, which contribute to tissue destruction cascades during periodontitis directly and indirectly by triggering the host response.


Asunto(s)
Antibacterianos/farmacología , Doxiciclina/farmacología , Inhibidores Enzimáticos/farmacología , Precursores Enzimáticos/antagonistas & inhibidores , Gelatinasas/antagonistas & inhibidores , Metaloendopeptidasas/antagonistas & inhibidores , Inhibidores de Proteasas/farmacología , Inhibidores de Serina Proteinasa/farmacología , Serpinas/farmacología , Adhesinas Bacterianas/metabolismo , Western Blotting , Compuestos Cromogénicos , Quimotripsina/antagonistas & inhibidores , Cisteína Endopeptidasas/metabolismo , Inhibidores de Cisteína Proteinasa/farmacología , Electroforesis en Gel de Poliacrilamida , Cisteína-Endopeptidasas Gingipaínas , Hemaglutininas/metabolismo , Humanos , Inhibidores de la Metaloproteinasa de la Matriz , Neutrófilos/enzimología , Porphyromonas gingivalis/enzimología , Albúmina Sérica , Tetraciclina/farmacología , Tetraciclinas/farmacología , Treponema/enzimología , Inhibidores de Tripsina/farmacología , alfa 1-Antitripsina/farmacología
11.
Indian J Environ Health ; 44(1): 37-40, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12968723

RESUMEN

The exhaust gases from automobiles constitute about 75% of air pollution. Among the various pollutants emitted from vehicles, CO is the primary pollutant and very toxic one. The CO monitor method was used to predict the CO level in Chidambaram town. From the study it is evident that the pollution level is closely related to the density of motor vehicles on the roads. With increase in number of motor vehicles pollution level also increases which pollutes the roadside environment severely in future.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monóxido de Carbono/análisis , Exposición a Riesgos Ambientales/efectos adversos , Emisiones de Vehículos/análisis , Contaminantes Atmosféricos/efectos adversos , Monitoreo del Ambiente/métodos , Humanos , India , Trastornos Respiratorios/etiología , Emisiones de Vehículos/efectos adversos
12.
J Periodontol ; 72(8): 1069-77, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11525440

RESUMEN

BACKGROUND: Chemically modified non-antimicrobial tetracyclines (CMTs) have been shown to inhibit pathologically elevated collagenase (and other matrix metalloproteinase, MMP) activity and bone resorption in vivo and in vitro. METHODS: In the current study, suboptimal doses of CMT-8 (a non-antimicrobial chemically modified doxycycline) and a bisphosphonate (clodronate, an anti-bone resorption compound) were administered daily, either as a single agent or as a combination therapy, to rats with experimental periodontitis induced by repeated injection of bacterial endotoxin (LPS) into the gingiva. At the end of the 1-week protocol, the gingival tissues were dissected, extracted, and the extracts analyzed for MMPs (collagenases and gelatinases) and for elastase, and the defleshed jaws were morphometrically analyzed for alveolar bone loss. RESULTS: LPS injection significantly (P<0.001) increased alveolar bone loss and increased collagenase (MMP-8), gelatinase (MMP-9), and elastase activities. Treatment of the LPS-injected rats with suboptimal CMT-8 alone or suboptimal clodronate alone produced slight reductions in the tissue-destructive proteinases and no significant reductions in alveolar bone loss. However, a combination of suboptimal CMT-8 and clodronate "normalized" the pathologically elevated levels of MMPs, elastase, and alveolar bone loss, indicating synergistic inhibition of tissue breakdown in this animal model of periodontitis. CONCLUSIONS: Combination of a CMT and a bisphosphonate may be a useful treatment to optimally suppress periodontal destruction and tooth loss and in other tissue-destructive inflammatory diseases such as arthritis.


Asunto(s)
Pérdida de Hueso Alveolar/prevención & control , Ácido Clodrónico/uso terapéutico , Inhibidores de la Metaloproteinasa de la Matriz , Inhibidores de Proteasas/uso terapéutico , Tetraciclinas/uso terapéutico , Pérdida de Hueso Alveolar/enzimología , Pérdida de Hueso Alveolar/microbiología , Análisis de Varianza , Animales , Sinergismo Farmacológico , Quimioterapia Combinada , Gelatinasas/antagonistas & inhibidores , Lipopolisacáridos/efectos adversos , Lipopolisacáridos/farmacología , Masculino , Elastasa Pancreática/antagonistas & inhibidores , Periodontitis/inducido químicamente , Periodontitis/microbiología , Ratas , Ratas Sprague-Dawley , Pérdida de Diente/prevención & control
13.
Curr Med Chem ; 8(3): 243-52, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11172678

RESUMEN

CMTs are analogs of tetracyclines, which are chemically modified to eliminate their antimicrobial efficacy but which retain their inhibitory activity against matrix metalloproteinases. These compounds have been found to inhibit connective tissue breakdown in animal models of diseases such as periodontitis, arthritis and cancer. Because CMTs exhibit different in vivo efficacy in these various models of disease, the current study compared their pharmacokinetics and other properties as follows: Adult male Sprague-Dawley rats were administered by oral gavage a single dose of 5mg of different CMTs suspended in 1 ml 2% carboxymethyl-cellulose, and blood samples were collected from 1-48 hours after dosing. The sera were extracted, then analyzed by HPLC using a C-18 reverse-phase column. The results showed that the peak concentrations (C(max)) in rat sera 1-12 hours after oral administration of CMTs -1, -2,-3, -4,-5,-6,-7,-8 and doxycycline were 5.5, 0.7, 4.6, 6.2, 0.8, 0.7, 9.0 (note: the 3 peaks detected for CMT-7 were combined), 15.0 and 0.9 microg/ml, respectively. Their in vivo half-lives (t(1/2)) were 11, 5, 22, 11, 32, 15, 37, 38, and 17 hours, respectively. Of the anticollagenase CMTs tested, CMT-8 showed the greatest C(max) and t(1/2)values, followed by CMTs-3, -1, -4, and perhaps -7; CMTs-2, -5, and -6 exhibited much lower levels in serum. The relative lipophilicities of the 8 CMTs and doxycycline were tested by examining their extractability in octanol. The results showed that CMT-2, -5, and -6 had the lowest partition coefficients using this organic solvent, while CMT-3 was the most lipophilic. The lipophilicity of the different CMTs was also positively correlated (r(2)=0.767, P<0.05) to peak serum concentrations (C(max)), but not to their serum half-lives (r(2)=0.25,P=0.49). This property of the different CMTs was also found to be positively correlated to their ability to enter into human whole blood cells in vitro (r2=0.95, P<0.001). Since CMT-8, as well as CMTs-3 and -1, consistently exhibited the greatest in vivo efficacy in animal models of tissue breakdown, this may reflect, at least in part, their favorable pharmacokinetics and tissue uptake.


Asunto(s)
Tetraciclinas/química , Tetraciclinas/farmacocinética , Administración Oral , Animales , Transporte Biológico , Células Sanguíneas/metabolismo , Doxiciclina/sangre , Doxiciclina/farmacocinética , Semivida , Humanos , Masculino , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Análisis de Regresión , Relación Estructura-Actividad , Tetraciclinas/sangre
14.
Curr Med Chem ; 8(3): 253-6, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11172679

RESUMEN

CMT-3 is a NON-ANTIMICROBIAL tetracycline (TC), chemically modified to enhance its collagenase-inhibitory property. This property is therapeutically useful in treating diseases such as periodontitis, cancer and arthritis. CMT-3 was labeled with tritium [(3)H] at Carbon 7. Four adult male Sprague-Dawley rats (350--400 g body weight) were gavaged once with a mixture of cold CMT-3 and [(3)H] CMT-3 (750 microCi). An additional four rats were gavaged for 2 days with cold CMT-3(15 mg/Kg/day) and on the third day the rats were gavaged with a mixture of cold and [(2)H] CMT-3 (750 microCi); and all 8 rats were placed in the metabolic cages. Blood samples were collected from the tail at multiple intervals from 1--14 hr after [(3)H] CMT-3 administration. At 14 hr, the rats were anesthetized, euthanized and various tissues including visceral organs were removed and weighed. The contents of GI tracts were emptied and added to the fecal pellets and weighed. The urine samples were collected and volume measured. Each tissue or organ was minced finely with scissors and 100 mg of tissue was digested in 1 ml of Tissue-solv (Packard Lab), for 4 hrs at 37 degrees C and each sample was diluted up to 10 ml of distilled water. A 100 microl aliquot was taken and diluted with an equal volume of glacial acetic acid, 10 ml of Atom-lite was added and counted for radioactivity in a liquid scintillation spectrometer. This biodistribution study revealed that over 14 hrs, 54% and 3% of [(3)H] CMT-3 were excreted in the feces and urine, respectively. The serum [(3)H] CMT-3 count reached its maximum value at about 12 hours. The tissues retained the CMTs as follow: muscle (23%); skin (2.41%); bone (1.72%); and the brain retained 0.21% of the label. The radioactive CMT-3 in the visceral organs is as follows: GI tract - its contents (8.9%); heart (0.41%), testis (0.41%); lungs >(0.16%); spleen (0.08%); liver (0.03%); kidneys > (0.02%).


Asunto(s)
Tetraciclinas/farmacocinética , Administración Oral , Animales , Radioisótopos de Carbono , Sistema Digestivo/metabolismo , Heces/química , Masculino , Tasa de Depuración Metabólica , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/sangre , Inhibidores de Proteasas/farmacocinética , Técnica de Dilución de Radioisótopos , Ratas , Ratas Sprague-Dawley , Tetraciclinas/administración & dosificación , Tetraciclinas/sangre , Distribución Tisular
15.
Curr Med Chem ; 8(3): 281-94, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11172683

RESUMEN

Cutaneous wound healing is a complex process involving interactions of various cell types. Skin, in addition to certain other organs, is dependent on estrogen; and estrogen-deficiency is associated with impaired wound healing. Wound healing involves the action of collagenolytic matrix metalloproteinases (MMPs). We investigated the expression and localization of collagenolytic MMPs -8 and -13 by collagenase activity assay, Western immunoblot analysis, in situ hybridization and immunohistochemical staining as well as type I collagen by hydroxyproline content analysis and immunohistochemical staining in cutaneous wounds from aged Sham and ovarioectomized (OVX) rats. After wounding, OVX rats were treated with either placebo, chemically modified tetracycline-8 (CMT-8) or estrogen. We found that MMP-8 and MMP-13 mRNA were expressed in wound epithelium of all samples examined as evidenced by in situ hybridization. Type I collagen, which was abundant in all groups examined, was decreased in OVX rats, but was increased by both CMT-8 and estrogen treatments to the level of Sham group. Hydroxyproline analysis revealed similar results. Western blot data showed that all forms of MMP-8 and MMP-13 were clearly reduced in the CMT-8 treated group compared to OVX. Analysis of collagenolytic activity confirmed the decreased collagenolysis in skin wound extracts from CMT-treated rats when compared with skin wound extracts from OVX rats. Our results show for the first time that MMP-8 mRNA and protein are expressed in rat wound epithelium. We further show that CMT-8 and estrogen have a beneficial effect on skin wound healing in OVX rats by increasing the collagen content and reducing the MMP-mediated collagenolysis.


Asunto(s)
Colágeno/genética , Colagenasas/genética , Estrógenos/farmacología , Metaloproteinasa 8 de la Matriz/genética , Inhibidores de Proteasas/farmacología , Tetraciclinas/farmacología , Transcripción Genética/efectos de los fármacos , Cicatrización de Heridas/fisiología , Animales , Colagenasas/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Células Epiteliales/fisiología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Hibridación in Situ , Metaloproteinasa 13 de la Matriz , Ovariectomía , Ratas , Ratas Sprague-Dawley , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones/fisiopatología
16.
Curr Med Chem ; 8(3): 295-303, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11172684

RESUMEN

Recent studies have demonstrated that tetracyclines can reduce bone loss in the ovariectomized (OVX) rat model of osteoporosis. In the current study, a non-antimicrobial, chemically modified doxycycline (CMT-8), alone or in combination with a bisphosphonate (Clodronate), was evaluated in this model. Forty-two, 6month old, female rats were randomly assigned to the following groups, (6/ group): a) sham/vehicle, b) OVX/vehicle; c) OVX/1 mg/day CMT-8; d) OVX/2 mg/day CMT-8, e) OVX/1 mg/week Clodronate; and f) OVX/1 mg/day CMT-8 + 1 mg/week Clodronate, CMT-8 was administered by oral gavage, Clodronate injected S/C. Following sham surgery or OVX, the rats were treated for 90 days with CMT-8 or vehicle alone, injected at three different times with fluorochrome labels, the rats were sacrificed, and the tibiae excised for analysis by dynamic bone histomorphometry. Femurs were aseptically removed and analyzed for collagen, collagenase and osteopontin mRNAs by Northern and dot blot analysis. As expected, OVX decreased trabecular bone volume (BV/TV by 73.8% vs. sham p<.01), and also reduced trabecular thickness, numbers, and increased spacing. Bone loss in the OVX animals was partially prevented with either 2 mg/day CMT-8 or 1 mg/wk Clodronate (p<.01), while the 1 mg/day CMT-8 had no effect. Interestingly, the efficacy of the combination therapy of CMT-8 and Clodronate was significantly better than either treatment by itself, maintaining bone mass and structural indices at levels identical to sham values. OVX rats mRNA for collagen, collagenase and osteopontin were elevated indicating high-turnover bone loss. Only COMBO therapy significantly reduced the collagenase and osteopontin mRNA. In summary, CMT-8 mono-therapy (2 mg) alone partially inhibited bone loss in this animal model of osteoporosis. However, 1 mg/day (CMT-8) monotherapy had no effect on bone loss or bone mRNA levels and when combined with Clodronate, interacted to increase efficacy. Thus, a combination of a suboptimal dose of CMT-8 and a bisphosphonate appears to increase the amount of bone by suppressing resorption in a model of osteoporosis.


Asunto(s)
Densidad Ósea/efectos de los fármacos , Ácido Clodrónico/farmacología , Osteoporosis/prevención & control , Tetraciclinas/farmacología , Animales , Huesos/efectos de los fármacos , Huesos/fisiología , Huesos/fisiopatología , Ácido Clodrónico/uso terapéutico , Colágeno/genética , Colagenasas/genética , Modelos Animales de Enfermedad , Doxiciclina/análogos & derivados , Quimioterapia Combinada , Femenino , Fémur , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Osteopontina , Ovariectomía , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Sialoglicoproteínas/genética , Tetraciclinas/sangre , Tetraciclinas/uso terapéutico , Transcripción Genética/efectos de los fármacos
17.
Curr Med Chem ; 8(3): 305-16, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11172685

RESUMEN

Diabetes mellitus in rats is characterized by excessive activity of several matrix metalloproteinases (MMPs), notably collagenase(s) and gelatinase(s), in skin, gingiva, and other tissues. A number of tetracyclines (TCs), both antimicrobial compounds as well as chemically modified non-antimicrobial TC analogues (CMTs) are known to possess potent inhibitory activity against these enzymes. Three conventional antimicrobial TCs and six CMTs were used in this study. In vitro, doxycycline was shown to possess higher inhibitory capacity (i.e. lower IC(max)) against diabetic rat skin collagenase than either minocycline or tetracycline HCl. Addition of excess zinc partially reversed the proteinase inhibition by TCs. In vivo, using rats made diabetic with streptozotocin (STZ), oral administration of various TCs led to decreased weight loss and substantial reductions in the activity of both skin collagenase and skin gelatinase (primarily MMP-9, 92 kDa) without affecting blood glucose. Using an in vitro spectrophotometric technique, the Zn(++) reactivity of several CMTs was assessed and found to be positively related to the potency of these compounds as MMP inhibitors. One particular CMT (CMT-5, pyrazole analogue), which is neither antimicrobial nor capable of binding metal cations, did not inhibit the MMPs. TCs have potential utility in management of diabetic complications mediated by excessive activity of MMPs.


Asunto(s)
Diabetes Mellitus Experimental/enzimología , Metaloproteinasas de la Matriz/metabolismo , Tetraciclinas/farmacología , Animales , Colágeno/metabolismo , Colagenasas/metabolismo , Gelatinasas/metabolismo , Encía/enzimología , Masculino , Inhibidores de la Metaloproteinasa de la Matriz , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Piel/enzimología , Relación Estructura-Actividad , Tetraciclina/farmacología , Tetraciclinas/química
18.
Indian J Environ Health ; 43(4): 144-7, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12395517

RESUMEN

The exhaust gases from automobiles constitute about 75% of air pollution. Among the various pollutants emitted from vehicles, CO is the primary pollutant and very toxic one. The CO monitor method was used to measure the CO level in Chidambaram town. From the study, it is evident that the CO level is closely related to the density of motor vehicles plying on the roads. With increase in number of motor vehicles CO level also increases, which pollutes the roadside environment severely in future.


Asunto(s)
Monóxido de Carbono/análisis , Emisiones de Vehículos/análisis , Ciudades , Monitoreo del Ambiente , India , Vehículos a Motor
19.
Br Poult Sci ; 41(2): 178-81, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10890214

RESUMEN

1. The hatchability of checked Leghorn and broiler parent hatching eggs was significantly improved by shell treatment: smearing with synthetic adhesive resin (Fevicol), or pasting cellophane tape or insulation tape over the checked portion of the shell. 2. Shell damage reduced hatchability by increasing evaporative loss, leading to embryonic dehydration. 3. Relative chick weight, expressed as a percentage of egg weight was lower in untreated checked eggs but comparable between intact and shell-treated hatching eggs. 4. The cost of chick production can be reduced by shell treatment of checked hatching eggs, especially in broiler parent eggs.


Asunto(s)
Embrión de Pollo/crecimiento & desarrollo , Cáscara de Huevo/lesiones , Animales , Peso Corporal , Celofán , Embrión de Pollo/fisiología , Femenino , Masculino , Distribución Aleatoria , Resinas de Plantas
20.
J Electron Microsc (Tokyo) ; 48(4): 465-9, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10510861

RESUMEN

Postmenopausal oestrogen deficiency results in bone loss (osteoporosis) in humans and experimental animals. The loss of trabecular bone in the ovariectomized (OVX) rat provides a useful experimental model of post-menopausal osteoporosis. At 5 months after ovariectomy of 3-month-old female rats, the mid and distal femurs and maxillae were dissected and processed for quantitative backscattered electron microscopic examinations. Histomorphometric analysis of femurs in OVX rats showed significant loss in metaphyseal trabecular bone areas compared with sham-operated controls; no significant bone loss was observed in the cortical bone areas of mid-diaphyses in OVX rats. Net bone areas in the maxillae of OVX rats was similar to that of sham-operated controls. Bone structure of maxillae in OVX rats was also similar to that in controls. Our results suggest that, in this animal model of osteoporosis, prominent bone loss occurs mainly in the bone areas formed by endochondral ossification such as distal femurs, but those areas formed by intramembranous ossification such as mid-femurs and maxillae sustained less effects by OVX.


Asunto(s)
Huesos/ultraestructura , Ovariectomía/efectos adversos , Animales , Modelos Animales de Enfermedad , Estrógenos/deficiencia , Femenino , Fémur/ultraestructura , Humanos , Maxilar/ultraestructura , Microscopía Electrónica/métodos , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/patología , Ratas , Ratas Sprague-Dawley , Dispersión de Radiación
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