RESUMO
Organic soils have low sorption capacities for phosphorus (P), and may pose a risk of P loss to water if P applications to these soils coincide with runoff events. Little is known about the magnitude of exports of P in overland flow following application of P fertiliser onto these soils, or on the influence of the frequency on P losses and persistence. The number of P fertiliser applications was surveyed across 39 commercial farms to assess current practice and inform the design of a rainfall runoff experiment to evaluate the effect of frequency of P applications on losses and persistence across time. Superphosphate (16% P) was applied in single (equivalent to 30 and 55â¯kgâ¯P ha-1 applied at day 0) and split (equivalent to 15 and 27.5â¯kgâ¯P ha-1 applied in two doses at days 0 and 55) applications to an organic soil inclined at a slope of 6% in a rainfall simulator experiment. The surface runoff of dissolved reactive phosphorus (DRP) was measured in controlled 30-min rainfall simulations conducted intermittently over an 85-day period. The DRP losses in surface runoff after the first rainfall event were 44.6 and 97.8â¯mgâ¯L-1 for single applications of 30 and 55â¯kgâ¯ha-1, respectively, and 13.3 and 21.8â¯mgâ¯L-1 for the same rates split in two doses, indicating that single P applications had disproportionately bigger impacts on losses than split applications. This supports the idea that frequent, but smaller, P applications can minimise the impact of fertilisation on waters. Dissolved reactive P concentrations remained significantly higher than those from the control samples until the end the experiment for almost all the P treatments, highlighting the long-lasting effects of added P and the elevated risk of P losses on organic soils. For climates with frequent rainfall events, which are likely to coincide with fertiliser applications, smaller but more frequent P applications can reduce the risk of P transfer as opposed to one single application.
Assuntos
Fertilizantes , Fósforo , Esterco , Chuva , Solo , Movimentos da ÁguaRESUMO
Boneless pork loins (n=112) were used to test the influence of dietary manganese (Mn) inclusion level on pork quality traits during retail display. Crossbred barrows and gilts were fed diets formulated with 0, 20, 40, 80, 160, or 320ppm Mn from Availa(®)Mn (AvMn; a Mn-amino acid complex) from 23.8 to 106.8kg live weight. At approximately 48h postmortem, boneless pork loins were fabricated into longissimus thoracis et lumborum (LM) chops, which were subsequently placed in open-topped, coffin-chest display cases (2.6°C) under continuous warm-white, fluorescent lighting (1600lx) for 7days. Dietary Mn level had no effect on LM pH (P=0.47), purge volume (P=0.60) and loss (P=0.53), or moisture loss (P=0.95) during retail display. Chops from pigs fed 80ppm Mn received higher (P<0.05) American and Japanese color scores than pigs fed 0 and 40ppm Mn. Even though the LM from pigs fed 80, 160, and 320ppm Mn tended to be darker (lower L(∗) values; P=0.07) than chops from pigs fed 40ppm Mn, a(∗) (redness) and b(∗) (yellowness) values, as well as hue angle and chroma, were not (P⩾0.19) affected by dietary Mn. On days 0 and 1, the reflectance ratio of 630nm/580nm was similar (P>0.05) among dietary Mn supplementation levels; yet, by day 4 of retail display, chops from pigs fed 80ppm Mn had higher (P<0.05) reflectance ratios than chops from pigs fed 0, 20, 40, and 160ppm, whereas LM chops from pigs fed 40ppm Mn had lower (P<0.05) reflectance ratios than all other dietary treatments on day 7 (Mn supplementation level×display day; P=0.04). Although TBARS were greater (P<0.001) on day 7 than 0 of retail display, TBARS values did not (P=0.43) differ among dietary Mn levels. Results indicate that supplementing swine diets with 80ppm Mn may improve pork color during retail display without increasing the likelihood of lipid oxidation.
RESUMO
Three hundred sixteen crossbred pigs were used in two experiments to determine the effect of supplemental manganese source and dietary inclusion level during the growing-finishing period on performance and pork carcass characteristics. All pigs were blocked by weight, and treatments were assigned randomly to pens within blocks. In Exp. 1, a total of 20 pens (five pigs/pen) was randomly assigned to one of five dietary treatments consisting of control grower and finisher diets, or control diets supplemented with either 350 or 700 ppm (as-fed basis) Mn either from MnSO4 or a Mn AA complex (MnAA). In Exp. 2, a total of 36 pens (six pigs per pen) was assigned randomly to one of six dietary treatments formulated with 0, 20, 40, 80, 160, or 320 ppm (as-fed basis) Mn from MnAA. Pigs were slaughtered when the lightest block averaged 120.0 kg (Exp. 1) or at a mean BW of 106.8 kg (Exp. 2). Neither ADG nor ADFI was affected (P > 0.21) by Mn source or high inclusion level (Exp. 1); however, across the entire feeding trial, pigs consuming 320 ppm Mn from MnAA were more (P < 0.04) efficient than pigs fed diets formulated with 20 to 160 ppm Mn from MnAA (Exp. 2). Color scores did not differ (P > 0.79) at the low inclusion (20 to 320 ppm Mn) levels used in Exp. 2; however, in Exp. 1, the LM from pigs fed Mn tended to receive higher (P = 0.10) American color scores than that of pigs fed the control diet, and Japanese color scores were higher for the LM from pigs fed diets containing 350 ppm Mn from MnAA than 350 Mn from ppm MnSO4 or 700 ppm Mn from MnAA (source x inclusion level; P = 0.04; Exp. 2). Chops of pigs fed 350 ppm Mn from MnAA were darker than the LM of pigs fed 350 ppm Mn from MnSO4, and 700 ppm Mn from MnAA diets (source x inclusion level; P = 0.03; Exp. 1), but L* values were not (P = 0.76) affected by lower MnAA inclusion levels (Exp. 2). Even though the LM tended to became redder as dietary MnAA inclusion level increased from 20 to 320 ppm Mn (linear effect; P < 0.10), a* values were not (P = 0.71) altered by including 350 or 700 ppm Mn (Exp. 1). Chops of pigs fed MnAA had lower cooking losses (P = 0.01) and shear force values (P = 0.07) after 2 d of aging than did chops from pigs fed diets formulated with MnSO4. Results from these experiments indicate that feeding 320 to 350 ppm Mn from MnAA during the growing-finishing period may enhance pork quality without adversely affecting pig performance or carcass composition.
Assuntos
Composição Corporal/efeitos dos fármacos , Manganês/farmacologia , Carne/normas , Suínos/crescimento & desenvolvimento , Aumento de Peso/efeitos dos fármacos , Ração Animal , Animais , Dieta , Suplementos Nutricionais , Feminino , Masculino , Manganês/administração & dosagemRESUMO
OBJECTIVE: To determine whether consumption of five portions of fruit and vegetables per day reduces the enhancement of oxidative stress induced by consumption of fish oil. SUBJECTS: A total of 18 free-living healthy smoking volunteers, aged 18-63 y, were recruited by posters and e-mail in The University of Reading, and by leaflets in local shops. DESIGN: A prospective study. SETTING: Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, Whiteknights PO Box 226, Reading RG6 6AP, UK. INTERVENTION: All subjects consumed a daily supplement of 4 x 1 g fish oil capsules for 9 weeks. After 3 weeks, they consumed an additional five portions of fruits and vegetables per day, and then they returned to their normal diet for the last 3 weeks of the study. Fasting blood samples were taken at the ends of weeks 0, 3, 6 and 9. RESULTS: The plasma concentrations of ascorbic acid, lutein, beta-cryptoxanthin, alpha-carotene and beta-carotene all significantly increased when fruit and vegetable intake was enhanced (P<0.05). Plasma concentrations of alpha-tocopherol, retinol and uric acid did not change significantly during the period of increased fruit and vegetable consumption. Plasma oxidative stability, assessed by the oxygen radical absorbance capacity (ORAC) assay, also increased from weeks 3-6 (P<0.001) but not in association with increases in measured antioxidants. Lag phase before oxidation of low-density lipoprotein (LDL) significantly decreased in the first 3 weeks of the study, reflecting the incorporation of EPA and DHA into LDL (P<0.0001). Subsequent enhanced fruit and vegetable consumption significantly reduced the susceptibility of LDL to oxidation (P<0.005). CONCLUSION: Fish oil reduced the oxidative stability of plasma and LDL, but the effects were partially offset by the increased consumption of fruit and vegetables.
Assuntos
Antioxidantes/metabolismo , Óleos de Peixe/administração & dosagem , Frutas , Lipoproteínas LDL/metabolismo , Fumar/sangue , Verduras , Adolescente , Adulto , Estudos Cross-Over , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Estudos ProspectivosRESUMO
In this prospective cohort study, minocycline-ethylenediaminetetraacetate (M-EDTA) was used as a lock solution in indwelling ports inserted in 14 children with cancer. No port infections, thrombotic events, or other adverse events were observed, compared with 10 port infections that occurred in 48 control patients whose ports were flushed with heparin. M-EDTA is a promising lock solution in long-term catheters.
Assuntos
Antibacterianos/uso terapêutico , Ácido Edético/uso terapêutico , Minociclina/uso terapêutico , Neoplasias/complicações , Infecções Relacionadas à Prótese/prevenção & controle , Trombose/prevenção & controle , Cateteres de Demora , Quelantes/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
Accurate serum iron and total iron binding capacity (TIBC) measurements may be useful in acute iron overdoses. Two alumina column TIBC methods were found to measure increased TIBC when free iron was present. A homogeneous TIBC method gave consistent results until iron concentrations exceeded 500 micrograms/dL (90 mumol/L), when it began to underestimate the TIBC. Serious iron overdoses require chelation therapy with deferoxamine. Iron recovery was reduced by up to 50% for all 3 methods with clinically achievable concentrations of deferoxamine 8,400 micrograms/dL (150 mumol/L). TIBC measurements by both alumina column methods were reduced by deferoxamine in the presence of free iron and unaffected when the iron concentration was less than the TIBC. The homogeneous TIBC method yielded falsely elevated results in the presence of free deferoxamine. Procedures that measure TIBC by addition of excess ferric iron followed by alumina adsorption are not suitable for monitoring TIBC in acute iron overdose. The homogeneous TIBC assay can be used in acute iron overdose but underestimates TIBC when iron concentrations exceed 500 micrograms/dL (90 mumol/L). None of the methods examined are useful for measuring iron or TIBC in the presence of deferoxamine.
Assuntos
Ferro/sangue , Ferro/intoxicação , Venenos/sangue , Toxicologia/métodos , Doença Aguda , Quelantes/farmacologia , Desferroxamina/farmacologia , Overdose de Drogas , Estudos de Avaliação como Assunto , Humanos , Intoxicação/diagnóstico , Intoxicação/terapiaRESUMO
BACKGROUND: Fever and neutropenia (F&N) is a common complication of cancer chemotherapy. It is conveniently managed by hospitalization and empiric administration of parenteral antibiotics. This study attempted to determine whether pediatric cancer patients with F&N identified as low risk for morbidity and mortality by clinical criteria at the time of presentation could be treated safely as outpatients. METHODS: Seventy-three episodes of F&N in 41 patients were studied prospectively over 2 years. Eligibility criteria included age > or =2 years, reliable caretakers, and residence within 1 hour of the hospital. Exclusion criteria included hemodynamic instability, dehydration, severe mucositis, pneumonia, leukemia/lymphoma induction therapy, bone marrow transplantation, or other serious comorbidity. Patients were evaluated, received a single dose of intravenous ceftazidime, and were observed for 3-16 hours. They were randomized to receive either oral ciprofloxacin or intravenous ceftazidime as outpatients. Patients were seen daily until they had been afebrile for at least 48 hours and had a rising absolute phagocyte count of >500 cells/microL. RESULTS: Sixty-three of 73 episodes (86%) were successfully managed on an outpatient basis. For 31 of 33 episodes in the ceftazidime arm, the patients remained outpatients, compared with 32 of 40 in the ciprofloxacin arm; this difference was not statistically significant. On average, patients remained febrile for 2.7 days and were treated for 4.7 days. Seventy-seven percent of episodes required no modification of initial antibiotic therapy. Of the 10 patients who were hospitalized, 4 had prolonged fever and 3 had emesis. Protracted neutropenia was associated with the need for hospitalization. There were no deaths, intensive care unit transfers, or serious complications. CONCLUSIONS: Carefully selected low risk children with fever and neutropenia can be treated safely as outpatients. Close daily medical scrutiny is required.
Assuntos
Assistência Ambulatorial , Antineoplásicos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Febre/tratamento farmacológico , Neutropenia/tratamento farmacológico , Adolescente , Infecções Bacterianas/etiologia , Ceftazidima/uso terapêutico , Cefalosporinas/uso terapêutico , Criança , Pré-Escolar , Ciprofloxacina/uso terapêutico , Feminino , Febre/induzido quimicamente , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Estudos Prospectivos , Medição de RiscoRESUMO
A 1177 bp cDNA fragment encoding the human milk protein beta-casein was introduced into Solanum tuberosum cells under control of the auxin-inducible, bidirectional mannopine synthase (mas1',2') promoters using Agrobacterium tumefaciens-mediated leaf disc transformation methods. Antibiotic-resistant plants were regenerated and transformants selected based on luciferase activity carried by the expression vector containing the human beta-casein cDNA. The presence of human beta-casein cDNA in the plant genome was detected by PCR and DNA hybridization experiments. Human beta-casein mRNA was identified in leaf tissues of transgenic plants by RT-PCR analysis. Human beta-casein was identified in auxin-induced leaf and tuber tissues of transformed potato plants by immunoprecipitation and immunoblot analysis. Human beta-casein produced in transgenic plants migrated in polyacrylamide gels as a single band with an approximate molecular mass of 30 kDa. Immunoblot experiments identified approximately 0.01% of the total soluble protein of transgenic potato leaf tissue as beta-casein. The above experiments demonstrate the expression of human milk beta-casein as part of an edible food plant. These findings open the way for reconstitution of human milk in edible plants for replacement of bovine milk in baby foods for general improvement of infant nutrition, and for prevention of gastric and intestinal diseases in children.
Assuntos
Caseínas/genética , Caseínas/metabolismo , Proteínas Recombinantes/genética , Solanum tuberosum/genética , Caseínas/imunologia , Clonagem Molecular , Vetores Genéticos/genética , Humanos , Plantas Geneticamente Modificadas/genética , Proto-Oncogene Mas , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Transformação GenéticaRESUMO
We determined the cost of allogeneic packed red blood cells and autologous whole blood donated either preoperatively or in the operating room during hemodilution. Direct and indirect cost estimates were based on patients requiring simple transfusion and included procurement and preparation of the blood including testing performed, materials and time used, waste, and materials for administration. Data were derived from prospective blood bank time studies, material invoice records, and retrospective review of anesthesia times. Viral infection and transfusion reaction costs were accepted from previously published sources. Direct cost of purchasing and indirect costs of preparation resulted in an overall cost of $107.26 for the first unit of allogeneic packed red blood cells transfused. A second unit was slightly less costly ($100.89), as no type and screen was required and the same delivery set and filter can be used. The total cost of acquisition, processing, and transfusion of 1 U of preoperatively donated autologous blood was $97.83. The total cost of a 2-U transfusion of autologous whole blood donated in the operating room during acute normovolemic hemodilution was $83.10. These data suggest that autologous predonation of whole blood is somewhat less expensive than allogeneic packed red blood cells, and that hemodilution may be a cost effective alternative to autologous predonation in selected patients.
Assuntos
Transfusão de Sangue Autóloga/economia , Transfusão de Eritrócitos/economia , Custos de Cuidados de Saúde , HumanosRESUMO
14C-deoxyglucose autoradiographs of attack rats were compared densitometrically with those of control rats whose electrodes were located nearby and elicited nonaggressive behaviors like those that accompanied the attack. Most closely associated with attack was the path from the ventromedial hypothalamus through the ventral supraoptic commissural pathway to the peripeduncular area, subparafascicular nucleus, zona incerta, and cuneiform area. Moderately correlated with attack were 4 visual areas: the dorsal and ventral lateral geniculate nuclei, pretectal area, and superior colliculus. Activity in the periaqueductal gray was unrelated to attack ipsilaterally and only weakly related contralaterally. In an orthogonal analysis, upward-oriented flight thresholds were significantly correlated with medial activation extending anteriorly to the lateral septal nucleus, dorsally to the thalamic paraventricular-parataenial region, and posteriorly to the periaqueductal gray.
Assuntos
Agressão/fisiologia , Aprendizagem da Esquiva/fisiologia , Hipotálamo/fisiologia , Animais , Mapeamento Encefálico , Estimulação Elétrica , Masculino , RatosRESUMO
Postoperative ileus following gynecologic surgery can prolong hospitalization and may predispose patients to mechanical obstruction. Our objective was to study the safety and efficacy of a water-soluble, hyperosmolar, radiocontrast material in the management of postoperative ileus in patients having gynecologic surgery. Of 115 cases, 57 were studied prospectively and received water-soluble radio-opaque contrast material via a nasogastric tube if bowel function had not returned by the third day. Fifty-eight well-matched control cases were managed without this material and received a suppository on the third day. The contrast material was well tolerated. Return of bowel function, day of oral intake, subsequent postoperative recovery, and duration of hospital stay were similar in the two groups. Water-soluble, hyperosmolar, radio-opaque contrast material given on the third postoperative day was safe, but of no apparent clinical benefit in resolving ileus following gynecologic surgery.
Assuntos
Meios de Contraste/uso terapêutico , Diatrizoato/uso terapêutico , Histerectomia , Obstrução Intestinal/terapia , Ovariectomia , Complicações Pós-Operatórias/terapia , Apendicectomia , Feminino , Humanos , Obstrução Intestinal/etiologia , Concentração Osmolar , Neoplasias Ovarianas/cirurgia , Estudos Prospectivos , Salpingostomia , Solubilidade , Aderências Teciduais , Neoplasias do Colo do Útero/cirurgia , ÁguaRESUMO
BACKGROUND: Balloon angioplasty of atherosclerotic arteries results in activation of the coagulation cascade. Several coagulation factors, including factor Xa and thrombin, are mitogenic for vascular smooth muscle cells in vitro and thus may play a role in restenosis after balloon angioplasty. Specific inhibition of factor Xa can be achieved with recombinant antistasin (rATS) or tick anticoagulant peptide (rTAP). We hypothesized that inhibition of Xa would limit restenosis after balloon angioplasty in an atherosclerotic rabbit model. METHODS AND RESULTS: Focal femoral atherosclerosis was induced by air desiccation injury and a high-cholesterol diet in 38 New Zealand White rabbits. Recombinant antistasin (n = 20 arteries) or rTAP (n = 14 arteries) was administered by intravenous bolus at the time of balloon angioplasty and followed by a 2-hour infusion; controls (n = 21 arteries) received bolus heparin alone (150 U/kg). Therapeutic prolongation of the activated partial thromboplastin time occurred, and antithrombotic drug levels were achieved in all animals. Luminal diameter in millimeters by quantitative angiography did not differ between treatment groups before (1.1 +/- 0.2 for controls, 1.1 +/- 0.2 for rATS, and 1.1 +/- 0.3 for rTAP) or after balloon angioplasty (1.5 +/- 0.3 for controls, 1.4 +/- 0.2 for rATS, and 1.4 +/- 0.2 for rTAP). At 28 days, treatment with factor Xa inhibitors tended to result in arteries with larger luminal diameter than controls (1.2 +/- 0.3 for rATS, 1.2 +/- 0.3 for rTAP versus 1.0 +/- 0.3 for control, P = .09 by one-way ANOVA). Restenosis, defined as reduction in angiographic luminal diameter (in mm) from 2 hours after angioplasty to 28 days after angioplasty was less in the rATS group than in controls (-0.2 +/- 0.1 versus -0.5 +/- 0.4, P < .001) and tended to be less in the rTAP group (-0.3 +/- 0.2 versus -0.5 +/- 0.4, P = .07). Quantitative histopathological analysis showed less percent cross-sectional area narrowing by plaque in both rATS- and rTAP-treated arteries compared with controls (42 +/- 21%, 47 +/- 18%, and 63 +/- 14%, respectively; P < .01 by one-way ANOVA). CONCLUSIONS: We conclude that a 2-hour infusion of rATS or rTAP reduced angiographic restenosis and resulted in less luminal cross-sectional narrowing by plaque compared with controls.
Assuntos
Angioplastia com Balão , Arteriosclerose/terapia , Inibidores do Fator Xa , Artéria Femoral , Hormônios de Invertebrado/uso terapêutico , Peptídeos/uso terapêutico , Animais , Arteriosclerose/diagnóstico por imagem , Proteínas de Artrópodes , Peptídeos e Proteínas de Sinalização Intercelular , Sanguessugas , Masculino , Coelhos , Radiografia , Recidiva , Carrapatos , Fatores de TempoRESUMO
Photodynamic therapy, the light activation of photosensitizers into cytotoxic mediators, has been a successful treatment for experimental intimal hyperplasia (IH). To understand the basis of the photosensitizer chloroaluminum sulfonated phthalocyanine (CASPc)-mediated photoinhibition of intimal hyperplasia in the rat common carotid artery model, we studied photosensitizer partitioning in hyperplastic as compared to normal arterial tissue. Serum clearance of CASPc is exponential with, a half-life of 300 minutes. Laser-induced fluorescence and spectrofluorimetric analyses of artery tissue demonstrated an approximately 60% lower uptake and retention of CASPc by normal arterial tissue as compared to arteries with IH; the differences become more pronounced at 24 h. Fluorescent microscopy of arterial tissue demonstrated increased uptake of the CASPc by the artery with IH. However, by 24 h it is primarily the IH tissue that has retained the CASPc, with clearance of the dye from the media of normal or hyperplastic arteries. These data demonstrate that IH, like neoplastic tissue, has an increased accumulation of CASPc compared to normal artery. The preferential partitioning into hyperplastic tissue has implications for therapeutic targeting of this cellular population with photodynamic therapy.
Assuntos
Artérias/química , Artérias/patologia , Indóis/análise , Compostos Organometálicos/análise , Fototerapia , Radiossensibilizantes/uso terapêutico , Animais , Artérias/metabolismo , Artéria Carótida Primitiva/química , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , DNA/análise , DNA/genética , Meia-Vida , Hiperplasia/radioterapia , Indóis/sangue , Lasers , Masculino , Microscopia de Fluorescência , Compostos Organometálicos/sangue , Ratos , Ratos Sprague-Dawley , Túnica Íntima/química , Túnica Íntima/metabolismo , Túnica Íntima/patologiaRESUMO
We have recently described extensive inhibitory interactions between inputs to the ventroposterolateral (VPL) (Roberts and Wells 1990, 1991) and ventroposteromedial (VPM) (Salt 1989) portions of the ventrobasal nucleus of the thalamus (VB). We wished to determine whether (i) the inhibition observed in the VPL was operating at the thalamic level, (ii) was dependent on GABA receptors, (iii) was demonstrable on neurons of the ventro-posteromedial nucleus of the thalamus (VPM) and (iv) was operant on test responses evoked by natural stimuli. Conditioning stimulation of sciatic nerve afferents caused inhibition of air jet evoked test responses of single VB neurons in urethane-anaesthetized rats. Both VPM and VPL neurons were subject to inhibition by conditioning stimulation of hindlimb afferents, indicating the wide-spread nature of the inhibitory process. This inhibition was reduced by the iontophoretic application of SR95531, a GABAA receptor antagonist. We conclude that there is a widely distributed inhibitory system operating in the somatic thalamus which involves both the medial and lateral portions of the nucleus and is, at least in part, mediated by GABAA receptors. The possible involvement of inhibitory processes and intrinsic membrane properties of thalamic neurones in the somatotopic plasticity of the sensory thalamus following deafferentation and in deafferentation pain is discussed.
Assuntos
Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios Aferentes/fisiologia , Dor/fisiopatologia , Tálamo/fisiopatologia , Ácido gama-Aminobutírico/fisiologia , Animais , Condicionamento Operante/fisiologia , Antagonistas GABAérgicos , Antagonistas de Receptores de GABA-A , Membro Posterior/inervação , Iontoforese , Estimulação Física , Piridazinas/farmacologia , Ratos , Ratos Endogâmicos , Vibrissas/fisiologiaAssuntos
Valva Aórtica , Bioprótese , Cálcio/metabolismo , Próteses Valvulares Cardíacas , Idoso , Animais , Valva Aórtica/patologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/terapia , Calcinose/metabolismo , Calcinose/patologia , Ecocardiografia Doppler , Feminino , Humanos , SuínosRESUMO
The effect of photodynamic therapy on the tumor microvasculature in the first few hours after treatment was studied at the light and electron microscopy levels. BALB/c mice with EMT-6 tumor received ip injections of hematoporphyrin derivative, chlorin, or phthalocyanine, and 24 hours later, the tumors were treated with light at 100 J/cm2 at the appropriate therapeutic wavelength for each photosensitizer. Animals were killed and their tumors removed at time 0, 30 minutes, 1 hour, and 2, 4, 6, 8, 12, 16, and 24 hours after treatment. The results indicate that for all three sensitizers the effects of photodynamic therapy leading to rapid necrosis of tumor tissue are not the result of direct tumor cell kill but are secondary to destruction of the tumor microvasculature. The first observable signs of destruction occur in the subendothelial zone of the tumor capillary wall. This zone, composed of dense collagen fibers and other connective tissue elements, is destroyed in the first few hours after phototherapy. However, the ultrastructural changes seen in this zone are different for the hematoporphyrin derivative, compared with chlorin and phthalocyanine. Binding of photosensitizers to the elements in this zone as well as altered permeability and transport through the endothelial cell layer because of the increased intraluminal pressure may be key features of tumor destruction.
Assuntos
Fotorradiação com Hematoporfirina , Hematoporfirinas/farmacologia , Indóis/farmacologia , Neoplasias Mamárias Experimentais/ultraestrutura , Fotoquimioterapia , Porfirinas/farmacologia , Animais , Feminino , Derivado da Hematoporfirina , Isoindóis , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Microcirculação/ultraestruturaRESUMO
The glycoinositol phospholipid membrane anchor of human erythrocyte acetylcholinesterase (EC 3.1.1.7) is composed of a glycan linked through a glucosamine residue to an inositol phospholipid that is resistant to the action of phosphatidylinositol-specific phospholipase C. Deamination cleavage of the glucosamine with nitrous acid released the inositol phospholipid which was purified by high performance liquid chromatography. Analysis by fast atom bombardment mass spectrometry with negative ion monitoring and by the complementary technique of collision-induced dissociation revealed molecular and daughter ions that indicated a plasmanylinositol with a palmitoyl group on an inositol hydroxyl. The intact membrane anchor was released from reductively methylated human erythrocyte acetylcholinesterase by proteolysis with papain or Pronase, deacylated by base hydrolysis, and purified by high performance liquid chromatography. Positive and negative ion fast atom bombardment mass spectrometry of the major products isolated by high performance liquid chromatography indicated the following structure for the complete glycoinositol phospholipid anchor. (formula; see text) Methylation of free amino groups by reduction with deuterium instead of hydrogen permitted determination of the number of free amino groups in individual fragment ions as further confirmation of structural assignments. The structure of the glycan portion of the human erythrocyte acetylcholinesterase membrane anchor appears to be similar to that described for Trypanosome brucei variant surface glycoprotein MITat 1.4 (variant 117) (Ferguson, M.A.J., Homans, S.W., Dwek, R.A., and Rademacher, T.W. (1988) Science 239, 753-759) except for the absence of a galactose antenna and the presence of a phosphorylethanolamine on the hexose adjacent to glucosamine.
Assuntos
Acetilcolinesterase/sangue , Eritrócitos/enzimologia , Glicolipídeos/isolamento & purificação , Lipídeos de Membrana/análise , Fosfatidilinositóis/isolamento & purificação , Plasmalogênios/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Glucosamina/metabolismo , Glicosilfosfatidilinositóis , Humanos , Espectrometria de Massas , Ácido Nitroso , Papaína , PronaseRESUMO
Therapeutic gain factors (TGFs) have been determined for three spontaneous tumors of the C3H mouse treated by photons + normobaric oxygen (O2(1) ATA), photons + hyperbaric oxygen (O2 3 ATA), photons + misonidazole, or fast neutrons. The tumors were early generation isotransplants of spontaneous tumors: MCaIV, a mammary carcinoma; FSaII, a fibrosarcoma; and SCCVII, a squamous cell carcinoma. The tumors, transplanted to the right leg, were 6 mm at start of treatment. Normal tissue responses studied were acute reaction of normal skin (all treatment modalities) and LD50 following irradiation of the upper abdomen (in test of photons + O2 at 1 or 3 ATA). Thus both the tumor and normal tissues would be classified as "acute responding." All subject tissues were at congruent to 34.5-35 degrees C at irradiation. Treatments were based on d(25)Be or p(43)Be fast neutron beams, 60Co and 137Cs photon beams. Treatments were given in 5 or 15 equal doses in 5 days. For photon treatments, TGFs (air/O2 3 ATA) were substantially and significantly larger than 1 for all three tumor systems treated at small or large doses per fraction when related to skin or abdominal tissue responses. The TGFs (air/O2 1 ATA) were greater than 1 at small doses per fraction for MCaIV and FSaII for skin as the normal tissue; the TGFs for all three tumors and at all doses per fraction would be greater than 1 when related to upper abdominal tissues. TGFs (O2 1 ATA/O2 3 ATA) for photon irradiation greater than 1 were found only for SCCVII and that obtained for both large and small doses per fraction. Misonidazole achieved impressive TGFs (air/air + miso or air/O2 1 ATA + miso); the drug was tested only at 10-12 Gy/fraction and relative to skin. RBEs(FN) for the three tumors were lower at 1.5-2 Gy(FN)/fraction than at 5-6 Gy(FN)/fraction, i.e. the opposite to that reported for normal tissue (RBE increases with decreasing dose per fraction). A TGF (relative to skin reaction) greater than 1 for fast neutron therapy was found only for SCCVII when treated at large doses/fraction; this was true for air or O2 1 ATA conditions.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Fibrossarcoma/radioterapia , Neoplasias Mamárias Experimentais/radioterapia , Animais , Terapia Combinada , Nêutrons Rápidos , Feminino , Oxigenoterapia Hiperbárica , Masculino , Camundongos , Camundongos Endogâmicos C3H , Misonidazol/uso terapêutico , Transplante de Neoplasias , Oxigênio/uso terapêutico , Dosagem RadioterapêuticaRESUMO
We reviewed colonoscopic biopsies of the lower gastrointestinal tract performed during a two-year period. Those representing neoplasia were excluded. Formalin-fixed paraffin-embedded biopsy specimens from 53 patients were studied by in situ DNA hybridization for cytomegalovirus (CMV) using commercially available biotinylated DNA probes detected by an avidin-biotin peroxidase technique. Nine of the patients were severely immunocompromised: four had acquired immunodeficiency syndrome, three had ulcerative colitis and were receiving high-dose steroid therapy, one was a bone marrow transplant recipient, and one had idiopathic pulmonary fibrosis and was receiving therapy with prednisone and cyclophosphamide. Four of these had evidence of CMV infection by routine histology and DNA hybridization. Three additional immunocompromised patients had evidence of CMV infection by DNA hybridization alone. Forty-four patients had inflammatory conditions or ulcerations of the lower gastrointestinal tract. Six of these had evidence of CMV by DNA hybridization alone. Histologically normal as well as enlarged and cytomegalic cells were probe positive, and the cells were sparse to numerous in number. They were found in the epithelium and/or lamina propria. This technique was demonstrated to be applicable to routinely processed colonic biopsy specimens.