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2.
J Geophys Res Atmos ; 122(19): 10510-10538, 2017 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33006328

RESUMO

Transport is a key parameter in air quality research and plays a dominant role in the Colorado Northern Front Range Metropolitan Area (NFRMA), where terrain induced flows and recirculation patterns can lead to vigorous mixing of different emission sources. To assess different transport processes and their connection to air quality in the NFRMA during the FRAPPÉ and DISCOVER-AQ campaigns in summer 2014, we use the Weather Research and Forecasting Model with inert tracers. Overall, the model represents well the measured winds and the inert tracers are in good agreement with observations of comparable trace gas concentrations. The model tracers support the analysis of surface wind and ozone measurements and allow for the analysis of transport patterns and interactions of emissions. A main focus of this study is on characterizing pollution transport from the NFRMA to the mountains by mountain-valley flows and the potential for recirculating pollution back into the NFRMA. One such event on 12 August 2014 was well captured by the aircraft and is studied in more detail. The model represents the flow conditions and demonstrates that during upslope events, frequently there is a separation of air masses that are heavily influenced by oil and gas emissions to the North and dominated by urban emissions to the South. This case study provides evidence that NFRMA pollution not only can impact the nearby Foothills and mountain areas to the East of the Continental Divide, but that pollution can "spill over" into the valleys to the West of the Continental Divide.

3.
Dev Comp Immunol ; 58: 119-28, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26592965

RESUMO

Haematopoiesis is a process that is responsible for generating sufficient numbers of blood cells in the circulation and in tissues. It is central to maintenance of homeostasis within an animal, and is critical for defense against infection. While haematopoiesis is common to all animals possessing a circulatory system, the specific mechanisms and ultimate products of haematopoietic events vary greatly. Our understanding of this process in non-vertebrate organisms is primarily derived from those species that serve as developmental and immunological models, with sparse investigations having been carried out in other organisms spanning the metazoa. As research into the regulation of immune and blood cell development advances, we have begun to gain insight into haematopoietic events in a wider array of animals, including the molluscs. What began in the early 1900's as observational studies on the morphological characteristics of circulating immune cells has now advanced to mechanistic investigations of the cytokines, growth factors, receptors, signalling pathways, and patterns of gene expression that regulate molluscan haemocyte development. Emerging is a picture of an incredible diversity of developmental processes and outcomes that parallels the biological diversity observed within the different classes of the phylum Mollusca. However, our understanding of haematopoiesis in molluscs stems primarily from the three most-studied classes, the Gastropoda, Cephalopoda and Bivalvia. While these represent perhaps the molluscs of greatest economic and medical importance, the fact that our information is limited to only 3 of the 9 extant classes in the phylum highlights the need for further investigation in this area. In this review, we summarize the existing literature that defines haematopoiesis and its products in gastropods, cephalopods and bivalves.


Assuntos
Hematopoese , Hemócitos/fisiologia , Animais , Humanos , Imunidade Inata , Mitose , Moluscos , Fagocitose
4.
Int J Obstet Anesth ; 21(3): 212-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22632744

RESUMO

BACKGROUND: Magnesium has been reported to augment the analgesic effects of opioids when co-administered into the cerebrospinal fluid. The purpose of this study was to determine the influence of intravenous magnesium therapy administered for preeclampsia on the duration of intrathecal fentanyl analgesia for labor. METHODS: Thirty-four nulliparous parturients having labor induced for preeclampsia and receiving intravenous magnesium therapy were recruited. Thirty-four nulliparous patients having labor induced for elective or medical reasons were recruited as controls. At request for analgesia, baseline serum magnesium levels were obtained and combined spinal-epidural analgesia was initiated with intrathecal fentanyl 25µg. Before injection of fentanyl, a sample of cerebrospinal fluid was obtained for magnesium assay. An epidural catheter was sited but no additional medications were administered until the second request for analgesia. The primary outcome was duration of intrathecal fentanyl analgesia. RESULTS: There was no difference in the median duration of analgesia between the magnesium [79min (95% CI 76 to 82)] and control groups [69min (95% CI 56 to 82)] (difference between medians: 10min (95% CI -4 to 21min; P=0.16). There was neither a relationship between the serum and cerebrospinal fluid magnesium concentrations nor the cerebrospinal magnesium concentration and duration of intrathecal fentanyl analgesia. CONCLUSIONS: Intravenous magnesium therapy at doses typically used for seizure prophylaxis in preeclampsia did not influence the duration of intrathecal fentanyl labor analgesia. However, this study may have been underpowered to detect a difference and future study is warranted.


Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Magnésio/administração & dosagem , Adulto , Feminino , Humanos , Injeções Intravenosas , Magnésio/análise , Gravidez , Fatores de Tempo
6.
Int J Obstet Anesth ; 19(2): 223-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20194012

RESUMO

We describe the use of epidural analgesia in a 39-year-old G2P1 parturient presenting at 38(+6) weeks estimated gestation with confirmed influenza A H1N1 and superimposed bilateral pneumonia. Although the patient had an uncomplicated intra- and post-partum course, little is known about the safety of performing neuraxial analgesia or anesthesia in patients with influenza. The prevalence of viremia and possible translocation of blood-borne virus to the central nervous system are discussed.


Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Obesidade/complicações , Complicações Infecciosas na Gravidez , Adulto , Feminino , Humanos , Gravidez , Resultado do Tratamento
7.
Int J Obstet Anesth ; 18(4): 328-34, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19682886

RESUMO

BACKGROUND: Improving the success of external cephalic version (ECV) for breech presentation may help avoid some cesarean deliveries. The results of randomized trials comparing the success of ECV with neuraxial analgesia compared to control are inconsistent. We hypothesized that combined spinal-epidural (CSE) analgesia would increase the success of ECV when compared with systemic opioid analgesia. METHODS: Parturients with singleton breech presentation (n=96) were randomized to receive CSE analgesia with bupivacaine 2.5mg and fentanyl 15 microg (CSE group) or intravenous fentanyl 50 microg (SYS group) before ECV attempt. The primary outcome was ECV success. RESULTS: The success rate of ECV was 47% with CSE and 31% in the SYS group (P=0.14). Subsequent vaginal delivery was 36% for CSE and 25% for SYS (P=0.27). Median [IQR] visual analog pain scores (0-100mm scale) were lower with CSE (3 [0-12]) compared to SYS analgesia (36 [16 to 54]) (P<0.005) and patient satisfaction (0-10 scale) was higher (CSE 10 [9 to 10] versus SYS 7 [4 to 9]) (P<0.005). There were no differences in fetal heart rate patterns, but median time to return to fetal heart rate reactivity after analgesia was shorter with CSE (13 [IQR 9-21] min) compared to the SYS group (39 [IQR 23-51] min) (P=0.02). CONCLUSIONS: There was no difference in the rate of successful ECV or vaginal delivery with CSE compared to intravenous fentanyl analgesia. Pain scores were lower and satisfaction higher with CSE analgesia, and median time to fetal heart rate reactivity was shorter in the CSE group.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Raquianestesia , Apresentação Pélvica/terapia , Versão Fetal , Adulto , Parto Obstétrico , Feminino , Hemodinâmica/fisiologia , Humanos , Recém-Nascido , Medição da Dor , Náusea e Vômito Pós-Operatórios/epidemiologia , Gravidez , Tamanho da Amostra , Resultado do Tratamento
8.
Animal ; 3(1): 24-31, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22444169

RESUMO

An experiment (3 × 4 factorial arrangement) was conducted to investigate the interaction between different levels of lactose (60 v. 150 v. 250 g/kg) and seaweed extract (0 v. 1 v. 2 v. 4 g/kg) containing both laminarin and fucoidan derived from Laminaria spp. on growth performance and nutrient digestibility of weanling pigs. In all, 384 piglets (24 days of age, 7.5 kg (s.d. 1 kg) live weight) were blocked on the basis of live weight and were assigned to one of 12 dietary treatments (eight replicates per treatment). Piglets were offered diets containing either low (60 g/kg), medium (150 g/kg) or high (250 g/kg) lactose levels with one of the following levels of seaweed extract additive: (1) 0 g/kg, (2) 1 g/kg, (3) 2 g/kg or (4) 4 g/kg seaweed extract. The pigs were offered the diets ad libitum for 21 days post weaning. There was a significant lactose × seaweed extract interaction (P < 0.05) in average daily gain (ADG) during the experimental period (days 0 to 21). At the low and medium levels of lactose, there was an increase in ADG as the level of seaweed extract increased to 2 g/kg (P < 0.05). However, at the high level of lactose there was no further response in ADG as the level of seaweed extract increased above 1 g/kg. There was a significant lactose × seaweed extract interaction during the experimental period (days 0 to 21) (P < 0.05) on the food conversion ratio (FCR). At the low level of lactose, there was a significant improvement in FCR as the levels of seaweed extract increased to 4 g/kg (P < 0.01). At the medium level of lactose, there was a significant improvement in FCR as seaweed extract increased to 2 g/kg. However, there was no significant effect of seaweed extract on FCR at the high levels of lactose (P > 0.05). There was a linear increase in average daily feed intake (ADFI) during the experimental period (days 0 to 21) (P < 0.05) as levels of seaweed extract increased. There was a linear increase in ash digestibility (P < 0.01) during the experimental period (days 0 to 21) as the level of lactose increased. There was a quadratic decrease (P < 0.01) in nitrogen (N) and neutral detergent fibre digestibility as the levels of lactose increased. In conclusion, pigs responded differently to the inclusion levels of seaweed extract at each level of lactose supplementation. The inclusion of a laminarin-fucoidan extract in piglet diets may alleviate the use for high-lactose diets (>60 g/kg) and would also alleviate some of the common problems that occur post weaning.

10.
Animal ; 2(10): 1465-73, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22443904

RESUMO

An experiment (complete randomised design) was conducted to investigate the effects of Laminaria hyperborea and Laminaria digitata seaweed extract inclusion on gut morphology, selected intestinal microbiota populations, volatile fatty acid concentrations and the immune status of the weaned pig. Twenty-eight piglets (24 days of age, 6.5 ± 1.4 kg live weight) were assigned to one of four dietary treatments for 7 days and then sacrificed: (T1) basal diet (control); (T2) basal diet and 1.5 g/kg L. hyperborea seaweed extract; (T3) basal diet and 1.5 g/kg L. digitata seaweed extract; and (T4) basal diet and 1.5 g/kg of a combination of L. hyperborea and L. digitata seaweed extract. The seaweed extract contained both laminarin and fucoidan. Digesta samples were taken from the caecum and colon to measure the enterobacteria, bifidobacteria and lactobacilli populations and for volatile fatty acid analysis. Tissue samples were taken from the duodenum, jejunum and ileum for morphological examination. Blood samples were taken to determine the cytokine gene expression profile and to measure the phagocytotic capacity of the blood. Pigs offered diets containing L. hyperborea seaweed extract had less bifidobacteria in the colon (P < 0.05) and lactobacilli in the caecum (P < 0.05) and colon (P < 0.001). The inclusion of L. digitata seaweed extract resulted in lower populations of enterobacteria in the caecum and colon (P < 0.01), bifidobacteria in the caecum (P < 0.05), and lactobacilli in the caecum (P < 0.05) and colon (P < 0.001). Pigs offered the combination of L. hyperborea and L. digitata seaweed extracts had less enterobacteria (P < 0.05) and lactobacilli (P < 0.01) in the caecum and colon. Pigs offered the L. digitata-supplemented diet had a reduced villous height in the duodenum and jejunum (P < 0.05). The inclusion of the L. digitata seaweed extract increased the molar proportion of butyric acid in the colon (P < 0.05). There was a significant reduction in the ammonia concentration in the colon with the inclusion of L. hyperborea (P < 0.01) and L. digitata (P < 0.05) seaweed extracts. An increase in the expression of the Interleukin-8 mRNA was observed on day 6 with the supplementation of the combination of L. hyperborea and L. digitata seaweed extract (P < 0.05). The inclusion of L. hyperborea seaweed extract resulted in an increase in total monocyte number (P < 0.05). In conclusion, the supplementation of L. hyperborea and L. digitata seaweed extract alone and in combination reduced the enterobacteria, bifidobacteria and lactobacilli populations in the caecum and colon, while only marginal effects on the immune response was observed.

11.
J Clin Pharmacol ; 46(12): 1460-8, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17101745

RESUMO

Palifermin (deltaN23KGF) decreases the incidence, severity, and duration of oral mucositis. The objectives of this open-label study were to evaluate the pharmacokinetics of single-dose palifermin in subjects with varying degrees of renal function. A single 90-mcg/kg intravenous dose of palifermin was administered to 31 subjects with varying levels of renal function (normal to requiring hemodialysis). Pharmacokinetic analyses were conducted using serum palifermin concentrations. There was considerable overlap in mean palifermin serum clearance among the groups, ranging from 318 to 495 mL/h/kg, indicating that the level of renal function did not affect clearance in humans; thus, no dose adjustment of palifermin is indicated for patients with renal dysfunction.


Assuntos
Fator 7 de Crescimento de Fibroblastos/farmacocinética , Rim/fisiologia , Adulto , Idoso , Área Sob a Curva , Fadiga/induzido quimicamente , Feminino , Fator 7 de Crescimento de Fibroblastos/administração & dosagem , Fator 7 de Crescimento de Fibroblastos/efeitos adversos , Meia-Vida , Cefaleia/induzido quimicamente , Humanos , Injeções Intravenosas , Rim/fisiopatologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Testes de Função Renal , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Boca/efeitos dos fármacos , Boca/patologia , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologia , Índice de Gravidade de Doença , Lesões dos Tecidos Moles/induzido quimicamente , Estomatite/induzido quimicamente
12.
Diabetologia ; 44(11): 2018-24, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11719833

RESUMO

AIMS/HYPOTHESIS: To study the effects of a specific glucagon receptor antagonist (Bay 27-9955), on plasma glucose concentrations and rates of glucose production in response to hyperglucagonaemia in humans. METHODS: The study was conducted as a two-dose [Low Dose Bay 27-9955 70 mg, (n = 6), High Dose Bay 27-9955 200 mg, (n = 8)], double blind, placebo controlled, crossover study. Basal glucose production was measured after an overnight fast with [6,6-2H]. At 0 min Bay 27-9955 or placebo was administered and at 120 min an infusion of somatostatin [0.1 microg x (kg x min)(-1)], insulin [24 pmol x (m2 x min)(-1)] and glucagon [3 ng x (kg x min)(-1)] was initiated. RESULTS: Basal plasma glucose concentrations were about 5 mmol/l and basal rates of glucose production were about 13 micromol x (kg x min)(-1). During the hyperglucagonaemic period, plasma glucagon concentrations doubled to 100 pg/ml, plasma glucose concentration increased by 75 % to a peak of about 10 mmol/l and glucose production doubled to about 23 micromol x (kg x min)(-1) (p < 0.0001 vs basal). In the High Dose Group these effects of glucagon were markedly blunted, plasma glucose concentrations were 7.6 +/- 1.1 mmol/l (p = 0.012 vs placebo) and rates of glucose production increased minimally to 15.3 +/- 1.9 micromol x (kg-min)(-1) (p < 0.0003 vs placebo]. In the Low Dose Group, there was a proportional decrease in the effects of Bay 27-9955 on these parameters. CONCLUSION/INTERPRETATION: Bay 27-9955 is an effective and safe glucagon antagonist in humans. Given the potentially important role of glucagon in increasing glucose production and gluconeogenesis in patients with Type II (non-insulin-dependent) diabetes mellitus this agent could represent an innovative class of therapeutic agents for the disease.


Assuntos
Compostos de Bifenilo/farmacologia , Glicemia/metabolismo , Glucagon/farmacologia , Antagonistas de Hormônios/farmacologia , Receptores de Glucagon/antagonistas & inibidores , Adulto , Compostos de Bifenilo/farmacocinética , Glicemia/efeitos dos fármacos , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Antagonistas de Hormônios/farmacocinética , Humanos , Insulina/sangue , Cinética , Masculino , Placebos , Valores de Referência , Somatostatina/farmacologia , Fatores de Tempo
13.
Dev Comp Immunol ; 25(7): 561-4, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11472778

RESUMO

We examined a potential mechanism for adoptively transferred resistance against Schistosoma mansoni in schistosome-susceptible snails receiving allografts of the hematopoietic amebocyte-producing organ (APO) from a schistosome-resistant strain of Biomphalaria glabrata. Susceptible NIH albino snails first were implanted with the APO from resistant Salvador strain donors. At 14 days post-implantation, cell-free plasma was isolated from APO recipients and injected into a second group of NIH albino snails. Controls were injected with plasma from NIH albino snails that previously had received implants of Salvador mantle, an immunologically inert tissue. Finally, plasma recipients, along with untampered (non-injected) controls, were exposed to miracidia of S. mansoni and subsequently monitored for infection. A significantly lower prevalence of infection occurred in the group injected with plasma from APO recipients (53%) in comparison with that in untampered controls (100%) or in snails receiving plasma from mantle recipients (97%). These results suggest that adoptively transferred resistance in B. glabrata results from secretion of soluble resistance factor(s) by the implant, rather than, or in addition to, formation of a hemocyte chimera having cytotoxic donor hemocytes.


Assuntos
Transferência Adotiva , Anticorpos Anti-Helmínticos/biossíntese , Biomphalaria/imunologia , Transplante de Células-Tronco Hematopoéticas , Schistosoma mansoni/imunologia , Animais , Formação de Anticorpos
14.
Clin Pharmacokinet ; 40 Suppl 1: 11-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11352437

RESUMO

OBJECTIVE: Moxifloxacin is a new 8-methoxyfluoroquinolone with a broad antibacterial spectrum. The purpose of the present study was to determine the effects of age and gender on pharmacokinetics, surrogate pharmacodynamics, safety and tolerability of a single dose of moxifloxacin. DESIGN: This was a randomised, double-blind, placebo-controlled, parallel-group single dose trial in young and elderly healthy volunteers. PATIENTS AND PARTICIPANTS: The study included 36 volunteers in 3 age and gender groups: young males (mean age 32 years), elderly males (mean age 74 years), and elderly females (mean age 74 years). METHODS: Participants received either a single 200mg oral dose of moxifloxacin (8/group) or placebo (4/group). Blood samples for moxifloxacin pharmacokinetics were obtained before and up to 48 hours after administration. Urine samples were collected for pharmacokinetics, and volunteers were monitored for clinical adverse events and laboratory abnormalities. RESULTS: Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were higher in elderly females than in elderly males; however, when normalised for bodyweight, these pharmacokinetic parameters were not significantly different between the groups. Moreover, the plasma pharmacokinetics in elderly males were not meaningfully different from those in young males. Elimination half-life averaged 12 to 13 hours for the 3 groups. Surrogate pharmacodynamic measures were derived using AUC/MIC (minimal inhibitory concentration) and Cmax/MIC ratios. These assessments indicated that, given the linear pharmacokinetics of moxifloxacin previously demonstrated, a dose of 400mg would produce mean Cmax/MIC values in the different subgroups ranging from 10.4 to 15.4 for an MIC of 0.25, and 20.8 to 30.8 for an MIC of 0.125. The corresponding ranges of projected AUC/MIC ratios would be 112 to 158 for an MIC of 0.25, and 224 to 314 for an MIC of 0.125. The accepted target values of AUC/MIC and Cmax/MIC for quinolones are 125 and 10, respectively. There were no serious adverse events or differences in adverse event profiles between the groups. CONCLUSIONS: Moxifloxacin does not exhibit age- or gender-dependent pharmacokinetics. Oral doses of 200 to 400mg yield effective antibacterial concentrations on the first day of administration.


Assuntos
Anti-Infecciosos/farmacocinética , Compostos Aza , Fluoroquinolonas , Quinolinas , Administração Oral , Adulto , Distribuição por Idade , Idoso , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/sangue , Anti-Infecciosos/urina , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Distribuição por Sexo
15.
J Parasitol ; 87(2): 460-2, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11318589

RESUMO

Adoptively transferred resistance to Schistosoma mansoni in the snail intermediate host Biomphalaria glabrata was measured as a function of miracidial challenge dose. Schistosome-susceptible snails implanted with the amebocyte-producing organ (APO) from resistant donors showed 29 and 39% prevalences of infection after challenge with 5 and 10 miracidia, respectively, but 68-83% prevalences when exposed to 25-200 miracidia. Prevalences in control (untampered) susceptible snails ranged from 97 to 100% at the different miracidial doses. Higher infection prevalences at elevated doses suggest that a range of transferred resistance occurs and possibly that low levels of APO-derived plasma factors or hemocytes in some recipients can be overwhelmed by larger numbers of parasites.


Assuntos
Transferência Adotiva , Biomphalaria/imunologia , Schistosoma mansoni/patogenicidade , Animais , Biomphalaria/parasitologia , Imunidade Inata
16.
J Parasitol ; 87(6): 1360-5, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11780822

RESUMO

A heat-labile plasma factor from genetically resistant 10-R2 Biomphalaria glabrata snails confers passively transferred resistance (PTR) to Schistosoma mansoni when injected into susceptible snails within 24-hr of exposure to miracidia. However, no additional details on PTR have emerged since the initial 1984 report, nor has the plasma resistance factor been characterized. In the present study, new information is provided on the occurrence of resistance factor in plasma of additional types of snails, effect of "priming" resistant plasma donors by prior exposure to miracidia, duration of PTR, molecular weight of resistance factor, and fate of sporocysts in snails with PTR. Susceptible NIH albino snails injected 24 hr prior to exposure to miracidia with individual samples of plasma from a different strain (Salvador B. glabrata) or a different species (B. obstructa) of nonsusceptible snail displayed infection prevalences of 49% or 59% of control levels, respectively, whereas injections of homologous plasma had no effect. PTR was not enhanced by prior exposure of resistant Salvador plasma donors to miracidia. Unexpectedly, PTR induced by injections of Salvador plasma persisted for at least 21 days. The molecular weight of the resistance factor(s) was between 10 and 30 kDa, based on results of centrifugal ultrafiltration. A significantly higher proportion of dead sporocysts occurred in histological sections of tentacles from snails injected with Salvador plasma than in tentacles of snails injected with NIH albino plasma at 7 days postexposure to miracidia. Most dead sporocysts in Salvador plasma-injected snails were undergoing gradual degeneration, rather than rapid, hemocyte-mediated destruction, as occurred in Salvador snails.


Assuntos
Biomphalaria/imunologia , Biomphalaria/parasitologia , Hemolinfa/imunologia , Imunização Passiva , Schistosoma mansoni/imunologia , Animais , Biomphalaria/genética , Imunidade Inata/genética
17.
Dev Comp Immunol ; 24(6-7): 543-51, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10831789

RESUMO

Hearts of the snails Physa virgata and Biomphalaria glabrata were implanted into the hemocoel of B. glabrata. Implants either were microencapsulated in 2.5% agarose or were unencapsulated. Unencapsulated xenografts from P. virgata underwent complete necrosis within 3 days post-implantation (DPI), whereas allografts were still alive at 7 DPI. In the case of microencapsulated implants, both allografts and xenografts were alive at 3 DPI, showing 4.8 and 14.9% pyknosis among myofiber nuclei, respectively. These results suggest that direct cytotoxicity by hemocytes, rather than toxic plasma factors or donor-recipient physiological incompatibility, is responsible for rapid xenograft death. However, both types of microencapsulated grafts were necrotic at 7 DPI. This necrosis may have resulted from oxygen deprivation brought about both by the agarose and by the heterotopic implantation site, inasmuch as microencapsulated allografts and xenografts cultured in saline for 7 days showed only 1.98 and 30% pyknosis, respectively.


Assuntos
Biomphalaria/imunologia , Histocompatibilidade/imunologia , Transplante Heterólogo/imunologia , Animais , Núcleo Celular/patologia , Células Cultivadas , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/patologia , Transplante de Coração/imunologia , Transplante de Coração/mortalidade , Transplante de Coração/patologia , Técnicas Imunológicas , Técnicas In Vitro , Lymnaea , Miocárdio/patologia
18.
J Parasitol ; 86(2): 308-11, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10780550

RESUMO

To measure the longevity of sporocysts of Schistosoma mansoni in nonsusceptible snails (13-16-R1 and Salvador strains of Biomphalaria glabrata, and Biomphalaria obstructa), the head-foot (HF) of miracidia-exposed snails was transplanted into the hemocoel of a susceptible NIH albino recipient at 1-36 days postexposure (DPE). Recipient snails which were not exposed to miracidia then were monitored for infection transferred by the implant, and infection prevalences in recipients of HF transplants from nonsusceptible donors were compared to those in snails implanted with an HF from NIH albino donors. Transplants from NIH albino snails between 1 to 15 DPE infected 98% of recipients. Similarly, at 1 DPE, 69-85% of transplants from nonsusceptible snails contained viable sporocysts, as shown by resulting patent infections in the recipients. Recipient infection prevalence, and presumably numbers of transplants containing viable sporocysts, declined as a function of DPE, and by 5-9 DPE this decrease was significant for all 3 types of nonsusceptible donors. However, viable sporocysts still occurred in B. obstructa and 13-16-R1 B. glabrata as late as 19 and 20 DPE, respectively, and in Salvador B. glabrata as late as 33 DPE. Thus, sporocysts persist in nonsusceptible snails considerably longer than suggested by results of previous histological studies.


Assuntos
Biomphalaria/parasitologia , Schistosoma mansoni/fisiologia , Animais , Biomphalaria/classificação , Interações Hospedeiro-Parasita
19.
Antimicrob Agents Chemother ; 43(11): 2793-7, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10543767

RESUMO

The pharmacokinetics, safety, and tolerability of oral moxifloxacin, a new 8-methoxy quinolone, were assessed in a randomized, double-blind, placebo-controlled study in which healthy male and female volunteers received either 400 mg of moxifloxacin once daily (n = 10) or a placebo once daily (n = 5) for 10 days. Plasma moxifloxacin concentrations on days 1 and 10 were measured by high-performance liquid chromatography and fluorometric detection. Standard pharmacokinetic parameters were estimated by noncompartmental methods. Natural logarithmic estimates for each pharmacokinetic variable of each subject were analyzed by a two-way analysis of variance. Hematology, blood chemistry, vital signs, and adverse events were monitored, and electrocardiograms (ECG) were performed. Plasma moxifloxacin concentrations of predicted therapeutic relevance were achieved in this study. For day 1, the mean maximum concentration of drug in serum (C(max)) and the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) were 3. 4 mg/liter and 30.2 mg. h/liter, respectively. Corresponding means on day 10 were 4.5 mg/liter and 48 mg. h/liter, respectively. On day 10, the mean elimination half-life was approximately 12 h. Plasma moxifloxacin concentrations exceeded the MIC for Streptococcus pneumoniae throughout the 24-h dosing period. The day 1 and day 10 mean AUC/MIC ratios were 121 and 192, respectively, and the mean C(max)/MIC ratios were 13 and 18, respectively. Moxifloxacin was well tolerated; no clinically relevant changes in the standard laboratory tests, vital signs, or ECG were observed. Pharmacokinetic parameters demonstrated linearity, and estimates of pharmacokinetic/pharmacodynamic ratios (AUC/MIC and C(max)/MIC) indicate that the regimen of 400-mg once daily should be effective for treating a variety of infections. Moxifloxacin was found to be safe and well tolerated in healthy volunteers when it was given as a single daily 400-mg dose for 10 days.


Assuntos
Anti-Infecciosos/farmacocinética , Compostos Aza , Fluoroquinolonas , Quinolinas , Adolescente , Adulto , Anti-Infecciosos/efeitos adversos , Área Sob a Curva , Método Duplo-Cego , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Estereoisomerismo
20.
Clin Ther ; 21(3): 513-22, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10321420

RESUMO

Moxifloxacin (BAY 12-8039) is an investigational 8-methoxy-fluoroquinolone with broad-spectrum gram-positive and gram-negative activity. To determine the absolute bioavailability of moxifloxacin, this open-label, randomized, crossover study compared the pharmacokinetic characteristics of a single 100-mg dose administered either orally or intravenously as a 60-minute infusion in 10 healthy male volunteers (mean age [+/- SD], 29.3+/-7.1 years; mean weight [+/- SD], 77.7+/-8.7 kg). Geometric mean values for oral/IV moxifloxacin were as follows: peak serum concentration, 1.15/1.34 mg/L, and area under the concentration-time curve over 48 hours, 9.86/10.89 mg x h/L. The geometric mean absolute bioavailability of oral moxifloxacin was 91.8%. Mean renal clearance was approximately 2.3 L/h after administration of both the single oral and IV formulations, which suggests lack of active tubular secretion of moxifloxacin. Both the oral and IV formulations were well tolerated, with 5 reported possible or probable drug-related adverse events; they included headache, nausea, and localized urticaria. In summary, a single oral dose of moxifloxacin was extensively absorbed in healthy young men. Further studies are necessary in actual patients to confirm the viability of IV to oral conversion at the same dose of moxifloxacin.


Assuntos
Anti-Infecciosos/farmacocinética , Compostos Aza , Fluoroquinolonas , Quinolinas , Administração Oral , Adulto , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Disponibilidade Biológica , Estudos Cross-Over , Relação Dose-Resposta a Droga , Humanos , Infusões Intravenosas , Masculino , Moxifloxacina
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