Phenotypic plasticity in adults of Anticarsia gemmatalis exposed to sub-doses of Bt-based bioinsecticide / Plasticidade fenotípica morfométrica em adultos de Anticarsia gemmatalis Hübner, 1818 expostos a subdoses de Bacillus thuringiensis Berliner, 1911

Anticarsia gemmatalis Hünber, 1818 is one of the main defoliating species in the soybean crop. Bacillus thuringiensis Berliner, 1915, is a bacterium used in the biological control of this pest species. Resistant populations and their sublethal effects caused by the use of the bacteria have already been reported; however, there are no studies on phenotypic plasticity in adulthood exposed to Bt-based bioinsecticide sub-doses. This study aimed to evaluate the morphometry of A. gemmatalis adults under laboratory conditions submitted to the Bt-based bioinsecticide Dipel® over the three generations. The body segments mensuread were width, length, and area of the anterior and posterior wings, the weight of the integument, chest, abdomen, wings, and the whole adult of males and females. Among the treatments, LC5 in the first generation and LC10 in the second generation were those with lower thresholds in relation to the weight of the chest and abdomen, considering the proportions of the body smaller than the females. The female's weight adulthood was reduced by 10% about males, and, only in the first generation. Males have larger body size and more pronounced phenotypic plasticity than females. Here, we demonstrate the first study assessing the phenotypic plasticity of A. gemmatalis adults.

Anticarsia gemmatalis Hünber, 1818 é uma das principais espécies desfolhadoras da cultura da soja. Bacillus thuringiensis Berliner, 1915, é uma bactéria utilizada no controle biológico dessa espécie de praga. Populações resistentes e seus efeitos subletais causados pelo uso da bactéria já foram relatados, no entanto, não há estudos sobre a plasticidade fenotípica na idade adulta exposta a subdoses de bioinseticida à base de Bt. Este trabalho teve como objetivo avaliar a morfometria de adultos de A. gemmatalis em condições de laboratório submetidos ao bioinseticida Dipel® ao longo de três gerações. Os segmentos corporais mensuráveis eram largura, comprimento e área das asas anterior e posterior, o peso do tegumento, tórax, abdômen, asas e todo o adulto de machos e fêmeas. Dentre os tratamentos, CL5 na primeira geração e CL10 na segunda geração foram aqueles com limiares mais baixos em relação ao peso do tórax e abdômen, considerando as proporções do corpo menores que as do sexo feminino. O peso da fêmea na idade adulta foi reduzido em 10% em relação aos machos e, apenas na primeira geração. Os machos têm tamanho corporal maior e plasticidade fenotípica mais pronunciada do que as fêmeas. Este estudo demonstra o primeiro estudo avaliando a plasticidade fenotípica de adultos de A. gemmatalis.

Phenotypic plasticity in adults of Anticarsia gemmatalis exposed to sub-doses of Bt-based bioinsecticide

Abstract Anticarsia gemmatalis Hünber, 1818 is one of the main defoliating species in the soybean crop. Bacillus thuringiensis Berliner, 1915, is a bacterium used in the biological control of this pest species. Resistant populations and their sublethal effects caused by the use of the bacteria have already been reported; however, there are no studies on phenotypic plasticity in adulthood exposed to Bt-based bioinsecticide sub-doses. This study aimed to evaluate the morphometry of A. gemmatalis adults under laboratory conditions submitted to the Bt-based bioinsecticide Dipel® over the three generations. The body segments mensuread were width, length, and area of the anterior and posterior wings, the weight of the integument, chest, abdomen, wings, and the whole adult of males and females. Among the treatments, LC5 in the first generation and LC10 in the second generation were those with lower thresholds in relation to the weight of the chest and abdomen, considering the proportions of the body smaller than the females. The females weight adulthood was reduced by 10% about males, and, only in the first generation. Males have larger body size and more pronounced phenotypic plasticity than females. Here, we demonstrate the first study assessing the phenotypic plasticity of A. gemmatalis adults.

Resumo Anticarsia gemmatalis Hünber, 1818 é uma das principais espécies desfolhadoras da cultura da soja. Bacillus thuringiensis Berliner, 1915, é uma bactéria utilizada no controle biológico dessa espécie de praga. Populações resistentes e seus efeitos subletais causados pelo uso da bactéria já foram relatados, no entanto, não há estudos sobre a plasticidade fenotípica na idade adulta exposta a subdoses de bioinseticida à base de Bt. Este trabalho teve como objetivo avaliar a morfometria de adultos de A. gemmatalis em condições de laboratório submetidos ao bioinseticida Dipel® ao longo de três gerações. Os segmentos corporais mensuráveis eram largura, comprimento e área das asas anterior e posterior, o peso do tegumento, tórax, abdômen, asas e todo o adulto de machos e fêmeas. Dentre os tratamentos, CL5 na primeira geração e CL10 na segunda geração foram aqueles com limiares mais baixos em relação ao peso do tórax e abdômen, considerando as proporções do corpo menores que as do sexo feminino. O peso da fêmea na idade adulta foi reduzido em 10% em relação aos machos e, apenas na primeira geração. Os machos têm tamanho corporal maior e plasticidade fenotípica mais pronunciada do que as fêmeas. Este estudo demonstra o primeiro estudo avaliando a plasticidade fenotípica de adultos de A. gemmatalis.

Phenotypic plasticity in adults of Anticarsia gemmatalis exposed to sub-doses of Bt-based bioinsecticide.

Anticarsia gemmatalis Hünber, 1818 is one of the main defoliating species in the soybean crop. Bacillus thuringiensis Berliner, 1915, is a bacterium used in the biological control of this pest species. Resistant populations and their sublethal effects caused by the use of the bacteria have already been reported; however, there are no studies on phenotypic plasticity in adulthood exposed to Bt-based bioinsecticide sub-doses. This study aimed to evaluate the morphometry of A. gemmatalis adults under laboratory conditions submitted to the Bt-based bioinsecticide Dipel® over the three generations. The body segments mensuread were width, length, and area of the anterior and posterior wings, the weight of the integument, chest, abdomen, wings, and the whole adult of males and females. Among the treatments, LC5 in the first generation and LC10 in the second generation were those with lower thresholds in relation to the weight of the chest and abdomen, considering the proportions of the body smaller than the females. The female's weight adulthood was reduced by 10% about males, and, only in the first generation. Males have larger body size and more pronounced phenotypic plasticity than females. Here, we demonstrate the first study assessing the phenotypic plasticity of A. gemmatalis adults.

Indocyanine green fluorescence angiography versus standard intraoperative methods for prevention of anastomotic leak in colorectal surgery: meta-analysis.

BACKGROUND: Assessment of anastomotic blood perfusion with intraoperative indocyanine green fluorescence angiography (ICG-FA) may be effective in preventing anastomotic leak compared with standard intraoperative methods in colorectal surgery. METHODS: MEDLINE, PubMed, Cochrane Central Register of Controlled Trials and the Cochrane Library were searched for RCTs and observational studies on intraoperative ICG-FA to May 2020. Odds ratios (ORs), risk differences and mean differences (MDs) were calculated with 95 per cent c.i. based on intention-to-treat analysis. The number needed to treat for an additional beneficial outcome was also estimated. RESULTS: Twenty-five comparative studies included a total of 7735 patients. The use of intraoperative ICG fluorescence angiography was linked with a significant reduction in all grades anastomotic leak (OR 0.39 (95 per cent c.i. 0.31 to 0.49), P < 0.001; number needed to treat for an additional beneficial outcome (NNTB) 23) and length of hospital stay (MD -0.72 (95 per cent c.i. -1.22 to -0.21) days, P = 0.006). A significantly lower incidence of grade A (OR 0.33 (0.18 to 0.60), P < 0.001), grade B (OR 0.58 (0.35 to 0.97), P = 0.04) and grade C (OR 0.59 (0.38 to 0.92), P = 0.02) anastomotic leak was demonstrated in favour of ICG-FA. For low or ultra-low rectal resection, the odds of developing anastomotic leakage was 0.32 (0.23 to 0.45) (P < 0.001; NNTB 14). There were no differences in duration of surgery, and no adverse events related to ICG fluorescent injection. CONCLUSION: The use of ICG-FA instead of standard intraoperative methods to assess anastomosis blood perfusion in colorectal surgery leads to a significant reduction in anastomotic leakage and in the need for surgical reintervention for anastomotic leak, especially in patients with low or ultra-low rectal resections.

Development and validation of a staging system for gastric adenocarcinoma after neoadjuvant chemotherapy and gastrectomy with D2 lymphadenectomy.

BACKGROUND: Neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy is commonly used for patients with locally advanced gastric adenocarcinoma. The eighth AJCC ypTNM staging system was validated based on patients undergoing more limited lymphadenectomy (less than D2). The aim of this study was to develop a system for accurate staging of patients with locally advanced gastric adenocarcinoma who receive neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy. METHODS: A modified system of ypTNM was developed, based on overall survival (OS) of patients receiving neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy at Memorial Sloan Kettering Cancer Center, and validated using data from an international cohort of patients who had similar treatment. RESULTS: Of 325 patients in the derivation cohort, 33 (10·2 per cent) had ypT0 N0/+ tumours, which are not classifiable under the AJCC system. The 5-year OS rate for modified ypTNM stages I, II, IIIA and IIIB was 89, 71, 42·3 and 10 per cent respectively, compared with 82, 65·2 and 24·1 for AJCC stages I, II and III respectively. The concordance index (0·730 versus 0·709), estimated area under the curve (0·765 versus 0·740) and time-dependent receiver operating characteristic (ROC) curve throughout the observation period were all superior for modified ypTNM staging. For the validation cohort of 186 patients, the modified system was again better at separating patients into prognostic groups for OS. CONCLUSION: The modified ypTNM staging system improves the accuracy of OS prediction for patients treated with neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy.

A rare case of perforation of the subhepatic appendix by a toothpick in a patient with intestinal malrotation: laparoscopic approach.

Foreign body ingestion is not an uncommon problem in clinical practice. While most ingested foreign bodies pass uneventfully through the gastrointestinal tract, sharp foreign bodies such as toothpicks should cause intestinal perforation. We reported the case of a perforation of the appendix caused by a toothpick, which also pierced the liver without hepatic damages, in a male with an intestinal malrotation and subhepatic appendix. The patient was admitted to our hospital for abdominal pain in the right upper quadrant. An abdominal computed tomography scan revealed the anomalous position of the first portion of the large intestine with inflamed appendix. A laparoscopic appendicectomy and the exploration of the abdominal cavity was performed using minimally invasive technique.

Overexpression of the activated form of the AtAREB1 gene (AtAREB1ΔQT) improves soybean responses to water deficit.

Abscisic acid-responsive element binding protein (AREB1) is a basic domain/leucine zipper transcription factor that binds to the abscisic acid (ABA)-responsive element motif in the promoter region of ABA-inducible genes. Because AREB1 is not sufficient to direct the expression of downstream genes under non-stress conditions, an activated form of AREB1 (AREB1ΔQT) was created. Several reports claim that plants overexpressing AREB1 or AREB1ΔQT show improved drought tolerance. In our studies, soybean plants overexpressing AREB1ΔQT were characterized molecularly, and the phenotype and drought response of three lines were accessed under greenhouse conditions. Under conditions of water deficit, the transformed plants presented a higher survival rate (100%) than those of their isoline, cultivar BR 16 (40%). Moreover, the transformed plants displayed better water use efficiency and had a higher number of leaves than their isoline. Because the transgenic plants had higher stomatal conductance than its isoline under well-watered conditions, it was suggested that the enhanced drought response of AREB1ΔQT soybean plants might not be associated with altered transpiration rates mediated by ABA-dependent stomatal closure. However, it is possible that the smaller leaf area of the transgenic plants reduced their transpiration and water use, causing delayed stress onset. The difference in the degree of wilting and percentage of survival between the 35S-AREB1ΔQT and wildtype plants may also be related to the regulation of genes that protect against dehydration because metabolic impairment of photosynthesis, deduced by an increasing internal CO2 concentration, was not observed in the transgenic plants.

Systematic review and meta-analysis of randomized clinical trials comparing single-incision versus conventional laparoscopic cholecystectomy.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) may offer advantages over conventional laparoscopic cholecystectomy (LC). METHODS: MEDLINE, Embase, PubMed, CINAHL, Cochrane Central Register of Controlled Trials and the Cochrane Library were searched for randomized clinical trials on SILC versus LC until May 2012. Odds ratio (OR) and weight mean difference (WMD) were calculated with 95 per cent confidence intervals (c.i.) based on intention-to-treat analysis. RESULTS: Thirteen randomized clinical trials included a total of 923 procedures. SILC had a higher procedure failure rate than LC (OR 8·16, 95 per cent c.i. 3·42 to 19·45; P < 0·001), required a longer operating time (WMD 16·55, 95 per cent c.i. 9·95 to 23·15 min; P < 0·001) and was associated with greater intraoperative blood loss (WMD 1·58, 95% of c.i. 0·44 to 2·71 ml; P = 0·007). There were no differences between the two approaches in rate of conversion to open surgery, length of hospital stay, postoperative pain, adverse events, wound infections or port-site hernias. Better cosmetic outcomes were demonstrated in favour of SILC as measured by Body Image Scale questionnaire (WMD -0·97, 95% of c.i. -1·51 to -0·43; P < 0·001) and Cosmesis score (WMD -2·46, 95% of c.i. -2·95 to -1·97; P < 0·001), but this was based on comparison with procedures in which multiple and often large ports (10 mm) were used. CONCLUSION: SILC has a higher procedure failure rate with more blood loss and takes longer than LC. No trial was adequately powered to assess safety.

Bacillus thuringiensis Cry1Ia10 and Vip3Aa protein interactions and their toxicity in Spodoptera spp. (Lepidoptera).

The polyphagous pests belonging to the genus Spodoptera are considered to be among the most important causes of damage and are widely distributed throughout the Americas'. Due to the extensive use of genetically modified plants containing Bacillus thuringiensis genes that code for insecticidal proteins, resistant insects may arise. To prevent the development of resistance, pyramided plants, which express multiple insecticidal proteins that act through distinct mode of actions, can be used. This study analyzed the mechanisms of action for the proteins Cry1Ia10 and Vip3Aa on neonatal Spodoptera frugiperda, Spodoptera albula, Spodoptera eridania and Spodoptera cosmioides larvae. The interactions of these toxins with receptors on the intestinal epithelial membrane were also analyzed by binding biotinylated toxins to brush border membrane vesicles (BBMVs) from the intestines of these insects. A putative receptor of approximately 65 kDa was found by ligand blotting in all of these species. In vitro competition assays using biotinylated proteins have indicated that Vip3Aa and Cry1Ia10 do not compete for the same receptor for S. frugiperda, S. albula and S. cosmioides and that Vip3Aa was more efficient than Cry1Ia10 when tested individually, by bioassays. A synergistic effect of the toxins in S. frugiperda, S. albula and S. cosmioides was observed when they were combined. However, in S. eridania, Cry1Ia10 and Vip3Aa might compete for the same receptor and through bioassays Cry1Ia10 was more efficient than Vip3Aa and showed an antagonistic effect when the proteins were combined. These results suggest that using these genes to develop pyramided plants may not prove effective in preventing the development of resistance in S. eridiana.

Genetic characterization of fig tree mutants with molecular markers.

The fig (Ficus carica L.) is a fruit tree of great world importance and, therefore, the genetic improvement becomes an important field of research for better crops, being necessary to gather information on this species, mainly regarding its genetic variability so that appropriate propagation projects and management are made. The improvement programs of fig trees using conventional procedures in order to obtain new cultivars are rare in many countries, such as Brazil, especially due to the little genetic variability and to the difficulties in obtaining plants from gamete fusion once the wasp Blastophaga psenes, responsible for the natural pollinating, is not found in Brazil. In this way, the mutagenic genetic improvement becomes a solution of it. For this reason, in an experiment conducted earlier, fig plants formed by cuttings treated with gamma ray were selected based on their agronomic characteristics of interest. We determined the genetic variability in these fig tree selections, using RAPD and AFLP molecular markers, comparing them to each other and to the Roxo-de-Valinhos, used as the standard. For the reactions of DNA amplification, 140 RAPD primers and 12 primer combinations for AFLP analysis were used. The selections did not differ genetically between themselves and between them and the Roxo-de-Valinhos cultivar. Techniques that can detect polymorphism between treatments, such as DNA sequencing, must be tested. The phenotypic variation of plants may be due to epigenetic variation, necessitating the use of techniques with methylation-sensitive restriction enzymes.

Is inferior mesenteric artery ligation during sigmoid colectomy for diverticular disease associated with increased anastomotic leakage? A meta-analysis of randomized and non-randomized clinical trials.

AIM: A meta-analysis was conducted to compare preservation with ligation of the inferior mesenteric artery (IMA) during sigmoidectomy for diverticular disease. METHOD: Randomized and non-randomized clinical trials were identified using the following electronic databases: Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, BioMed Central, Science Citation Index, Greynet, SIGLE, National Technological Information Service, British Library Integrated Catalogue. The analysed end-points were the anastomotic leakage rate, overall morbidity and 30-day postoperative mortality. RESULTS: Four studies were included involving 400 patients. The anastomotic leakage rate was 7.3% in the preservation group and 11.3% in the ligation group. There was no statistically significant difference between the groups (OR 0.72, 95% CI 0.11-4.76; P=0.73). Overall morbidity and 30-day postoperative mortality were not compared since these data were reported in only one study. CONCLUSION: The meta-analysis did not show any advantage for preservation of the IMA during sigmoid colectomy for diverticular disease in terms of anastomotic leakage.

Quantification of changes in c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells following chemical treatment.

Lung tumors frequently exhibit altered expression of oncogenes and/or tumor suppressor genes. Although some of these alterations are believed to arise from chemical exposure, the ability of specific chemicals to cause distinct changes in gene expression is not well characterized. We previously reported the development of a quantitative reverse transcriptase/polymerase chain reaction (RT/PCR) method for measuring c-myc mRNA levels, and reported that c-myc proto-oncogene expression is significantly increased in small-cell lung carcinoma cells. In the present study, quantitative RT/PCR was used to assess the effect of model toxins cycloheximide (CHX), a protein synthesis inhibitor, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a DNA alkylating agent, on c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells. Expression of c-myc was evaluated at 1-100 microM CHX and MNNG and was compared to the cytotoxic response as measured by the neutral red assay. Cycloheximide elicited a dose-dependent increase in c-myc mRNA levels in NHBE and A549 cells, but did not alter expression of the housekeeping gene beta-actin. A maximum increase for c-myc expression (200% of control) was observed 5 h after treatment with noncytotoxic concentrations. In contrast, MNNG elicited a dose-dependent decrease in c-myc expression in A549 cells, but no significant change in c-myc was observed in NHBE cells. The results from this study suggest that the quantitative RT/PCR method may be an appropriate technique for monitoring gene expression changes following chemical exposure. Hence, these types of studies may assist in the identification of specific chemicals which may induce the genetic alterations involved in the development of lung cancer as well as provide information relevant to the interactive effects of chemicals within complex mixtures.

Efficacy of cefepime in a Staphylococcus aureus endocarditis rat model.

The efficacy of cefepime, a new broad-spectrum cephalosporin, was compared with those of cefpirome, ceftazidime, vancomycin, imipenem-cilastatin and penicillin G in a rat model of endocarditis caused by a methicillin-susceptible strain of Staphylococcus aureus. Rats were infected intravenously with approximately 10(5) cfu of a penicillin-resistant strain of S. aureus 24 h after placement of a catheter into the left ventricle of the heart via the carotid artery. Efficacy was evaluated by comparing bacterial counts in the cardiac vegetations of treated rats with those of untreated controls. Rats treated with cefepime, cefpirome, ceftazidime, imipenem-cilastatin and vancomycin showed a reduction in the number of bacteria recovered from cardiac vegetations compared with infected control animals; penicillin G was ineffective in this respect. Serum concentrations of the study antimicrobials were determined at selected times following the administration of a single subcutaneous dose. The pharmacokinetic parameters of the cephalosporins were similar in these animals. This study shows that cefepime may be of value in the treatment of staphylococcal endocarditis.

Use of amino acid N-carboxy anhydride in the synthesis of peptide prodrug derivatives (including beta-chloroalanyl) of C4-beta-aminoalkyl carbapenems. In vitro and in vivo activities.

Mono- and dipeptide derivatives of C4-beta-aminoalkyl carbapenems were synthesized by the use of amino acid N-carboxy anhydride for the peptide bond formation. They were shown to act as prodrugs in vivo while imparting the much desired chemical stability. The beta-chloroalanyl derivative was suggested to act, in part, as a "dual-purpose" antibacterial.

Fluoronaphthyridines and -quinolones as antibacterial agents. 5. Synthesis and antimicrobial activity of chiral 1-tert-butyl-6-fluoro-7-substituted-naphthyridones.

A series of novel 7-substituted-1-tert-butyl-6-fluoronaphthyridone-3- carboxylic acids has been prepared. These derivatives are characterized by chiral aminopyrrolidine substituents at the 7 position. In this paper we report the full details of the asymmetric synthesis of this series of compounds. Structure-activity relationship studies indicate that the absolute stereochemistry at the asymmetric centers of the pyrrolidine ring is critical for maintaining good activity. Compounds 60 and 61 (3-amino-4-methylpyrrolidine enantiomers) were selected for preclinical evaluation.

Comparison of in vitro biological properties and mouse toxicities of three thymidine analogs active against human immunodeficiency virus.

Three analogs of thymidine, D4T [2',3'-didehydro-2',3'-dideoxythymidine; 1-(2,3-dideoxy-beta-D-glyceropent-2-enofuranosyl)thymine], FddT (3'-fluoro-3'-deoxythymidine), and AZT (3'-azido-3'-deoxythymidine), were compared in biological tests designed to assess their potential utility as anti-human immunodeficiency virus (HIV) agents. The in vitro potencies of these compounds against HIV infection in CEM cells were measured, with FddT and AZT being more potent than D4T. The cytotoxicities of D4T, FddT, and AZT for CEM cells were comparable. The triphosphates of these three derivatives inhibited purified HIV reverse transcriptase, and their affinities for this polymerase were found to be 1 or 2 orders of magnitude greater than that for the normal substrate, dTTP. D4T was less toxic than FddT or AZT for cultured human and mouse bone marrow cells (granulocyte-macrophage CFU). The three compounds had similar toxicities for human progenitor erythrocyte burst-forming units. In a 30-day mouse toxicity study, AZT and FddT produced a similar spectrum of hematopoietic toxicities. These toxic effects occurred at much lower doses of FddT than of AZT. At the higher doses of FddT, a significant incidence of lethality occurred. By contrast, D4T was considerably less toxic than both AZT and FddT in this study. The dose-limiting toxicity of D4T in mice was hepatotoxicity. The very different phosphorylation patterns of D4T, its lower toxicity, and its comparable potency relative to FddT and AZT suggest that the potential of D4T as an anti-HIV agent should be further explored.

In vitro and in vivo antibacterial activities of BMY 40062, a new fluoronaphthyridone.

The in vitro and in vivo activities of a new naphthyridone, BMY 40062, were compared with those of ciprofloxacin and ofloxacin. BMY 40062 showed about threefold more activity than ciprofloxacin showed and four- to eightfold more activity than ofloxacin showed against staphylococci, streptococci, and enterococci. BMY 40062 showed generally twofold less activity than ciprofloxacin showed against most species of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. but twofold more activity than ofloxacin showed against these organisms. BMY 40062 and ofloxacin were more active than ciprofloxacin against Bacteroides fragilis and Clostridium difficile. The antiureaplasmal and antichlamydial activities of BMY 40062 were similar to those of the tetracyclines and were 4- and 16-fold, respectively, higher than those of ciprofloxacin. The in vitro activities of BMY 40062 were influenced by pH and magnesium, although these factors appeared to affect the activity of BMY 40062 against P. aeruginosa to a lesser extent than those of ciprofloxacin and ofloxacin. BMY 40062 was found to be bactericidal, and cross-resistance with other fluoroquinolones was observed. In mouse protection tests, the efficacy of BMY 40062 reflected its in vitro potency. BMY 40062 exhibited longer half-life, higher maximum concentration in serum, greater area under the curve, and better bioavailability in mice after oral dosing than ciprofloxacin. Compared with ofloxacin, BMY 40062 had a lower maximum concentration in serum but a much longer half-life in mice. BMY 40062 was more effective than ciprofloxacin and ofloxacin in penetrating mouse macrophages and killing macrophage-associated Staphylococcus aureus.

Protection of mice against Listeria monocytogenes infection by recombinant human tumor necrosis factor alpha.

Recombinant human tumor necrosis factor alpha (rHuTNF-alpha) administered intravenously to mice resulted in enhanced resistance to a lethal challenge infection of Listeria monocytogenes given 24 h later. The observed protection was lost following treatment of the rHuTNF-alpha preparations with rabbit polyclonal antibody rHuTNF-alpha but not with normal rabbit immunoglobulin G.