Local and systemic effects of cat allergen nasal provocation.

BACKGROUND: Cat allergen is widely distributed in homes and schools; allergic sensitization is common. OBJECTIVE: To develop a model of cat allergen nasal challenge to establish dose-response and time-course characteristics and investigate local and systemic biomarkers of allergic inflammation. METHODS: Nineteen cat-allergic individuals underwent titrated nasal challenge, range 0.243 to 14.6 µg/mL Fel d1, and matched diluent-only provocation. Clinical response to 8 h was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Nasal fluid was collected using polyurethane sponges and analysed by ImmunoCAP and multiplex assays. Whole blood flow cytometry for basophil surface CD63, CD107a, and CD203c was carried out at baseline and 6 h post-challenge. RESULTS: A dose-response to allergen was seen in symptom scores and PNIF, maximal at 10 000 BU/mL (4.87 µg/mL Fel d1), P < 0.0001 vs. diluent. Nasal fluid tryptase was elevated at 5 min after challenge (P < 0.05 vs. diluent); eotaxin, IL-4, -5, -9, and -13 were increased at 8 h (P < 0.05 to P < 0.0001 vs. diluent); TSLP was undetectable; IL-10, IL-17A, and IL-33 were unchanged compared to diluent challenge. Nasal fluid IL-5 and IL-13 correlated inversely with PNIF after challenge (IL-5, r = -0.79, P < 0.0001; IL-13, r = -0.60, P = 0.006). Surface expression of CD63 and CD107a was greater at 6 h than at baseline, both in the presence (both P < 0.05) and absence (CD63, P < 0.01; CD107a, P < 0.05) of in vitro allergen stimulation; no changes were seen on diluent challenge day. CONCLUSIONS: Cat allergen nasal challenge produces local and systemic Th2-driven inflammatory responses and has potential as a surrogate outcome measure in clinical trials.

Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge.

RATIONALE: Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments. OBJECTIVE: To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study. METHODS: We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n = 14) compared with immunotherapy-treated allergics (n = 14), plus a nonatopic control group (n = 14). Volunteers underwent a standardized NAC with 2000 biological units of timothy grass allergen (equivalent to 1.3 µg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed. RESULTS: Immunotherapy-treated patients had lower symptom scores (P = 0.04) and higher PNIF (P = 0.02) after challenge than untreated allergics. They had reduced early (P = 0.0007) and late (P < 0.0001) skin responses, and lower retrospective seasonal symptom scores (P < 0.0001). Compared to untreated allergics, immunotherapy-treated patients had reduced nasal fluid concentrations of IL-4, IL-9 and eotaxin (all P < 0.05, 8 h level and/or area under the curve comparison), and trends for reduced IL-13 (P = 0.07, area under the curve) and early-phase tryptase levels (P = 0.06). CONCLUSIONS: Nasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies.

Ostracods as pollution indicators in Lap An Lagoon, central Vietnam.

Southeast Asia is particularly susceptible to the negative impacts of increasing coastal pollution as coastal populations and cities grow at unprecedented rates. Although water chemistry can be monitored, there are greater advantages in using bioindicators as reflectors of the combined effect of multiple pollution types on coastal ecosystem health and for early detection of the negative impacts of pollutants on biotic systems. This study explores the utility and application of ostracods as pollution bioindicators and examines the response of ostracod assemblages to variable pollution in Lap An Lagoon, central Vietnam. From 14 sites within the lagoon, 79 species of 46 genera were identified and sediment grain size, total organic carbon, organic matter and heavy metal concentration were measured. Cluster analysis, detrended correspondence analysis and canonical correspondence analysis identified four distinct ostracod biofacies that were highly correlated to the physical environmental variables (salinity, depth, sediment type, heavy metal concentrations, total organic carbon and organic matter) and are shown to be the main factors controlling ostracod biofacies. Low ostracod diversities were found in silty sediments with heavy metal concentrations likely toxic. Sinocytheridea impressa was indicative of a marginally polluted environment within the lagoon. This study provides evidence for the potential for Southeast Asian ostracods to be used in water quality assessments and the data collected can be used as a baseline for future pollution monitoring.

Effect of intermittent infusions of glucose-containing crystalloid cardioplegic solution on myocardial tissue lactic acid and recovery of contractility.

The objective of this study was to determine the effects of single or intermittent infusions of cardioplegic solution with glucose (5 gm/L) or without glucose on myocardial tissue lactic acid and recovery of myocardial contractility following 80 minutes of total ischemia at 28 degrees C in the isolated, blood-perfused, beating rabbit heart. Ischemia without cardioplegia increased tissue lactic acid (6.79 mg/gm tissue) above the control value (0.9 mg/gm tissue), p less than 0.0025). Lactic acid following single infusions with (4.19 mg/gm tissue) or without glucose (3.67 mg/gm tissue) was significantly greater (p less than 0.0025) than tissue lactic acid following intermittent infusions with (1.06 mg/gm tissue) or without glucose (1.05 mg/gm tissue). Cardioplegic arrest in all cases significantly decreased tissue lactate accumulation when compared to arrest without cardioplegia (p less than 0.01). The decrease in myocardial contractility demonstrated when no cardioplegic protection was employed (86% recovery) was completely eliminated (100% recovery) with a single-bolus infusion of cardioplegic solution containing glucose (p less 0.025). Intermittent infusions of cardioplegic solution containing glucose (92% recovery) and single infusions without glucose (93% recovery) also improved recovery of contractility following ischemia, but the results were not statistically significant.

Comparative genotoxicity of quinolone and quinolonyl-lactam antibacterials in the in vitro micronucleus assay in Chinese hamster ovary cells.

The in vitro micronucleus assay is gaining increased attention as a potential alternative to the standard in vitro metaphase analysis assay. In particular, the in vitro micronucleus assay has been proposed as a useful method for chemicals that induce both structural and numerical chromosome alterations, such as DNA gyrase/topoisomerase inhibitors. In this study, we compared the micronucleus-inducing activity of quinolonyl-lactam antibacterials that inhibit DNA-gyrase and bind to penicillin-binding proteins relative to the activity of structurally related quinolone antibacterials that also inhibit DNA-gyrase. All of the quinolones that were structurally related to the quinolonyl-lactams were cytotoxic and induced large increases in the frequency of micronucleated binucleated cells (MNBC) at concentrations between 0.02 and 0.16 mM. These changes were larger than those seen with the commercial quinolones, ciprofloxacin (cytotoxic at > or = 0.57 mM and MNBC at > or = 0.3 mM) and nalidixic acid (cytotoxic at 1.8 mM and no MNBC up to this dose). In contrast, the quinolonyl-lactams were not cytotoxic up to 1.0 mM concentrations and induced either no MNBC or a low frequency of MNBC at higher concentrations compared to the quinolones. Quinolonyl-lactams appear to be less cytotoxic and genotoxic than structurally related quinolones. These results add to the growing database on the in vitro micronucleus assay in general, and more specifically to the relatively small database for the in vitro micronucleus assay in Chinese hamster ovary cells.

Two preliminary studies on sleep and psychotherapy.

Two preliminary studies were conducted to assess the effects of an intensive outpatient psychotherapy, Feeling Therapy, on sleep. This therapy was chosen because of its demonstrated ability to affect its patients' dreams. In the first study a newly entering female patient was recorded across the first three weeks of intensive daily therapy. In contrast to two control subjects recorded across a similar time period, she demonstrated low REM times and short REM latencies on the average, and considerably greater variability in nearly every parameter. In the second study, two patients were recorded across three days (the middle of which was the day of a therapy session) first when new in therapy and then again after two and one-half years of therapy. It was found that when new in therapy both subjects spent nights of significantly altered sleep the day of the therapy session. One subject showed no REM sleep whatsoever while the other showed a 10 min REM latency and low REM time. The significance of these findings and the direction of future research is discussed.

Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems.

This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems. Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones. Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase. Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump.

Delayed recovery following hypothermic arrest in rabbit myocardium.

The purpose of this investigation was to determine the relationship between the duration of myocardial ischemia at 15 degrees C and the time required for the myocardium to recover maximum contractile function following the ischemia. The isolated blood perfused rabbit heart was used as a model of myocardial ischemia. Hearts from 22 New Zealand white rabbits were divided into four groups. In Group I seven hearts were subjected to 15 minutes of ischemia at 15 degrees C. In Group II five hearts were subjected to 30 minutes of ischemia at 15 degrees C. In Group III and IV the ischemia time was extended to 60 and 120 minutes, respectively. Following the ischemia each heart was reperfused at normothermia and papillary muscle contractility was measured and used as an index of myocardial recovery. Hearts in Group I recovered their maximum contractile function after an average of 22.5 minutes. Those in Groups II, III, and IV were fully recovered after 31.7, 38.2, and 45.5 minutes, respectively. The study indicates that the time required for the maximum recovery of myocardial contractility following myocardial ischemia increases at a decreasing rate with an increase in the duration of the ischemia at 15 degrees C.

Effects of psychot herapy on REM latency and REM time.

This study investigated the effect of a functional psychotherapy on the sleep EEG patterns of 6 patients. Contrary to original expectations no significant group differences in REM time and REM latency were found between two nights following therapy sessions and two normal nights. However, across the 4 nights the patients exhibited an average REM latency of 71 min. which was significantly shorter than that recorded in an independent study with the same design and a similar subject population. Clausen, Sersen, and Lidsky (1974) reported an average REM latency of 107.3 min. for 10 normal subjects also recorded across four nights. This result is compared with those in several other studies and discussed in relation to possible changes in dream patterns.

Psychophysiological correlates of the spontaneous K-complex.

A pilot study covering three nights and two studies were carried out to investigate the psychophysiological correlates of the spontaneous K-complex in relation to intense psychotherapy. The pilot study produced evidence that the K-complex was not consistent and stable within or across nights and that its variability might be sensitive to psycho-emotional influences. In the first major study 2 subjects were recorded non-consecutively over a 3-wk. period during experience of intensive therapy while in the second 6 subjects were studied before and after two therapeutic sessions. Results indicated that nights after therapy differed significantly from baseline nights and a significant interaction took place between subjects and therapy on one or more variables of the K-complex and several eye movement indices. Some relationship to length of time in therapy was also noted. These findings were interpreted to indicate a possible relationship between complete expression of feeling and the occurrence of phasic events in the sleeping EEG.

A reapplication of the process scoring system for dreams.

The first application of the new Process Scoring System for dreams was made in an intensive longitudinal case study of 1 S over a 5 1/2 year period. In this second application, the dreams of a sample of 5 experienced Feeling Therapy patients were compared to those of 5 control Ss. As in the first study, considerable support was found for both the transformation hypothesis, which holds that it is possible to shift from a symbolic mode of dream behavior to a directly expressive one, and the parallelism hypothesis, which holds that the expression of affect in dreams parallels the expression of affect in waking and vice versa.

Application of the Process Scoring System to waking, dream and therapy reports.

Extended the Process Scoring System, originally developed for measuring dream dynamics and content, to waking and therapy experiences and applied it in a study of 5 new and 5 experienced Ss in an intensive outpatient psychotherapy. Two areas were examined: First, differences on process and content variables related to length of time in therapy and, second, the parallel relationship in these variables between waking, dream, and therapy experiences. The Process Scoring System proved useful in measuring these variables in all three types of experiences. The results indicated significant differences between the new and experienced patients and measurable interaction between the waking, dream, and therapy areas.

The identification and characterization of hydrazinyl urea-based antibacterial agents through combinatorial chemistry.

An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.