Cage Exposure Research Articles

Host Status of Persian Lime (Citrus latifolia Tan.) to Oriental Fruit Fly and Mediterranean Fruit Fly (Diptera: Tephritidae) in Hawai'i.

We investigated the host status of harvest-ready green Persian lime, Citrus x latifolia Tan. (Rutaceae), to Oriental fruit fly (Bactrocera dorsalis [Hendel]) and Mediterranean fruit fly (Ceratitis capitata [Wiedemann]) (Diptera: Tephritidae) using laboratory and field studies. In forced-infestation small cage exposures (using 25 × 25 × 25 cm screened cages with 50 gravid females) and large olfactometer cage tests (using 2.9 × 2.9 × 2.5 m walk-in screened cages with 100 gravid females), punctured limes were infested by Oriental fruit fly and Mediterranean fruit fly at low rates compared to papaya controls, whereas undamaged intact fruit was not infested. Field collection and packing of 45,958 commercial export-grade fruit and subsequent incubation to look for natural infestation resulted in no emergence of fruit flies. Forced infestation studies in the field using sleeve cages to enclose fruit with a high density of fruit flies (50 gravid females) on the tree also showed no infestation. Commercial export-grade Persian lime fruit should be considered a conditional nonhost for Oriental fruit fly and Mediterranean fruit fly.

PERUBAHAN JUMLAH SEL PURKINJE SEREBELUM TIKUS WISTAR JANTAN SETELAH PEMAPARAN ROKOK ELEKTRIK

Design, taste, marketing and perceptions of safety from e-cigarettes have increased the appeal of e-cigarettes to young people around the world so that their use continues to increase. This is one of the threats in efforts to reduce the prevalence of smokers aged 10-18 years in Indonesia. Electric cigarettes cause oxidative stress while the brain is vulnerable to oxidative stress because it requires large amounts of oxygen. This experimental study with a posttest only control design aimed to determine changes in histological structure and number of male Wistar rat cerebellum Purkinje cells after exposure to electric cigarettes. This study used a sample of 32 male wistar rats (Rattus norvegicus) which were divided into 4 treatment groups: group A (without treatment), group B (put in an exposure cage), group C (given exposure to electric cigarettes 15 times in a cage exposure), and group D (given exposure to e-cigarettes 30 times in the exposure cage). Exposure to e-cigarettes was given for 50 days, then sacrificed and samples were made with Hematoxylin Eosyn (HE) staining. The results showed that the number of cerebellar purkinje cells in male Wistar rats exposed to electric cigarettes decreased significantly and there was a significant difference in the number of cells between 15 and 30 exposures and karyolysis occurred in the cells. E-cigarettes cause core damage and decrease in the number of Purkinje cells in the cerebellum of male wistar rats.

Environmental Assessment with Cage Exposure in the Neva Estuary, Baltic Sea: Metal Bioaccumulation and Physiologic Activity of Bivalve Molluscs

The rise in anthropogenic impacts on the marine environment requires new water management. The use of a triadic approach (bioaccumulation, bioassay, and physiological biomarkers) has been shown to have good applicability for the comparative assessment of the environmental state of the Neva Estuary (Gulf of Finland, Baltic Sea). The novelty of the methodological approach of the study was that it involved both active and passive bio-monitoring methods for assessing the quality of estuarine environment. The classical analyses of metal concentration in bottom sediments, in field biota (fish and molluscs), and in caged molluscs were accompanied by a bioassay of sediment toxicity using amphipods. The physiological state of molluscs kept in cages was assessed according to two functional characteristics, such as cardio-tolerance and metabolic activity (oxygen consumption rate), after exposition in cages. The method of active monitoring (caging exposure with molluscs) as a measurement of parameters in clean molluscs has proven itself well in controlling the accumulation of both metals and oil products. Macroalgae that are abundant in estuarine ecosystems are also good indicators of metals, at least showing the transition from bottom sediments to the next level of food webs. Unionid molluscs were found to be a more sensitive and effective indicator of contaminant accumulation than dreissenid molluscs, characterized by a low tolerance to changeable environmental conditions in the estuarine ecosystem and rather high mortality in cages. Our results have shown that caging exposure with unionids can be a widely used methodological approach for the assessment of estuarine environmental quality through the determination of metal concentrations in molluscs and their physiological state.

Poor Host Status of Australian Finger Lime, Citrus australasica, to Ceratitis capitata, Zeugodacus cucurbitae, and Bactrocera dorsalis (Diptera: Tephritidae) in Hawai'i.

Simple SummaryTephritid fruit flies are major economic pests for fruit production and impede international trade. Different host fruits are known to vary in their suitability for fruit flies to complete their life cycle. International regulatory standards that define the legal host status for tephritid fruit flies categorize fruits as a natural host, a conditional host, or a nonhost. For those fruits that are natural or conditional hosts, infestation rate can vary as a spectrum ranging from highly attractive fruits supporting large numbers of fruit flies to very poor hosts supporting low numbers. Finger lime, Citrus australasica, is a new crop in Hawai’i, and no information existed on its susceptibility to Hawai’i’s tephritid fruit fly pests. Host status testing was conducted using no-choice cage tests and field collections. Ceratitis capitata and Zeugodacus cucurbitae readily oviposited into finger limes, but individuals rarely developed to the pupal or adult stage. Finger lime was not infested by Bactrocera dorsalis and is probably a nonhost. For export, a postharvest treatment may still be required despite the very low infestation rate. Heat treatment, irradiation, and a systems approach are options to reduce the risk of exporting tephritid fruit flies in Hawai’i finger limes.We examined the host status of the Australian finger lime, Citrus australiasica F. Muell. (Rutaceae), to Hawai’i’s tephritid fruit fly pests using laboratory and field studies. In high-density (500 flies, 1:1 males and females) no-choice cage exposures (25 × 25 × 25-cm cage size), both undamaged and punctured finger limes were infested by Ceratitis capitata and Zeugodacus cucurbitae at a low rate compared to papaya controls, whereas Bactrocera dorsalis did not infest undamaged fruit, suggesting finger lime is a nonhost. In low-density (50 females) no-choice cage exposures, C. capitata and Z. cucurbitae readily oviposited in undamaged fruit but individuals rarely developed to the pupal or adult stage. For C. capitata, 274 finger limes exposed to 2000 gravid females, which laid an estimated 14,384 eggs, produced two pupae and no adults. For Z. cucurbitae, 299 fruit exposed to 2000 gravid females, which laid an estimated 4484 eggs, produced four pupae and one adult. Field sampling of undamaged fruit from the tree and off the ground from commercial farms produced five C. capitata pupa and one adult from 1119 fruit, for an infestation rate of 0.05 flies per kilogram of fruit; field collections found no natural Z. cucurbitae or B. dorsalis infestation, but the number of fruit available was too low to demonstrate nonhost status with a high degree of confidence.

Multicomponent drug Neurexan mitigates acute stress-induced insomnia in rats.

The aim of this study was to determine whether the multicomponent drug Neurexan could mitigate acute insomnia after exposure to a psychosocial stressor. We administered Neurexan orally to rats and examined stress-induced insomnia using the male rat dirty cage exchange method. The neurocircuitry and electrophysiological correlates of the model are characterised, and it represents various human insomnia conditions. Male rats were randomly assigned in a crossover design to six treatment groups and electroencephalography (EEG) electrodes attached. Three groups were exposed to a cage inhabited by another male rat for a week and the other three groups received a clean cage. Prior to cage change, rats were given either no drug, vehicle control or Neurexan. Non-rapid eye movement (NREM) sleep, REM sleep, and waking were assessed manually via EEG recordings. Group means were compared for sleep latency and for the 2h after cage change for: time in each state, state-specific episode duration/frequency, in addition to NREM delta, gamma and REM theta EEG spectral power. Rats administered Neurexan fell asleep faster than vehicle-treated rats and spent less time awake with shorter, albeit more waking episodes and increased NREM episodes after dirty cage exposure. Neurexan-treated rats given dirty cages were not statistically different on any outcomes from Neurexan-treated rats given clean cages, thereby mitigating the stressor. In the EEG power spectra analysed, changes between treatment groups were not detected. This research confirms that Neurexan treatment has somnogenic effects and ameliorates psychological stressor-induced acute insomnia.

Rationale for Small Glenoid Baseplate: Position of Central Cage within Glenoid Vault (Exactech® Equinoxe® Reverse System)

BackgroundGlenoid baseplate location is important to good clinical outcomes of reverse total shoulder arthroplasty (RTSA). The glenoid vault is the determining factor for glenoid baseplate location, but, to date, there are no reports on the effect of central cage location within the glenoid vault on RTSA outcomes when using the Exactech® Equinoxe® Reverse System. The purpose of this study was to determine the appropriate cage location in relation to the glenoid vault and monitor for vault and/or cortex penetration by the cage.MethodsData were retrospectively collected from the Samsung Medical Center (SMC) and Seoul National University Bundang Hospital (SNUBH). Patients who underwent RTSA between November 2016 and February 2018 were enrolled. Glenoid vault depth, central cage location within the vault were examined. Inferior glenoid rim–center distance, inferior glenoid rim–cage distance, and center–cage center distances were collected.ResultsTwenty-two patients were enrolled. Three SNUBH patients had inappropriate central cage fixation (33.3%) versus 4 SMC patients (30.8%). All cage exposures were superior and posterior to the glenoid vault. Mean center–cage distance was 5.0 mm in the SNUBH group and 5.21 mm in the SMC group. Center–prosthesis distance was significantly longer in the inappropriate fixation group than in the appropriate fixation group (p<0.024).ConclusionsTo ensure appropriate glenoid baseplate fixation within the glenoid vault, especially in a small glenoid, the surgeon should place the cage lower than usually targeted, and it should overhang the inferior glenoid rim.

Rapid Loss of Resistance to Satyrization in Invasive Mosquitoes and the Effects of Age on Interspecific Mating Frequency.

In several areas where Aedes aegypti (L.) (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) have come in contact following successful invasions, Ae. aegypti have been rapidly displaced by Ae. albopictus. Recent work has confirmed that mating interference, in the form of satyrization, is likely a driving factor in these competitive displacements. However, in sites of sympatry, Ae. aegypti females evolve resistance to satyrization, and in the laboratory, satyrization-susceptible Ae. aegypti can evolve resistance within a few generations of cage exposure to Ae. albopictus. The resistance trait may be costly to maintain, as satyrization-resistant females have been shown to invest more time in mate selection. Here, we show that increased satyrization-resistance does not persist in the absence of satyrization pressure, confirming a cost to maintaining this trait. Ae. aegypti lines that had been previously selected for increased satyrization-resistance demonstrated rapid decreases in this trait over eight generations. Support for the hypothesis that condition-dependent mate preferences lead to variation in mating choice among individuals of differing quality within a population has been accumulating. Here we examine how age-related changes in reproductive effort or reproductive value may result in age-dependent mate choice. We hypothesize that older, lower quality individuals may be more likely to accept a subpar mating, in this case an interspecific mating. Our results demonstrate that mosquito age significantly affects interspecific mating rates with older mosquitoes (male and female) engaging in interspecific mating more frequently than younger counterparts (26.32 vs 9.41%). We discuss the possibility of age-related signal variation causing the breakdown of mating barriers with age.

Developmental manganese, lead, and barren cage exposure have adverse long-term neurocognitive, behavioral and monoamine effects in Sprague-Dawley rats

Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES households experience more stress and are more likely to be exposed to environmental neurotoxins such as lead (Pb) and manganese (Mn) than children in higher SES households. Co-exposure to stress, Pb, and Mn during early development may increase the risk of central nervous system dysfunction compared with unexposed children. To investigate the potential interaction of these factors, Sprague-Dawley rats were bred, and litters born in-house were culled on postnatal day (P)1 to 6 males and 6 females. One male and female within each litter were assigned to one of the following groups: 0 (vehicle), 10 mg/kg Pb, 100 mg/kg Mn, or 10 mg/kg Pb + 100 mg/kg Mn (PbMn), water gavage, and handled only from P4–28 with half the litters reared in cages with standard bedding (29 litters) and half with no bedding (Barren; 27 litters). Mn and PbMn groups had decreased anxiety, reduced acoustic startle, initial open-field hypoactivity, increased activity following (+)-methamphetamine, deficits in egocentric learning in the Cincinnati water maze (CWM), and deficits in latent inhibition conditioning. Pb increased anxiety and reduced open-field activity. Barren-reared rats had decreased anxiety, CWM deficits, increased startle, and initial open-field hyperactivity. Mn, PbMn, Pb Barren-reared groups had impaired Morris water maze performance. Pb altered neostriatal serotonin and norepinephrine, Mn increased hippocampal serotonin in males, Mn + Barren-rearing increased neostriatal serotonin, and Barren-rearing decreased neostriatal dopamine in males. At the doses used here, most effects were in the Mn and PbMn groups. Few interactions between Mn, Pb, and rearing stress were found, indicating that the interaction of these three variables is not as impactful as hypothesized.

Role of glucocorticoid receptor-mediated mechanisms in cocaine memory enhancement

The basolateral amygdala (BLA) is a critical site for the reconsolidation of labile contextual cocaine memories following retrieval-induced reactivation/destabilization. Here, we examined whether glucocorticoid receptors (GR), which are abundant in the BLA, mediate this phenomenon. Rats were trained to lever press for cocaine reinforcement in a distinct environmental context, followed by extinction training in a different context. Rats were then briefly exposed to the cocaine-paired context (to elicit memory reactivation and reconsolidation) or their home cages (no reactivation control). Exposure to the cocaine-paired context elicited greater serum corticosterone concentrations than home cage stay. Interestingly, the GR antagonist, mifepristone (3–10 ng/hemisphere), administered into the BLA after memory reactivation produced a further, dose-dependent increase in serum corticosterone concentrations during the putative time of cocaine-memory reconsolidation but produced an inverted U-shaped dose-effect curve on subsequent cocaine-seeking behavior 72 h later. This effect was anatomically selective, dependent on memory reactivation (i.e., not observed after home cage exposure), and did not reflect protracted hyperactivity. However, the effect was also observed when mifepristone was administered after novelty stress that mimics drug context-induced hypothalamic-pituitary-adrenal (HPA) axis activation without explicit memory reactivation. Together, these findings suggest that, similar to explicit memory retrieval, a stressful event is sufficient to destabilize cocaine memories and permit their manipulation. Furthermore, BLA GR stimulation exerts inhibitory feedback upon HPA axis activation and thus suppresses cocaine-memory reconsolidation.

Non-host status of papaya cultivars to the oriental fruit fly, Bactrocera dorsalis (Diptera: Tephritidae), in relation to the degree of fruit ripeness

AbstractPhytosanitary measures are a major barrier to trade in papaya. We assessed the infestation of tephritid fruit flies on different stages of maturity of papaya, to determine its non-host stage of maturity, for market access. Papaya fruits were collected from Kilifi and Embu counties, Kenya from March 2013 to December 2014, to assess the level of infestation by fruit flies according to the degree of fruit ripening. In all locations, no fruit fly infestation was recorded on papaya when fruits were at the 0, 25 and 50% yellow fruit ripening stage.Bactrocera dorsalis(Hendel) was, however, observed attacking fruits when papaya fruits were at 75 and 100% all yellow (fully ripe fruit ripening stage) with infestations of 0.19−0.51B. dorsalis/kg fruit and 0.24−1.24B. dorsalis/kg fruit, respectively, in all locations. Field cage exposure ofB. dorsalisto fruits of five papaya cultivars—‘Papino’, ‘Neo Essence’, ‘Sunrise Solo’, ‘Tainung No. 1’ and ‘Tainung No. 2’ in Manica Province, Mozambique—showed thatB. dorsalisdid not infest fruits at 0, 25 and 50% yellow ripening stages at the densities of 50 and 100 flies per cage. However, at 75% yellow ripening stage, up to 13.1 pupae/kg of fruits was recorded at a density of 150 flies per cage in Tainung No. 1, and infestation ranged from 4.5 to 136 pupae/kg fruits at 100% yellow ripening stage across all the cultivars and infestation densities. Laboratory evaluation of volatiles emanating from freshly crushed papaya pulp of four cultivars: ‘Sunrise Solo’, ‘Red Lady’, ‘Papayi’ and ‘Apoyo’ on egg viability ofB. dorsalisshowed that at 0, 25 and 50% yellow, egg hatchability was inhibited, suggesting that semiochemical compounds present in green tissues of papaya prevent egg development, although this effect was variable across the four cultivars and ripening stages. Export papaya is harvested at less than 40% yellow ripening stage. Our results, therefore, suggest that quarantine treatment for fruits at this ripening stage is inconsequential, asB. dorsalisdoes not infest papaya fruits at this stage; thus, authorities should permit entry of these papaya cultivars of less than 40% yellow ripening stage to quarantine-sensitive markets.

Stress impairs the efficacy of immune stimulation by CpG-C: Potential neuroendocrine mediating mechanisms and significance to tumor metastasis and the perioperative period

We recently reported that immune stimulation can be compromised if animals are simultaneously subjected to stressful conditions. To test the generalizability of these findings, and to elucidate neuroendocrine mediating mechanisms, we herein employed CpG-C, a novel TLR-9 immune-stimulating agent. Animals were subjected to ongoing stress (20-h of wet cage exposure) during CpG-C treatment, and antagonists to glucocorticoids, β-adrenoceptor, COX2, or opioids were employed (RU486, nadolol, etodolac, naltrexone). In F344 rats, marginating-pulmonary NK cell numbers and cytotoxicity were studied, and the NK-sensitive MADB106 experimental metastasis model was used. In Balb/C mice, experimental hepatic metastases of the CT-26 colon tumor were studied; and in C57BL/6J mice, survival rates following excision of B16 melanoma was assessed – both mouse tumor models involved surgical stress. The findings indicated that simultaneous blockade of glucocorticoid and β-adrenergic receptors improved CpG-C efficacy against MADB106 metastasis. In mice bearing B16 melanoma, long-term survival rate was improved by CpG-C only when employed simultaneously with blockers of glucocorticoids, catecholamines, and prostaglandins. Prolonged stress impaired CpG-C efficacy in potentiating NK activity, and in resisting MADB106 metastasis in both sexes, as also supported by in vitro studies. This latter effect was not blocked by any of the antagonists or by adrenalectomy. In the CT26 model, prolonged stress only partially reduced the efficacy of CpG-C. Overall, our findings indicate that ongoing behavioral stress and surgery can jeopardize immune-stimulatory interventions and abolish their beneficial metastasis-reducing impacts. These findings have implications for the clinical setting, which often involve psychological and physiological stress responses during immune-stimulation.

Post-Release Performance and Assessment of Cage-Conditioned Japanese Flounder, Paralichthys olivaceus, in Wakasa Bay, Japan

Conditioning is the process of providing individuals reared for stock enhancement with some degree of “natural” experience prior to release. Conditioning flatfish in predator-free cages may help adjustment to the wild. From 2008–2010, the Obama Laboratory conducted pre-release, experimental cage conditioning for Japanese flounder in both the Takahama and Obama portions of Wakasa Bay, Japan. Recaptured fish were acquired through a cooperative effort between researchers and local fishermen. The objectives were to describe how characteristics of released flounder changed with cage exposure and to determine how recapture rates compared between conditioned and non-conditioned fish. Significantly more conditioned fish were recaptured than non-conditioned fish in Obama Bay in 2010 (p < 0.05). In 2008 and 2009, recapture rates of conditioned and non-conditioned flounder followed the same trend, although these were not significantly different. Laboratory experiments revealed that conditioned fish had significantly better burying abilities (p < 0.001) and enhanced feeding abilities compared to non-conditioned fish. This study is the first to examine flatfish conditioning strategies using market data and shows that cage conditioning can favorably alter the attributes and recapture rates of released fish.

Heroin-induced conditioned immunomodulation requires expression of IL-1β in the dorsal hippocampus.

Opioid-associated environmental stimuli elicit robust immune-altering effects via stimulation of a neural circuitry that includes the basolateral amygdala and nucleus accumbens. These brain regions are known to have both direct and indirect connections with the hippocampus. Thus, the present study evaluated whether the dorsal hippocampus (DH), and more specifically interleukin-1 beta (IL-1β) within the DH, is necessary for the expression of heroin-induced conditioned immunomodulation. Rats received five Pavlovian pairings of systemic heroin administration (1.0mg/kg, SC) with placement into a distinct environment (conditioned stimulus, CS). Six days after conditioning, a GABAA/B agonist cocktail or IL-1β small interfering RNA (siRNA) was microinfused into the DH to inhibit neuronal activity or IL-1β gene expression prior to CS or home cage exposure. Control animals received saline or negative control siRNA microinfusions. Furthermore, all rats received systemic administration of lipopolysaccharide (LPS) to stimulate proinflammatory nitric oxide production. CS exposure suppressed LPS-induced nitric oxide production relative to home cage exposure. Inactivation of, or IL-1β silencing in, the DH disrupted the CS-induced suppression of nitric oxide production relative to vehicle or negative control siRNA treatment. These results are the first to show a role for DH IL-1β expression in heroin-conditioned suppression of a proinflammatory immune response.

Structural and Electrical Myocardial Remodeling in a Rodent Model of Depression

Despite a well-documented association between stress and depression with cardiac morbidity and mortality, there is no satisfactory explanation for the mechanisms linking affective and cardiac disorders. This study investigated cardiac electrophysiological properties in an animal model of depression. Depression-relevant physiological and behavioral parameters were measured in adult male wild-type rats during and after a period of intermittent social defeat stress (n = 12) or empty cage exposure (control, n = 11). Nine days after the last defeat/empty cage exposure, high-definition epicardial mapping was performed under anesthesia. Stressed animals versus controls displayed a larger reduction in the circadian amplitude of heart rate (-32% [3%] versus -13 [2%]; p = .001) and body temperature (-33% [4%] versus -5% [2%]; p = .001) rhythms, had smaller body weight gain (+11% [1%] versus +17% [1%]; p < .001), and showed a larger reduction in sucrose solution intake (-19% [6%] versus -7% [4%]; p = .006). Epicardial mapping analysis revealed a decrease in the transversal conduction velocity of the wavefront (0.23 [0.0] versus 0.27 [0.1] m/s; p = .02) and a shortening of the effective refractory period (86.8 [2.1] versus 95.9 [3.0] milliseconds; p = .01) in stressed animals. Upon killing, moderate left ventricular fibrosis was observed in the stressed group. Intermittent social stress procedure is associated with depression-like symptoms and altered myocardial electrical stability in a potentially proarrhythmic manner. In particular, reduced myocardial refractoriness and impaired conduction, which are considered major determinants of arrhythmogenesis, represent possible mechanisms underlying cardiac vulnerability.

Social status alters defeat-induced neural activation in Syrian hamsters

Although exposure to social stress leads to increased depression-like and anxiety-like behavior, some individuals are more vulnerable than others to these stress-induced changes in behavior. Prior social experience is one factor that can modulate how individuals respond to stressful events. In this study, we investigated whether experience-dependent resistance to the behavioral consequences of social defeat was associated with a specific pattern of neural activation. We paired weight-matched male Syrian hamsters in daily aggressive encounters for 2 weeks, during which they formed a stable dominance relationship. We also included control animals that were exposed to an empty cage each day for 2 weeks. Twenty-four hours after the final pairing or empty cage exposure, half of the subjects were socially defeated in 3, 5-min encounters, whereas the others were not socially defeated. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains after social defeat and processed the tissue for c-Fos immunoreactivity. We found that dominants were more likely than subordinates to counter-attack the resident aggressor during social defeat, and they showed less submissive and defensive behavior at conditioned defeat testing compared with subordinates. Also, social status was associated with distinct patterns of defeat-induced neural activation in select brain regions, including the amygdala, prefrontal cortex, hypothalamus, and lateral septum. Our results indicate that social status is an important form of prior experience that predicts both initial coping style and the degree of resistance to social defeat. Further, the differences in defeat-induced neural activation suggest possible brain regions that may control resistance to conditioned defeat in dominant individuals.

Integrated assessment of biomarker responses in caged shrimps (Litopenaeus vannamei) exposed to complex contaminants from the Maluan Bay of China

The marine shrimp Litopenaeus vannamei were used as an active biomonitoring organism to assess the bioavailability and impact of metal contaminants in seven study sites along the Maluan Bay of China. Metal concentrations in the hepatopancreas of shrimps were determined in conjunction with four biomarkers responses after a 7 day in situ cage exposures. The results showed that contaminant tissue burdens at the deployment sites were greater than those of the reference site, and antioxidant enzyme activities were strongly inhibited compared to those of reference organisms. Variations in these biomarker responses were correlated significantly (p < 0.05 or p < 0.01) with the specific metal pollutants at the study sites, but no significant correlations existed between catalase activity responses and the metal contaminants. This suggests the presence of undetermined contaminants or other exposure routes that may be responsible for the decreased catalase activity. Multivariate analysis revealed a causal relationship between contaminants at each deployment site and the biochemical "response" of the caged shrimps at these sites and demonstrated the presence of two contaminant "hot" spots. This investigation suggested that the incorporation of chemical data on trace metal concentrations with the analysis of antioxidant enzymatic activities in caged shrimps can be a useful tool for the identification of causal toxic contaminants in complex mixtures.

Incorporation of in situ exposure and biomarkers response in clams Ruditapes philippinarum for assessment of metal pollution in coastal areas from the Maluan Bay of China

The clams Ruditapes philippinarum were used to assess the impact of metal contaminants when transplanted to seven study sites along the Maluan Bay (China). Metal concentrations in digestive gland tissues of clams after 7-day in situ cage exposure were determined in conjunction with antioxidant enzyme activities. The results showed the importance of specific antioxidant biomarkers to assess complex pollutant mixtures and their good correlations to the pollutant compositions of deployment sites. Multivariate analysis indicated causal relationship between the chemicals at each study site and the biochemical “response” of the caged clams at these sites and demonstrated the potential presence of two different contaminant sources. This study suggested that the incorporation of tissue residue analysis with biomarkers response in caged clams together with factor analysis can be a useful biomonitoring tool for the identification of causal toxic pollutants and the assessment of complex metal pollutions in marine coastal environment.

Physiological and hormonal responses to novelty exposure in rats are mainly related to ongoing behavioral activity

Stress research has been dominated by a circular type of reasoning that occurrence of a stress response is bad. Consequently, the stimulus is often interpreted as stressful in terms of aversiveness involving uncontrollability and unpredictability, which may have maladaptive and pathological consequences. However, the hypothalamic–pituitary–adrenal (HPA) axis and sympathico-adrenomedullary (SAM) system are not only activated in response of the organism to challenges, but also prepare and support the body for behavior. Therefore, a considerable part of the physiological and hormonal responses to a certain situation can be a direct reflection of the metabolic requirements for the normal ongoing behavioral activity, rather than of the stressful nature. In order to clarify this, behavioral, physiological, hormonal and electroencephalographic (EEG) responses to novel cage exposure were studied in male Sprague–Dawley rats. Forced confrontation with a novel cage has been interpreted as a psychological and aversive stressor. However, this interpretation is simply based on the occurrence of a stress response. This study aimed at detailed analysis of the time course of the novelty-induced responses. Different parameters were measured simultaneously in freely moving rats, which allowed correlational comparisons. Hereto, radio telemetry using a small implantable transmitter combined with permanent catheters and an automated blood sampling system was used. A camera placed above the cage allowed behavioral observations. The results show that novelty exposure induced significant increases in locomotor activity, heart rate, blood pressure and plasma corticosterone together with a complete lack of sleep as compared to the undisturbed control situation. The latency to reach significance and the duration of responses varied across parameters but all had recovered within 30min after termination of novelty. The behavioral activity (locomotor activity and EEG wakefulness duration) response pattern was significantly correlated with that of heart rate, blood pressure and plasma corticosterone. Behavioral observations showed mainly explorative behavior in response to novelty. Therefore, the present results indicate that the novelty-induced physiological and hormonal responses are closely related to the ongoing, mainly explorative behavioral activity induced by novelty. An interpretation in terms of metabolic support of ongoing behavior seems to be more appropriate than the frequently used stress interpretation. The present study also emphasizes the added value of simultaneous assessment of behavioral, physiological and hormonal parameters under controlled, non-confounding conditions.

Effects of dominance status on conditioned defeat and expression of 5-HT1A and 5-HT2A receptors

Past experience can alter how individuals respond to stressful events. The brain serotonin system is a key factor modulating stress-related behavior and may contribute to individual variation in coping styles. In this study we investigated whether dominant and subordinate hamsters respond differently to social defeat and whether their behavioral responses are associated with changes in 5-HT1A and 5-HT2A receptor immunoreactivity in several limbic brain regions. We paired weight-matched hamsters in daily aggressive encounters for two weeks so that they formed a stable dominance relationship. We also included controls that were exposed to an empty cage each day for two weeks. Twenty-four hours after the final pairing or empty cage exposure, subjects were socially defeated in 3, 5-min encounters with a more aggressive hamster. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains following conditioned defeat testing and performed immunohistochemistry for 5-HT1A and 5-HT2A receptors. We found that dominants showed less submissive and defensive behavior at conditioned defeat testing compared to both subordinates and controls. Additionally, both dominants and subordinates had an increased number of 5-HT1A immunopositive cells in the basolateral amygdala compared to controls. Subordinates also had more 5-HT1A immunopositive cells in the dorsal medial amygdala than did controls. Finally, dominants had fewer 5-HT1A immunopositive cells in the paraventricular nucleus of the hypothalamus compared to controls. Our results indicate that dominant social status results in a blunted conditioned defeat response and a distinct pattern of 5-HT1A receptor expression, which may contribute to resistance to conditioned defeat.

Continuous stress disrupts immunostimulatory effects of IL-12

Immune stimulation by biological response modifiers is a common approach in tumor immunotherapy. IL-12 was found effective in various animal studies, but clinical trials showed limited success. However, among other differences, animal models do not simulate psychological or physiological stress while employing IL-12, whereas cancer patients often experience distress while treated with immunostimulants. Thus, in the current study we assessed the impact of continuous stress on the efficacy of IL-12 immunostimulation. F344 rats were subjected to a pharmacological stress paradigm (continuous administration of a β-adrenergic agonist) or to a 20h behavioral stress paradigm (wet cage exposure) commencing 2h before IL-12 administration. Twenty-six hours after stress initiation, we studied indices known to reflect IL-12 immunostimulatory impacts, including NK cell numbers and activity in different immune compartments, and in vivo resistance to MADB106 lung tumor colonization. The results indicated that both the pharmacological and behavioral stress paradigms significantly reduced the increase in the number and activity of marginating-pulmonary NK cells evident in non-stressed IL-12 treated animals. Additionally, stressed animals exhibited a lower IL-12-induced improvement of MADB106 lung clearance, an in vivo index that markedly depends on total marginating-pulmonary NK activity. These deleterious effects of stress were more prominent in males than in females. Overall, the findings demonstrate that prolonged stress exposure can disrupt the efficacy of simultaneous immunostimulatory treatments, irrespective of stress effects on baseline immune measures. Neuroendocrine and cellular mediating mechanisms are yet unknown, but the potential clinical ramifications of these findings warrant consideration in clinical trials employing immunostimulatory agents.