Information parasitism in foraging Bar-tailed Godwits Limosa lapponica

Foraging behaviour of sympatric Bar-tailed Godwits Limosa lapponica and Whimbrels Numenius phaeopus was studied in the period prior to egg-laying. Godwit females preferred wet bogs, while godwit males and Whimbrels foraged on dry palsas in the bogs. Habitat overlap between godwit males and Whimbrels was larger than intersexual overlap in the godwits. Observations of scanning behaviour of foraging godwits showed that the vigilance level of males was not affected by the presence or absence of their mates. Female vigilance levels, however, dropped significantly when females fed near their mate, and—in the absence of the mate—near Whimbrels. While female godwits benefited from associating with Whimbrels, males seemed to avoid close proximity to this species. Whimbrels chased godwit males more often than females, presumably because they used the same foraging habitats.     

Exertional myopathy in pileated woodpeckers (Dryocopus pileatus) subsequent to capture

Out of 33 Pileated Woodpeckers (Dryocopus pileatus) captured and fitted with radio-transmitters, 12 were later found dead. Three carcasses were recovered and submitted for necropsy. One bird had large pale foci in multiple muscles. Microscopically, skeletal muscle in all three had evidence of severe coagulative necrosis, consistent with capture myopathy.     

Movements and Conflicts in a Flock of Foraging Black‐Tailed Godwits (Limosa limosa): The Influence of Feeding Rates on Behavioural Decisions

We studied movements and conflicts within a small flock of free‐living black‐tailed godwits foraging on benthic invertebrates in a brackish lagoon. To interpret our results in the framework of foraging theory, we studied the influence of individual feeding rate on the decisions to move and to attack flock companions. Birds changed their position within the flock more often when their intake rate was low and sometimes attacked conspecifics to supplant them from their feeding place. Aggressors significantly avoided front attacks and were almost always successful. They attacked individuals having higher feeding rates than themselves and their own feeding rate significantly increased after the attack, although victims were not chased off to particularly poor sites. Our results suggest that aggressors could obtain reliable information about the quality of the foraging site they coveted by observing their victim’s feeding activity before attacking. Although aggression seemed to be caused by a low intake rate, we show that displacing another bird was more time‐consuming than independent foraging. We conclude that it was not the most profitable behaviour in terms of energy intake. Foraging site displacement probably also had social functions, such as reinforcement of social status in a flock of birds preparing for pre‐breeding migration.     

Biodistribution of sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) in an oral cancer model

Boron neutron capture therapy (BNCT) is based on selective accumulation of ¹⁰B carriers in tumor followed by neutron irradiation. We previously proved the therapeutic success of BNCT mediated by the boron compounds boronophenylalanine and sodium decahydrodecaborate (GB-10) in the hamster cheek pouch oral cancer model. Based on the clinical relevance of the boron carrier sodium borocaptate (BSH) and the knowledge that the most effective way to optimize BNCT is to improve tumor boron targeting, the specific aim of this study was to perform biodistribution studies of BSH in the hamster cheek pouch oral cancer model and evaluate the feasibility of BNCT mediated by BSH at nuclear reactor RA-3. The general aim of these studies is to contribute to the knowledge of BNCT radiobiology and optimize BNCT for head and neck cancer. Sodium borocaptate (50 mg ¹⁰B/kg) was administered to tumor-bearing hamsters. Groups of 3–5 animals were killed humanely at nine time-points, 3–12 h post-administration. Samples of blood, tumor, precancerous pouch tissue, normal pouch tissue and other clinically relevant normal tissues were processed for boron measurement by optic emission spectroscopy. Tumor boron concentration peaked to therapeutically useful boron concentration values of 24–35 ppm. The boron concentration ratio tumor/normal pouch tissue ranged from 1.1 to 1.8. Pharmacokinetic curves showed that the optimum interval between BSH administration and neutron irradiation was 7–11 h. It is concluded that BNCT mediated by BSH at nuclear reactor RA-3 would be feasible.     

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT, boronophenylalanine (BPA) + neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA-BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks post-treatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA-BNCT, 2.7 ± 1.8 for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mg fell significantly to 19 ± 16 mg for BPA-BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA-BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA-BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.     

Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers

Neoplastic growth and dissemination involve increased proteolytic activity that is able to escape the regulative elements. Matrix metalloproteinases (MMPs), particularly gelatinases A and B (MMP-2 and -9), play a role in tumor invasion and angiogenesis, and they participate in cancer progression in several neoplasias. The expression of tissue inhibitors of gelatinases, TIMPs-1 and -2, has also been shown to be associated with the clinical course in some cancers. The prognostic value of these markers, however, seems to vary a great deal in different neoplastic diseases. In this review, the impact of the gelatinases and their inhibitors on the clinical course in several solid cancers is evaluated based on the growing data from recent clinical studies. The clinical data most often explore the overexpression of mRNA or immunoreactive protein in tumor tissue, or measure the concentration of the circulating proteinase or its inhibitor in pretreatment or follow-up serum samples. The growing amount of recent clinical data suggests that the impact of gelatinases on treatment decisions should be tested in clinical trials.     

The plant-based immunomodulator curcumin as a potential candidate for the development of an adjunctive therapy for cerebral malaria

The clinical manifestations of cerebral malaria (CM) are well correlated with underlying major pathophysiological events occurring during an acute malaria infection, the most important of which, is the adherence of parasitized erythrocytes to endothelial cells ultimately leading to sequestration and obstruction of brain capillaries. The consequent reduction in blood flow, leads to cerebral hypoxia, localized inflammation and release of neurotoxic molecules and inflammatory cytokines by the endothelium. The pharmacological regulation of these immunopathological processes by immunomodulatory molecules may potentially benefit the management of this severe complication. Adjunctive therapy of CM patients with an appropriate immunomodulatory compound possessing even moderate anti-malarial activity with the capacity to down regulate excess production of proinflammatory cytokines and expression of adhesion molecules, could potentially reverse cytoadherence, improve survival and prevent neurological sequelae. Current major drug discovery programmes are mainly focused on novel parasite targets and mechanisms of action. However, the discovery of compounds targeting the host remains a largely unexplored but attractive area of drug discovery research for the treatment of CM. This review discusses the properties of the plant immune-modifier curcumin and its potential as an adjunctive therapy for the management of this complication.     

微生态制剂辅助治疗婴儿巨细胞病毒肝炎的疗效观察

目的观察微生态制剂辅助治疗婴儿巨细胞病毒肝炎的疗效。方法巨细胞病毒肝炎婴儿74例,随机分为2组。对照组给予常规保肝治疗;治疗组给予常规治疗+乐托尔1粒Bid口服。疗程2周,比较TB(总胆红素)、DB(结合胆红素)、ALT(谷丙转氨酶)和AST(谷草转氨酶)变化。结果治疗组TB、DB和AST较对照组明显降低(P<0.05)。结论微生态制剂辅助治疗婴儿巨细胞病毒肝炎有一定的疗效。     

The plant-based immunomodulator curcumin as a potential candidate for the development of an adjunctive therapy for cerebral malaria

Background

Considering the natural history of malaria of continued susceptibility to infection and episodes of illness that decline in frequency and severity over time, studies which attempt to relate immune response to protection must be longitudinal and have clearly specified definitions of immune status. Putative vaccines are expected to protect against infection, mild or severe disease or reduce transmission, but so far it has not been easy to clearly establish what constitutes protective immunity or how this develops naturally, especially among the affected target groups. The present study was done in under six year old children to identify malaria antigens which induce antibodies that correlate with protection from Plasmodium falciparum malaria.

Methods

In this longitudinal study, the multiplex assay was used to measure IgG antibody levels to 10 malaria antigens (GLURP R0, GLURP R2, MSP3 FVO, AMA1 FVO, AMA1 LR32, AMA1 3D7, MSP1 3D7, MSP1 FVO, LSA-1and EBA175RII) in 325 children aged 1 to 6 years in the Kassena Nankana district of northern Ghana. The antigen specific antibody levels were then related to the risk of clinical malaria over the ensuing year using a negative binomial regression model.

Results

IgG levels generally increased with age. The risk of clinical malaria decreased with increasing antibody levels. Except for FMPOII-LSA, (p = 0.05), higher IgG levels were associated with reduced risk of clinical malaria (defined as axillary temperature ≥37.5°C and parasitaemia of ≥5000 parasites/ul blood) in a univariate analysis, upon correcting for the confounding effect of age. However, in a combined multiple regression analysis, only IgG levels to MSP1-3D7 (Incidence rate ratio = 0.84, [95% C.I.= 0.73, 0.97, P = 0.02]) and AMA1 3D7 (IRR = 0.84 [95% C.I.= 0.74, 0.96, P = 0.01]) were associated with a reduced risk of clinical malaria over one year of morbidity surveillance.

Conclusion

The data from this study support the view that a multivalent vaccine involving different antigens is most likely to be more effective than a monovalent one. Functional assays, like the parasite growth inhibition assay will be necessary to confirm if these associations reflect functional roles of antibodies to MSP1-3D7 and AMA1-3D7 in this population.     

微生态制剂治疗肝源性肠道菌群失调与保肝作用

目的:观察采用常规保肝治疗及或加服乐托尔或加服培菲康来治疗慢性肝病疗效.方法:慢迁肝41例及慢活肝37例,各随机分成三组:A组:常规治疗 乐托尔胶囊,2粒/次,2次/d;B组:常规治疗 培菲康胶囊,3粒/次,3次/d;C组:常规治疗:益肝灵 Vit.C Vit.B Co,各2片/次,3次/d,三组疗程均为2个月.结果:75例完成治疗及复查,失访3例.腹胀、腹泻、肝区不适消失率及ALT、内毒素试验复常率二项三组相比有显著意义(P<0.01).乏力、SB复常率在慢活肝中三组相比有显著意义(P<0.01).总有效率:慢迁肝三组分别为83.3%、69.2%、35.7%;慢活肝三组分别为:63.7%、61.5%、33.3%,三组相比有显著意义(P<0.01).结论:常规保肝治疗加服微生态制剂,不论是死菌及其代谢产物或活菌制剂均有肯定的价值,但死菌制剂具有活菌制剂不具备的优点.     

Decrease in feeding niche breadth of Melasoma lapponica (Coleoptera: Chrysomelidae) with increase in pollution

We studied host-plant preference and performance of the leaf beetle, Melasoma lapponica, around Severonikel smelter situated in Monchegorsk, Russia. The breadth of feeding niche (Smith's measure) based on both field counts and preference tests decreased with an increase of ambient SO₂ concentration, but showed no relationship with either metal pollutants or beetle population densities. In heavily polluted plots (mean annual SO₂ concentrations 400–1000 g/m³) the beetles concentrated on Salix borealis, Whereas in moderately and slightly polluted plots they used other willow species as well. No difference in survival was revealed between M. lapponica fed with leaves of S. borealis from heavily and sloghtly polluted plots. However, performance of larvae fed with Salix caprea and S. Phylicifolia was significantly lower when leaves were collected from heavily polluted plots. In these plots beetles clearly preferred S. borealis, the only species assuring high survival of M. lapponica under strong pollution impact. Decrease in preference of two less favourable hosts, S. caprea and S. phylicifolia, with increase in pollution can therefore be considered as an adaptive response of M. lapponica to pollution-induced changes in host-plant quality.     

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

Boron neutron capture therapy (BNCT) combines selective accumulation of (10)B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na(3) [ae-B(20)H(17)NH(3)], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.     

Hyaluronan as carrier of carboranes for tumor targeting in boron neutron capture therapy

Boron neutron capture therapy (BNCT) represents a promising approach for tumor therapy. A critical requirement for BNCT is tumor targeting, a goal that is currently addressed with the development of low and high molecular weight agents capable of interacting with receptors expressed by cancer cells. Here, we describe a new bioconjugate (HApCB) composed by n-propyl carborane linked to hyaluronan (HA) via an ester linkage for a degree of substitution of approximately 30%, leading to a water-soluble derivative. The structure and main physicochemical characteristics of the new HA derivative were determined by means of Fourier transform infrared, fluorescence, and 1H, 13C, and 10B NMR analysis and are herein reported in detail. As HA is recognized by the CD44 antigen, densely populating the surface of many tumor cells, HApCB is expected to deliver boron atoms from the locally released carborane cages directly to target cells for antitumor application in BNCT. In vitro biological experiments showed that HApCB was not toxic for a variety of human tumor cells of different histotypes, specifically interacted with CD44 as the native unconjugated HA, and underwent uptake by tumor cells, leading to accumulation of amounts of boron atoms largely exceeding those required for a successful BNCT approach. Thus, HApCB may be regarded as a promising new BNCT agent for specific targeting of cancer cells overexpressing the CD44 receptor.     

Particles of liquid-crystalline dispersions formed by (nucleic acid-rare earth element) complexes as a potential platform for neutron capture therapy

Microscopic size particles of the cholesteric double-stranded DNA (RNA) liquid-crystalline dispersions, containing the ions of the rare earth elements in their content, have been obtained for the first time. The properties of these particles differ from those of classical DNA cholesterics noticeably. The local concentration of the rare earth elements in a particle reaches 200 mg/ml. The particles of the liquid-crystalline dispersion of the (DNA-gadolinium) complex maintain the properties for a long time. The combination of the microscopic size of particles, high concentration of gadolinium in particles and their stability opens a way to practical application of this new biomaterial.     

Receptor-targeted liposomal delivery of boron-containing cholesterol mimics for boron neutron capture therapy (BNCT)

Liposomes have been a main focus of tumor-selective boron delivery strategies in boron neutron capture therapy (BNCT), a binary method for the treatment of cancer that is based on the nuclear reaction between boron atoms and low-energy thermal neutrons. Three novel carboranyl cholesterol derivatives were prepared as lipid bilayer components for the construction of nontargeted and receptor-targeted boronated liposomes for BNCT. A major structural feature of these novel boronated cholesterol mimics is the replacement of the B and the C ring of cholesterol with a carborane cluster. Computational analyses indicated that all three boronated compounds have structural features and physicochemical properties that are very similar to those of cholesterol. One of the synthesized boronated cholesterol mimics was stably incorporated into non-, folate receptor (FR)-, and vascular endothelial growth factor receptor-2 (VEGFR-2)-targeted liposomes. No major differences were found in appearance, size distribution, and lamellarity between conventional dipalmitoylphosphatidylcholine (DPPC)/cholesterol liposomes, nontargeted, and FR-targeted liposomal formulations of this carboranyl cholesterol derivative. FR-targeted boronated liposomes were taken up extensively in FR overexpressing KB cells in vitro, and the uptake was effectively blocked in the presence of free folate. In contrast, a boronated cholesterol mimic incorporated into nontargeted liposomes showed significantly lower cellular uptake. There was no apparent in vitro cytotoxicity in FR overexpressing KB cells and VEGFR-2 overexpressing 293/KDR cells when these were incubated with boronated FR- and (VEGFR-2)-targeted liposomes, respectively, although the former accumulated extensively in KB cells and the latter effectively interacted with VEGFR-2 by causing autophosphorylation and protecting 293/KDR cells from SLT (Shiga-like toxin)-VEGF cytotoxicity.     

Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model

We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.     

Rivastigmine as adjunctive therapy in the therapeutic dilemma for the treatment of hallucinations due to Parkinson disease

We report three cases of patients with Parkinson's disease without dementia, admitted to our hospital because of hallucinations. The anti-Parkinson medication was adapted and the patients started with rivastigmine. As a result, hallucinations no longer occurred. A 79 years old man also required short-term quetiapine because of agitation and anti-Parkinson doses were without side effects, as a result of which mobility improved. An 84 years old woman reported mild side effects of rivastigmine, without consequences, whereas her mobility appeared to be good. A 72 years old woman reported mild memory problems upon admission, which improved during admission, as did her mobility after increasing the anti-Parkinson medication doses. Treatment of rivastigmine can be useful in the therapeutic dilemma in the treatment of hallucinations in patients with Parkinson's disease (start anti-psychotic or reduce anti-Parkinson medication). In addition to adapting anti-Parkinson doses and sometimes short-term treating with an anti-psychotic, treatment with rivastigmine appears to be a quick improvement, without serious side effects. Also, mobility can improve, due to the possibility of increasing the anti-Parkinson doses, if necessary. Because of the many remaining questions, prospective randomised trials are needed.