Effect of anticancer drugs on the release of interleukin-6 in vitro

Summary This study investigates the effects of anticancer drugs and immunomodulating agents on the release of interleukin-6 (IL-6) from lipopolysaccharide-stimulated human peripheral blood mononuclear leucocytes in vitro. The addition of non-cytotoxic concentrations of Adriamycin (doxorubicin), vincristine and 4-OOH-cyclophosphamide (the in vitro active analogue of cyclophosphamide) resulted in suppression of IL-6 release. The drugs bleomycin, FK156 [d-lactoyl-l-alanyl--d-glutamyl-(l)-meso-diaminopimelyl-(l)-glycine], FK565 [heptanoyl--d-glutamyl-(l)-meso-diaminopimelyl-(d)-alanine] and the immunosuppressive agent cyclosporin A did not alter the release of IL-6 in the same experimental system.     

Identification and characterization of functional intermediates of stem bromelain during urea and guanidine hydrochloride unfolding

By comparing changes in enzyme activity with changes in spectral features for stem bromelain (EC.3.4.22.32) in the absence and presence of urea, Guanidine hydrochloride and ethanol; four intermediate states could be identified: two activity-enhanced state obtained in the presence of 5 M urea and 2 M GnHCl, termed X and X', respectively, and a third, similarly active state closely resembling the native protein in the presence of 8-9 M urea, termed Y. The enhanced activity of these states is due to local conformational changes accompanied by increased dynamics in the active site. Further, the enzyme does not lose its activity after substantial tertiary structure changes in 8-9 M urea (Y state), suggesting that active site containing domain is more resistant to chemical denaturation than the other structural domain. This makes stem bromelain and in general cysteine proteases an exception to the hypothesis that active site is the most labile part of enzyme.     

The climate of the Younger Dryas as a boundary for Einkorn domestication

The domestication of the Neolithic founder crops of the Near East has recently been a topic of debate particularly with respect to how rapidly the domestication of these crops occurred. One school of thought maintains that these processes lasted several thousand years (‘protracted model’ with ‘gathering’, ‘cultivation’ and ‘domestication’ as three stages of a continuum, each taking up to several thousand years), while another favors the view that domestication occurred much more quickly, over several hundred years at most (‘rapid transition’). Our study focuses on one of these crops, 1-grained domesticated Einkorn wheat, incorporating data from geology, vegetation history, and climate. In the Karacadağ region of southeastern Turkey, where 1-grained Einkorn wheat was domesticated, the climate was severe (i.e. cold and dry) during the Younger Dryas. The climate of the Younger Dryas acted as boundary during which a) conditions were not suitable for ‘cultivation’, and b) Einkorn would have retreated to refugia exhibiting more suitable moisture-bearing soils that would have made ‘gathering’ difficult. Around 11600 cal. b.p., the Younger Dryas ended and a very rapid climatic amelioration commenced at the beginning of the Early Holocene, enabling grasses to spread throughout the region. A ritual PPNA/PPNB site (G?bekli Tepe) and associated PPNB settlements such as Nevali ?ori and ?ay?nü were established at this time. In the settlements of Nevali ?ori and Cafer H?yük, the oldest domesticated Einkorn was found in the earliest archaeological layers. This confirms that the inhabitants made use of domesticated 1-grained Einkorn from the very beginning of settlement activity, although they continued to practice a mixed lifestyle as hunter-gatherers and farmers. For ?ay?nü the issue is more complex, but here domesticated Einkorn also appears around the same time. In summary, by 10400 cal. b.p. domesticated 1-grained Einkorn was present in large quantities at a variety of sites. This would give a maximum window of time lasting approximately 1,200 years and is therefore not in agreement with the ‘protracted’ model but would be consistent with a ‘rapid transition’. It is improbable that the ‘cultivation’ of wild Einkorn was practiced in the Karacadağ region, since wild Einkorn was plentiful during the favorable growing conditions following the Younger Dryas, making it more likely that ‘gathering’ would have been practiced. Because Einkorn has not been found in early settlements in the southern Levant, this crop cannot have been ‘gathered’ and ‘cultivated’ there but instead was ‘domesticated’ independently and solely in southeastern Turkey. Therefore, the YD acts as a boundary, providing a maximum time frame for 1-grained Einkorn domestication.     

In-vitro and In-vivo management of Meloidogyne incognita (Kofoid and White) Chitwood and Rhizoctonia bataticola (Taub.) Butler in cotton using organic’s

Root-knot nematodes Meloidogyne incognita (Kofoid and White) Chitwood and Rhizoctonia bataticola (Taub.) Butler, fungus, are very dangerous root damaging pathogens. Present study was planned to establish a chemical control of these root deteriorating pathogens under lab conditions as well as in field. Maximum death rate of nematode juveniles and minimum numbers of nematode eggs hatched were recorded in plates treated with Cadusafos (Rugby® 100G) @12 g/100 ml and Cartap® (4% G) @9g/100 ml. Chemical treatment of Rhizoctonia bataticola with Trifloxystrobin + Tebuconazole (Nativo®) @0.2 g/100 ml and Mancozeb + Matalaxyl (Axiom) @0.25 g/100 ml significantly controlled the mycelial growth in plates. The best treatments tested in laboratory were applied in field as protective and curative treatments. Results proved that chemical control of root-knot nematode and root rot fungi by tested chemicals at recommended time and dose is a significant management technique under field conditions.     

Screening of antimicrobial,antioxidant, antidiabetic activities,anatomical and morphological properties of Colchicum speciosum Steven (Colchicaceae)

Protoplasma - Colchicum speciosum Steven species is a perennial stemless plant. C. speciosum is a flowering herb native to mountainous regions of northern Turkey, the Caucasus, and northern Iran....     

Effects of providing dietary wood (oak) charcoal to broiler chicks and laying hens

Three experiments were carried out to determine whether dietary wood (oak) charcoal applied during entire or phase feeding period would affect growth performance, abdominal fat weight, carcass weight, carcass yield, carcass composition and nutrient excretion of broilers and to determine whether dietary wood charcoal supplementation would affect laying performance and egg quality of laying hens. In the first experiment, different inclusion levels (0, 25, 50 and 100 g/kg feed) of wood charcoal in the diet were examined for a 6-week-period using broiler chicks of initial age 1 week. Dietary wood charcoal significantly increased feed intake (P<0.001), body weight gain (P<0.001) and improved feed conversion ratio (P<0.05) up to 28 days of age. However, at 49 days of age, charcoal inclusion did not significantly (P>0.05) affect body weight gain, feed intake, carcass weight and carcass yield, but increased (P<0.05) feed conversion ratio, carcass ash content, fat excretion, while reducing (P<0.05) mineral excretion in a dose dependent manner. In the second experiment, a phase application of dietary wood charcoal for a 6-week-period broiler chicks of initial age 1 week was assessed. During the first 28 days of age wood charcoal improved feed conversion ratio significantly (P<0.05). At 49 days of age, the groups receiving charcoal in the starter and/or finisher diets showed significantly (P<0.05) higher body weight gain and carcass weight than the control group receiving no charcoal. In the third experiment, different levels (0, 10, 20 and 40 g/kg feed) of wood charcoal supplementation to a layer diet were examined for a 7-week-period using laying hens of initial age 34 weeks. Dietary charcoal supplementation did not have a significant effect on any parameters related to performance and egg quality, but significantly reduced number of cracked eggs and the reduction was dose dependent (P<0.01). These data demonstrate that wood charcoal inclusion to the diet could be of value in improving broiler performance during the first 28 days of fattening period. In later ages, the positive effects of wood charcoal are limited. However, in laying hens dietary supplementation of wood charcoal reduces number of cracked eggs.     

Post-Discharge Mortality in Children with Severe Malnutrition and Pneumonia in Bangladesh

Background

Post-discharge mortality among children with severe illness in resource-limited settings is under-recognized and there are limited data. We evaluated post-discharge mortality in a recently reported cohort of children with severe malnutrition and pneumonia, and identified characteristics associated with an increased risk of death.

Methods

Young children (<5 years of age) with severe malnutrition (WHO criteria) and radiographic pneumonia on admission to Dhaka Hospital of icddr,b over a 15-month period were managed according to standard protocols. Those discharged were followed-up and survival status at 12 weeks post-discharge was determined. Verbal autopsy was requested from families of those that died.

Results

Of 405 children hospitalized with severe malnutrition and pneumonia, 369 (median age, 10 months) were discharged alive with a follow-up plan. Of these, 32 (8.7%) died in the community within 3 months of discharge: median 22 (IQR 9–35) days from discharge to death. Most deaths were reportedly associated with acute onset of new respiratory or gastrointestinal symptoms. Those that died following discharge were significantly younger (median 6 [IQR 3,12] months) and more severely malnourished, on admission and on discharge, than those that survived. Bivariate analysis found that severe wasting on admission (OR 3.64, 95% CI 1.66–7.97) and age <12 months (OR 2.54, 95% CI 1.1–8.8) were significantly associated with post-discharge death. Of those that died in the community, none had attended a scheduled follow-up and care-seeking from a traditional healer was more common (p<0.001) compared to those who survived.

Conclusion and Significance

Post-discharge mortality was common in Bangladeshi children following inpatient care for severe malnutrition and pneumonia. The underlying contributing factors require a better understanding to inform the potential of interventions that could improve survival.     

Effect of 28-homobrassinolide on the drought stress-induced changes in photosynthesis and antioxidant system of <Emphasis Type="Italic">Brassica juncea</Emphasis> L.

To investigate the effect of exogenously applied 28-homobrassinolide (HBL) on drought-stressed plants, photosynthesis and antioxidant systems were examined in Indian mustard (Brassica juncea L.). Seedlings of Indian mustard were subjected to drought stress for 7 days at the 8–14 (DS1)/15–21 (DS2) days’ stage of growth and then returned to normal conditions of growth. These seedlings were sprayed with HBL (0.01 μM) at the 30-day stage and were sampled at 60 days to assess the changes in growth, photosynthesis and antioxidant enzymes. Plants exposed to stress at either of the stages of growth exhibited a significant decrease in growth and photosynthesis. The exposure of plants to stress at an earlier stage (DS1) was more inhibitory than that at a later stage (DS2). However, the follow-up treatment with HBL significantly improved the values of these parameters and also overcame the inhibitory effect of water stress. The activity of antioxidant enzymes [catalase (E.C. 1.11.1.6), peroxidase (E.C. 1.11.1.7) and superoxide dismutase (E.C. 1.15.1.1)] and proline content in leaves exhibited an increase in response to both the treatment factors, where their interaction had an additive effect. It was, therefore, concluded that the elevated antioxidant system, at least in part, was responsible for amelioration of the drought stress.     

Diffusion Tensor Imaging and Decision Making in Cocaine Dependence

Background

Chronic stimulant abuse is associated with both impairment in decision making and structural abnormalities in brain gray and white matter. Recent data suggest these structural abnormalities may be related to functional impairment in important behavioral processes.

Methodology/Principal Findings

In 15 cocaine-dependent and 18 control subjects, we examined relationships between decision-making performance on the Iowa Gambling Task (IGT) and white matter integrity as measured by diffusion tensor imaging (DTI). Whole brain voxelwise analyses showed that, relative to controls, the cocaine group had lower fractional anisotropy (FA) and higher mean of the second and third eigenvalues (λ⊥) in frontal and parietal white matter regions and the corpus callosum. Cocaine subjects showed worse performance on the IGT, notably over the last 40 trials. Importantly, FA and λ⊥ values in these regions showed a significant relationship with IGT performance on the last 40 trials.

Conclusions

Compromised white matter integrity in cocaine dependence may be related to functional impairments in decision making.     

Surfactant protein A (SP-A)-mediated clearance of Staphylococcus aureus involves binding of SP-A to the staphylococcal adhesin eap and the macrophage receptors SP-A receptor 210 and scavenger receptor class A

Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap(+)) but not Eap-deficient (Eap(-)) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap(+) S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly, WT mice cleared infection with Eap(+) but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap(+) S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap(-) S. aureus was impaired. Macrophages express two isoforms: SP-R210(L) and SP-R210(S). The results show that WT alveolar macrophages are distinguished by expression of SP-R210(L), whereas SR-A(-/-) alveolar macrophages are deficient in SP-R210(L) expressing only SP-R210(S). Accordingly, SR-A(-/-) mice were highly susceptible to both Eap(+) and Eap(-) S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210(L) mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A.