Medical management of paraquat ingestion Gawarammana, Indika B.; Buckley, Nicholas A.
British journal of clinical pharmacology,
November 2011, Letnik:
72, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to inherent toxicity and lack of ...effective treatments. We conducted a systematic search for human studies that report toxicokinetics, mechanisms, clinical features, prognosis and treatment. Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12–24 h. Clinical features are largely due to intracellular effects. Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF‐κB, mitochondrial damage and apoptosis in many organs. Kinetics of distribution into these target tissues can be described by a two‐compartment model. Paraquat is actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis. Paraquat also causes renal and liver injury. Plasma paraquat concentrations, urine and plasma dithionite tests and clinical features provide a good guide to prognosis. Activated charcoal and Fuller's earth are routinely given to minimize further absorption. Gastric lavage should not be performed. Elimination methods such as haemodialysis and haemoperfusion are unlikely to change the clinical course. Immunosuppression with dexamethasone, cyclophosphamide and methylprednisolone is widely practised, but evidence for efficacy is very weak. Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti‐inflammatory and NF‐κB inhibitory actions. However, there are no published human trials. The case fatality is very high in all centres despite large variations in treatment.
Ectothermic species like fishes differ greatly in the thermal ranges they tolerate; some eurythermal species may encounter temperature ranges in excess of 25°C, whereas stenothermal species in polar ...and tropical waters live at essentially constant temperatures. Thermal specialization comes with fitness trade-offs and as temperature increases due to global warming, the physiological basis of specialization and thermal plasticity has become of great interest. Over the past 50 years, comparative physiologists have studied the physiological and molecular differences between stenothermal and eurythermal fishes. It is now well known that many stenothermal fishes have lost an inducible heat shock response (HSR). Recent advances in transcriptomics have now made it possible to examine genome-wide changes in gene expression (GE) in non-model ecologically important fish, broadening our view beyond the HSR to regulation of genes involved in hundreds of other cellular processes. Here, we review the major findings from transcriptomic studies of extreme eurythermal and stenothermal fishes in response to acute and long-term exposure to temperature, both time scales being critically important for predicting climate change responses. We consider possible molecular adaptations that underlie eurythermy and stenothermy in teleosts. Furthermore, we highlight the challenges that still face the field of comparative environmental genomics and suggest fruitful paths of future investigation.
Abstract The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway is utilized by numerous cytokines and interferons, and is essential for the development and ...function of both innate and adaptive immunity. Aberrant activation of the JAK/STAT pathway is evident in neuroinflammatory diseases such as Multiple Sclerosis and Parkinson's Disease. Innate immunity is the front line defender of the immune system and is composed of various cell types, including microglia, macrophages and neutrophils. Innate immune responses have both pathogenic and protective roles in neuroinflammation, depending on disease context and the microenvironment in the central nervous system. In this review, we discuss the role of innate immunity in the pathogenesis of neuroinflammatory diseases, how the JAK/STAT signaling pathway regulates the innate immune response, and finally, the potential for ameliorating neuroinflammation by utilization of JAK/STAT inhibitors.
Animal models and retrospective clinical data suggest that certain anaesthetic techniques can attenuate immunosuppression and minimize metastasis after cancer surgery. Natural killer (NK) T cells are ...a critical component of the anti-tumour immune response. We investigated the effect of serum from women undergoing primary breast cancer surgery, randomized to propofol–paravertebral block (PPA) or sevoflurane–opioid (GA) anaesthetic techniques, on healthy human donor NK cell function and cytotoxicity against oestrogen and progesterone receptor-positive breast cancer cells (HCC1500).
Ten subjects who donated serum before operation and 24 h after operation in an ongoing randomized prospective trial (NCT 00418457) were randomly selected. Serum from PPA (n=5) and GA (n=5) subjects was co-cultured with HCC1500 and healthy primary NK cells. NK cell activating receptors (NKp30, NKp44, NKp46, 2b4, CD16, NKG2D), cytokine production, NK CD107a expression, and cytotoxicity towards HCC1500 were examined.
Serum from PPA subjects did not alter normal NK marker expression or secretion of cytokines. Serum from GA subjects reduced NK cell activating receptor CD16 from mean (sem), 82 (2)% to 50 (4)%, P=0.001, IL-10 from 1700 (80) to 1200 (92) pg ml−1, P=0.001, and IL-1β from 68 (12) to 19 (4) pg ml−1, P=0.01. An increase in NK cell CD107a 23 (2)% to 37(3)%, P=0.007 and apoptosis of HCC1500 11 (1)% to 21 (2)%, P=0.0001 was observed with PPA serum, but not GA serum, treated NK cells.
Serum from women with breast cancer undergoing surgical excision who were randomized to receive a PPA anaesthetic technique led to greater human donor NK cell cytotoxicity in vitro compared with serum from women who received GA.
NCT 041857.
Minimal residual disease (MRD) is associated with adverse outcome in acute myeloid leukemia (AML) after myeloablative (MA) hematopoietic cell transplantation (HCT). We compared this association with ...that seen after nonmyeloablative (NMA) conditioning in 241 adults receiving NMA (n=86) or MA (n=155) HCT for AML in first remission with pre-HCT bone marrow aspirates assessed by flow cytometry. NMA patients were older and had more comorbidities and secondary leukemias. Three-year relapse estimates were 28% and 57% for MRD(neg) and MRD(pos) NMA patients, and 22% and 63% for MA patients. Three-year overall survival (OS) estimates were 48% and 41% for MRD(neg) and MRD(pos) NMA patients and 76% and 25% for MA patients. This similar OS after NMA conditioning was largely accounted for by higher non-relapse mortality (NRM) in MRD(neg) (30%) compared with MRD(pos) (10%) patients, whereas the reverse was found for MRD(neg) (7%) and MRD(pos) (23%) MA patients. A statistically significant difference between MA and NMA patients in the association of MRD with OS (P<0.001) and NRM (P=0.002) but not relapse (P=0.17) was confirmed. After adjustment, the risk of relapse was 4.51 times (P<0.001) higher for MRD(pos) patients. These data indicate that the negative impact of MRD on relapse risk is similar after NMA and MA conditioning.
We present the spectroscopic evolution of AT 2017gfo, the optical counterpart of the first binary neutron star (BNS) merger detected by LIGO and Virgo, GW170817. While models have long predicted that ...a BNS merger could produce a kilonova (KN), we have not been able to definitively test these models until now. From one day to four days after the merger, we took five spectra of AT 2017gfo before it faded away, which was possible because it was at a distance of only 39.5 Mpc in the galaxy NGC 4993. The spectra evolve from blue (∼6400 K) to red (∼3500 K) over the three days we observed. The spectra are relatively featureless-some weak features exist in our latest spectrum, but they are likely due to the host galaxy. However, a simple blackbody is not sufficient to explain our data: another source of luminosity or opacity is necessary. Predictions from simulations of KNe qualitatively match the observed spectroscopic evolution after two days past the merger, but underpredict the blue flux in our earliest spectrum. From our best-fit models, we infer that AT 2017gfo had an ejecta mass of 0.03 M , high ejecta velocities of 0.3c, and a low mass fraction ∼10−4 of high-opacity lanthanides and actinides. One possible explanation for the early excess of blue flux is that the outer ejecta is lanthanide-poor, while the inner ejecta has a higher abundance of high-opacity material. With the discovery and follow-up of this unique transient, combining gravitational-wave and electromagnetic astronomy, we have arrived in the multi-messenger era.
We have measured the orbital parameters of seven close binaries, including six new objects, in a radial velocity survey of 38 objects comprising a hot subdwarf star with orbital periods ranging from ...∼0.17 to 3 d. One new system, GALEX J2205−3141, shows reflection on an M dwarf companion. Three other objects show significant short-period variations, but their orbital parameters could not be constrained. Two systems comprising a hot subdwarf paired with a bright main-sequence/giant companion display short-period photometric variations possibly due to irradiation or stellar activity and are also short-period candidates. All except two candidates were drawn from a selection of subluminous stars in the Galaxy Evolution Explorer ultraviolet sky survey. Our new identifications also include a low-mass subdwarf B star and likely progenitor of a low-mass white dwarf (GALEX J0805−1058) paired with an unseen, possibly substellar, companion. The mass functions of the newly identified binaries imply minimum secondary masses ranging from 0.03 to 0.39 M⊙. Photometric time series suggest that, apart from GALEX J0805−1058 and J2205−3141, the companions are most likely white dwarfs. We update the binary population statistics: close to 40 per cent of hot subdwarfs have a companion. Also, we found that the secondary mass distribution shows a low-mass peak attributed to late-type dwarfs, and a higher mass peak and tail distribution attributed to white dwarfs and a few spectroscopic composites. Also, we found that the population kinematics imply an old age and include a few likely halo population members.
Water is becoming a scarce resource in many parts of South Africa and, therefore, numerous plans are being put in place to satisfy the increased urban demand for this resource. Two of the methods ...currently considered are desalination of seawater and reuse of mine-affected water based on the use of reverse osmosis (RO) membranes. Due to their high energy consumption and associated environmental impacts, these methods have been under scrutinity and, therefore, an LCA was undertaken for both methods. To allow comparison between the two, the functional unit of 1 kL of potable water was specified. Design data were collected for both the construction and operation phases of the plants while SimaPro was used as the LCA analysis software with the application of the ReCiPe Midpoint method. The results indicate that the operation phase carried a greater environmental burden than the materials required for the infrastructure. In particular, electricity production and consumption is responsible for the majority of environmental impacts that stem from the respective plants. The total energy consumption of the proposed desalination plant is 3.69 kWh/kL and 2.16 kWh/kL for the mine-water reclamation plant. This results in 4.17 kg CO2 eq/kL being emitted for the desalination plant and 2.44 kg CO2 eq/kL for the mine-affected plant. A further analysis indicated that replacing South African electricity with photovoltaic (solar) and wind power has the potential to bring significant environmental benefits. The integration of these renewable energy systems with desalination and membrane treatment of mine-affected water has been proven to reduce environmental burdens to levels associated with conventional water technologies powered by the current electricity mix.
Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection ...methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (hazard ratio=2.76 1.90-4.00), overall survival (hazard ratio=2.36 1.73-3.22), and cumulative incidence of relapse (hazard ratio=3.65 2.53-5.27), but not non-relapse mortality (hazard ratio=1.12 0.81-1.55). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than
polymerase chain reaction-based detection (I
=75.1%
<0.1% for leukemia-free survival, 67.8%
<0.1% for overall survival, and 22.1%
<0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation.
Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV ...envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites.
We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming.
There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range IQR:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1-2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0-4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85-1.0) and no biomarker performed better than sCr at later time points.
sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.
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