ABSTRACT
Effects of 18% thinning on nutrient fluxes were investigated in a broadleaf forest. Streamflow and suspended sediment were sampled during the calibration and treatment periods for the treatment and control watersheds to determine total nutrient fluxes through bedload sediment and runoff. Streamflow was measured, and water samples were collected from the streams of the watersheds. The volume of the bedload deposited in both weirs' pools was measured, and sediment deposits were sampled at the ends of the calibration and treatment periods. Water and sediment samples were analyzed for calcium (Ca2+ ), magnesium (Mg2+ ), Kjeldahl nitrogen (KN), sodium (Na+ ), potassium (K+ ), iron (Fe3+ ), and sulfur (S2- ). Results showed that there was only a significant increase in KN loss from 0.01 kg/ha to 0.10 kg/ha and from 0.04 kg/ha to 2.41 kg/ha in the second and the third post-treatment years, respectively (P < 0.05). Thinning was not intensive to change nutrient outflow in the study site. PRACTITIONER POINTS: The 18% thinning was not intensive enough to increase the total nutrient flux, deteriorate water chemical quality, and hence threaten aquatic life in the stream water. Significant increases were found only in KN outflow after timber removal. If there is no information about the effect of timber harvest on nutrient loss in a specific watershed, the application of evenly distributed low-intensity timber harvest may be a good option to protect stream water quality in forested watersheds. Further investigations are needed about the effects of various timber harvest intensities on physical water quality (odor, color, turbidity, taste, temperature, etc.) and biological characteristics (population and biodiversity of aquatic organisms) of the stream water for making better water management plans.
Subject(s)
Forests , Fresh Water , Nitrogen/analysis , Nutrients , Water QualityABSTRACT
The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.
Subject(s)
Allopurinol/toxicity , Drug Hypersensitivity/etiology , Gout/drug therapy , Multiple Organ Failure/chemically induced , Stevens-Johnson Syndrome/etiology , Aged , Diagnosis, Differential , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/therapy , Fatal Outcome , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Male , Multiple Organ Failure/diagnosis , Multiple Organ Failure/therapy , Recurrence , Stevens-Johnson Syndrome/diagnosis , Stevens-Johnson Syndrome/therapyABSTRACT
Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. Ajulemic acid and HU210 are non-psychotropic, synthetic cannabinoids. Cannabidiol is a non-psychotropic plant constituent of cannabis sativa. There are hints that non-cannabinoid receptor mechanisms of these cannabinoids might be mediated via glycine receptors. In this study, we investigated the impact of the amino acid residue serine at position 267 on the glycine-modulatory effects of ajulemic acid, cannabidiol and HU210. Mutated alpha(1)S267I glycine receptors transiently expressed in HEK293 cells were studied by utilising the whole-cell clamp technique. The mutation of the alpha(1) subunit TM2 serine residue to isoleucine abolished the co-activation and the direct activation of the glycine receptor by the investigated cannabinoids. The nature of the TM2 (267) residue of the glycine alpha(1) subunit is crucial for the glycine-modulatory effect of ajulemic acid, cannabidiol and HU210. An investigation of the impact of such mutations on the in vivo interaction of cannabinoids with glycine receptors should permit a better understanding of the molecular determinants of action of cannabinoids.
Subject(s)
Cannabidiol/pharmacology , Dronabinol/analogs & derivatives , Receptors, Glycine/drug effects , Allosteric Regulation/drug effects , Amino Acid Sequence , Cell Line , Dronabinol/pharmacology , Humans , Mutation , Patch-Clamp Techniques , Receptors, Glycine/genetics , Receptors, Glycine/metabolismABSTRACT
Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. HU210 is a non-psychotropic, synthetic cannabinoid. As we hypothesized that non-CB receptor mechanisms of HU210 might contribute to its anti-inflammatory and anti-nociceptive effects we investigated the interaction of HU210 with strychnine-sensitive alpha(1 )glycine receptors by using the whole-cell patch clamp technique. HU210 showed a positive allosteric modulating effect in a low micromolar concentration range (EC(50): 5.1 +/- 2.6 micromol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 micromol/l (EC(50): 188.7 +/- 46.2 micromol/l). These in vitro results suggest that strychnine-sensitive glycine receptors may be a target for HU210 mediating some of its anti-inflammatory and anti-nociceptive properties.
Subject(s)
Allosteric Regulation/drug effects , Dronabinol/analogs & derivatives , Membrane Potentials/drug effects , Receptors, Glycine/agonists , Cell Line, Transformed , Dronabinol/pharmacology , Glycine/administration & dosage , Humans , TransfectionABSTRACT
Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. Cannabidiol is a nonpsychotropic plant constituent of Cannabis sativa. As we hypothesized that non-CB receptor mechanisms of cannabidiol might contribute to its anti-inflammatory and neuroprotective effects, we investigated the interaction of cannabidiol with strychnine-sensitive alpha(1 )and alpha(1)beta glycine receptors by using the whole-cell patch clamp technique. Cannabidiol showed a positive allosteric modulating effect in a low micromolar concentration range (EC(50) values: alpha(1) = 12.3 +/- 3.8 micromol/l and alpha(1)beta = 18.1 +/- 6.2 micromol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 micromol/l (EC(50) values: alpha(1) = 132.4 +/- 12.3 micromol/l and alpha(1)beta = 144.3 +/- 22.7 micromol/l). These in vitro results suggest that strychnine-sensitive glycine receptors may be a target for cannabidiol mediating some of its anti-inflammatory and neuroprotective properties.
Subject(s)
Cannabidiol/pharmacology , Cannabinoids/pharmacology , Receptors, Glycine/agonists , Cell Line, Transformed , Cells, Cultured , Embryonic Stem Cells , Glycine/pharmacology , Humans , In Vitro Techniques , Membrane Potentials/drug effects , Membrane Potentials/physiology , Receptors, Glycine/genetics , TransfectionABSTRACT
The synthetic cannabinoid ajulemic acid (CT-3) is a potent cannabinoid receptor agonist which was found to reduce pain scores in neuropathic pain patients in the absence of cannabis-like psychotropic adverse effects. The reduced psychotropic activity of ajulemic acid has been attributed to a greater contribution of peripheral CB receptors to its mechanism of action as well as to non-CB receptor mechanisms. Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. As we hypothesised that additional non-CB receptor mechanisms of ajulemic acid might contribute to its effect in neuropathic pain, we investigated the interaction of ajulemic acid with strychnine-sensitive alpha(1)- and alpha(1)beta-glycine receptors by using the whole-cell patch clamp technique. Ajulemic acid showed a positive allosteric modulating effect in a concentration range which can be considered close to clinically relevant concentrations (EC(50) values: alpha(1) = 9.7 +/- 2.6 microM and alpha(1)beta = 12.4 +/- 3.4 microM). Direct activation of glycine receptors was observed at higher concentrations above 100 microM (EC(50) values: alpha(1) = 140.9 +/- 21.5 microM and alpha(1)beta = 154.3 +/- 32.1 microM). These in vitro results demonstrate that ajulemic acid modulates strychnine-sensitive glycine receptors in clinically relevant concentrations.
Subject(s)
Dronabinol/analogs & derivatives , Receptors, Glycine/drug effects , Cell Line , Dronabinol/pharmacology , Electrophysiological Phenomena/drug effects , Glycine/pharmacology , Humans , Patch-Clamp Techniques , Protein Conformation/drug effects , Receptors, Glycine/agonists , Receptors, Glycine/genetics , Receptors, Neurotransmitter/agonists , Receptors, Neurotransmitter/drug effects , Receptors, Neurotransmitter/genetics , TransfectionABSTRACT
Inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the processing of nociceptive signals, and mainly involves glycine. We have studied the effects of alphaxalone on alpha(1) homomeric glycine receptors expressed in a mammalian expression system (HEK 293 cells) using the whole-cell patch-clamp technique. Our experiments showed a coactivating effect of alphaxalone with a concentration for half-maximum activation (EC(50)) of the effect of a low glycine concentration (EC(20)) of 70.9 +/- 21.5 micromol/l. Taking into account the results of other groups, our study suggests that neuroactive steroids might be an interesting class of compounds to probe subunit-specific effects of glycine receptors.
