EMDT oxalate

Calcium oxalate crystal related kidney injury in a patient receiving Roux-en Y hepaticojejunostomy due to gall bladder cancer.[Pubmed:28356078]

BMC Nephrol. 2017 Mar 29;18(1):106.

BACKGROUND: Calcium oxalate nephropathy is rare in current practice. It was a common complication during jejunoileal bypass, but much less seen in modern gastric bypass surgery for morbid obesity. The major cause of it is enteric hyperoxaluria. CASE PRESENTATION: We report on a patient here with acute kidney disease due to calcium oxalate nephropathy, rather than the conditions mentioned above. The male patient received a Roux-en Y hepaticojejunostomy and common bile duct drainage. In addition to enteric hyperoxaluria, chronic kidney disease related metabolic acidosis, chronic diarrhea related volume depletion, a high oxalate and low potassium diet, long term ascorbic acid intake and long term exposure to antibiotics, all predisposed him to having oxalate nephropathy. CONCLUSION: This is the first case with such conditions and we recommend that similarly diagnosed patients avoid all these predisposing factors, in order to avoid this rare disease and its undesired outcome.

Hydrolysis of nicosulfuron under acidic environment caused by oxalate secretion of a novel Penicillium oxalicum strain YC-WM1.[Pubmed:28381881]

Sci Rep. 2017 Apr 5;7(1):647.

A novel Penicillium oxalicum strain YC-WM1, isolated from activated sludge, was found to be capable of completely degrading 100 mg/L of nicosulfuron within six days when incubated in GSM at 33 degrees C. Nicosulfuron degradation rates were affected by GSM initial pH, nicosulfuron initial concentration, glucose initial concentration, and carbon source. After inoculation, the medium pH was decreased from 7.0 to 4.5 within one day and remained at around 3.5 during the next few days, in which nicosulfuron degraded quickly. Besides, 100 mg/L of nicosulfuron were completely degraded in GSM medium at pH of 3.5 without incubation after 4 days. So, nicosulfuron degradation by YC-WM1 may be acidolysis. Based on HPLC analysis, GSM medium acidification was due to oxalate accumulation instead of lactic acid and oxalate, which was influenced by different carbon sources and had no relationship to nicosulfuron initial concentration. Furthermore, nicosulfuron broke into aminopyrimidine and pyridylsulfonamide as final products and could not be used as nitrogen source and mycelium didn't increase in GSM medium. Metabolomics results further showed that nicosulfuron degradation was not detected in intracellular. Therefore, oxalate secretion in GSM medium by strain YC-WM1 led to nicosulfuron acidolysis.

[Expression of matrix Gla protein and bone morphogenetic protein 2 in renal papillary tissues in patients with calcium oxalate kidney stones].[Pubmed:28364100]

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2017 Mar 28;42(3):277-283.

OBJECTIVE: To compare expression levels of matrix Gla protein (MGP) and bone morphogenetic protein 2 (BMP-2) in Randall's plaque of renal papillary tissues in patients with calcium oxalate kidney stones and the underlying mechanism for stone formation. Methods: A total of 30 samples of Randall's plaque in renal papillary tissues from patients with calcium oxalate kidney stones were collected from the Department of Urology of Xiangya Hospital of Central South University from April, 2015 to December, 2015 and served as an experimental group. Ten samples of renal papillary tissues in patients undergone renal tumor nephrectomy were collected from the same hospital and served as a control group. The expressions of MGP and BMP-2 mRNA and protein were detected by quantitative real-time PCR and Western blot.Meanwhile, immunohistochemical technique was used to observe the expressions of MGP and BMP-2 in different parts of renal papillary tissues in the 2 groups. Results: 1) The mRNA expression levels of MGP in the experimental group and the control group were 0.760+/-0.804 and 1.365+/-0.348, respectively, with significant difference between them (P<0.05). Them RNA levels of BMP-2 in the experimental group and the control group were 2.500+/-0.725 and 1.485+/-0.870, respectively, with significant difference between them (P<0.05). The expression levels of MGP protein in the experimental group and the control group were 0.130+/-0.424 and 0.202+/-0.704, respectively, with no significant difference between them (P>0.05). The expression levels of BMP-2 protein in the experimental group and the control group were 0.885+/-0.220 and 0.682+/-0.272, respectively, with significant difference between them (P<0.05). The immunohistochemistry showed that the protein expression of MGP in the experimental group was lower than that in the control group, while the protein expression of BMP-2 in the experimental group was higher than that in the control group (both P<0.05). Conclusion: The BMP-2 expression is increased while MGP expression is decreased in renal papillary tissues in patients with calcium oxalate kidney stones, and the formation of calcium oxalate kidney stone might be a kind of osteogenetic reaction or ectopic calcification.

Pathogenesis of calcium oxalate urinary stone disease: species comparison of humans, dogs, and cats.[Pubmed:28361470]

Urolithiasis. 2017 Aug;45(4):329-336.

Idiopathic calcium oxalate nephrolithiasis is a highly recurrent disease that is increasing in prevalence. Decades of research have not identified effective methods to consistently prevent the formation of nephroliths or induce medical dissolution. Idiopathic calcium oxalate nephroliths form in association with renal papillary subepithelial calcium phosphate deposits called Randall's plaques (RPs). Rodent models are commonly used to experimentally induce calcium oxalate crystal and stone formation, but a rodent model that conclusively forms RPs has not been identified. Both dogs and cats form calcium oxalate uroliths that can be recurrent, but the etiopathologic mechanisms of stone formation, especially renal pathologic findings, are a relatively unexploited area of study. A large animal model that shares a similar environment to humans, along with a shorter lifespan and thus shorter time to recurrence, might provide an excellent means to study preventative and therapeutic measures, along with enhancing the concepts of the one health initiative. This review article summarizes and compares important known features of idiopathic calcium oxalate stone disease in humans, dogs, and cats, and emphasizes important knowledge gaps and areas for future study in the quest to discover a naturally occurring animal model of idiopathic calcium oxalate stone disease.

Biochemical and behavioral evidence for antidepressant-like effects of 5-HT6 receptor stimulation.[Pubmed:17428998]

J Neurosci. 2007 Apr 11;27(15):4201-9.

The primary action of several antidepressant treatments used in the clinic raises extracellular concentrations of serotonin (5-HT), which subsequently act on multiple 5-HT receptors. The present study examined whether 5-HT6 receptors might be involved in the antidepressant-like effects mediated by enhanced neurotransmission at 5-HT synapses. A selective 5-HT6 receptor antagonist, SB271046, was evaluated for its ability to counteract fluoxetine-induced biochemical and behavioral responses in mice. In addition, biochemical and behavioral effects of the 5-HT6 receptor agonist, 2-ethyl-5-methoxy-N,N-dimethyltryptamine (EMDT), were assessed in mice to ascertain whether enhancement of 5-HT6 receptor-mediated neurotransmission engenders antidepressant-like effects. SB271046 significantly counteracted the stimulatory actions of fluoxetine on cortical c-fos mRNA, phospho-Ser845-GluR1, and in the tail suspension antidepressant assay, whereas it had no effect on these parameters by itself. EMDT increased the phosphorylation states of Thr34-DARPP-32 and Ser845-GluR1, both in brain slices and in the intact brain, which were effects also seen with the antidepressant fluoxetine; as with fluoxetine, these effects were demonstrated to be independent of D1 receptor stimulation. Systemic administration of EMDT increased c-fos mRNA expression in the striatum and cerebral cortex and reduced immobility in the tail suspension test. The antidepressant-like effects of EMDT in the tail suspension test were prevented by SB271046. Our results indicate that 5-HT6 receptor stimulation may be a mechanism initiating some of the biochemical and behavioral outcomes of 5-HT reuptake inhibitors, such as fluoxetine. These findings also indicate that selective 5-HT6 receptor agonists may represent a novel antidepressant drug class.

2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors.[Pubmed:10715164]

J Med Chem. 2000 Mar 9;43(5):1011-8.

Several 2-alkyl-5-methoxytryptamine analogues were designed and prepared as potential 5-HT(6) serotonin agonists. It was found that 5-HT(6) receptors accommodate small alkyl substituents at the indole 2-position and that the resulting compounds can bind with affinities comparable to that of serotonin. In particular, 2-ethyl-5-methoxy-N, N-dimethyltryptamine (8) binds with high affinity at human 5-HT(6) receptors (K(i) = 16 nM) relative to 5-HT (K(i) = 75 nM) and was a full agonist, at least as potent (8: K(act) = 3.6 nM) as serotonin (K(act) = 5.0 nM), in activating adenylate cyclase. Compound 8 displays modest affinity for several other populations of 5-HT receptors, notably h5-HT(1A) (K(i) = 170 nM), h5-HT(1D) (K(i) = 290 nM), and h5-HT(7) (K(i) = 300 nM) receptors, but is otherwise quite selective. Compound 8 represents the first and most selective 5-HT(6) agonist reported to date. Replacing the 2-ethyl substituent with a phenyl group results in a compound that retains 5-HT(6) receptor affinity (i.e., 10: K(i) = 20 nM) but lacks agonist character. 2-Substituted tryptamines, then, might allow entry to a novel class of 5-HT(6) agonists and antagonists.