Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.
- MeSH
- Ammonia metabolism MeSH
- Arginine therapeutic use MeSH
- Citrulline MeSH
- Hyperammonemia * drug therapy MeSH
- Carbamyl Phosphate metabolism therapeutic use MeSH
- Carbamoyl-Phosphate Synthase (Ammonia) metabolism MeSH
- Humans MeSH
- Ornithine Carbamoyltransferase Deficiency Disease * surgery MeSH
- Ornithine Carbamoyltransferase MeSH
- Retrospective Studies MeSH
- Liver Transplantation * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
The use of knowledge from technetium radiochemistry (even from nuclear medicine applications) allows us to select an sorbent for 99mTc radionuclide sorption, which is hydroxyapatite. Using radioisotope indication, the 99mTcO4- sorption process on synthetic hydroxyapatite was studied by the batch method in the presence of SnCl2 and FeSO4 reducing agents. The complexing organic ligands' effect on the 99mTcO4- sorption under reducing conditions was investigated. In the presence of Sn2+ ions without the addition of organic ligand, the sorption percentage reached above 90% independently of the environment. In the presence of Fe2+ ions without the addition of organic ligand, the sorption of 99mTcO4- was significantly lower and was at approximately 6%, depending on the concentration of Fe2+ ions in solution. The effect of complexing organic ligands on the 99mTcO4- sorption on hydroxyapatite from the aqueous solution, acetate buffer and phosphate buffer decreases in the following order for Sn2+: oxalic acid > ethylenediaminetetraacetic acid > ascorbic acid. In the presence of Fe2+ ions without organic ligands, the sorption reached up to 15% depending on the composition of the solution. The addition of oxalic acid and ascorbic acid increased the sorption up to 80%. The ethylenediaminetetraacetic acid had no significant effect on the sorption of technetium on hydroxyapatite.
The aim of this study was to improve rivaroxaban water-solubility by cocrystal preparation and to understand this process. The screening with water-soluble coformers was performed via both mechanochemical and solution-mediated techniques. Two cocrystals of rivaroxaban with malonic acid and oxalic acid were prepared, and the structure of the cocrystal with oxalic acid was solved. Both cocrystals exhibit improved dissolution properties. The mechanism of the supersaturation maintenance was studied by in-situ Raman spectroscopy. The transformation into rivaroxaban dihydrate was identified as the critical step in the improved dissolution properties of both cocrystals. Moreover, the transformation kinetics and solubilization effects of the coformers were identified as responsible for the differences in the dissolution behavior of the cocrystals. In-vivo experiments proved that the use of cocrystal instead of form I of free API helped to increase the bioavailability ofrivaroxaban.
- MeSH
- X-Ray Diffraction MeSH
- Crystallization MeSH
- Oxalic Acid MeSH
- Rivaroxaban * MeSH
- Solubility MeSH
- Water * chemistry MeSH
- Publication type
- Journal Article MeSH
We compared the efficiency of real-time PCR analysis of FII (c.*97G>A, G20210A) and FV Leiden (c.1601G>A) thrombophilic mutations in the samples obtained from venous blood treated with various anti coagulant agents (EDTA, heparin, and sodium fluoride with potassium oxalate), or from clotted venous blood; one hundred samples of wild-type subjects were tested. Genomic DNA extracts and whole blood specimens modified by 90 °C heating were analysed by real-time PCR analysis; cycle threshold values were subsequently evaluated. Real-time PCR analysis for the FII gene assay performed in DNA extracts from EDTA blood samples revealed a median Ct value of 19.3. Similar Ct values were apparent in the DNA extracts obtained from the heparinized blood and sodium fluoride with potassium oxalatetreated samples: 18.5 and 18.9, respectively. Significantly higher Ct values were found in extracts from clotted blood with medians of 20.6 (tubes with inert separation gel) and 20.5 (tubes without the gel, both P < 0.001). The data on the FV real-time PCR analysis were very comparable to the FII assay. In the modified whole blood, the samples treated with heparin salts showed significantly lower Ct values (P < 0.001) in both assays when compared with the samples with EDTA, sodium fluoride with potassium oxalate, and with the samples with clotted blood. Our results indicate that real-time PCR analyses of thrombophilic mutations were not negatively influenced by the presence of heparin salts in collection tubes. Blood samples with various anticoagulants might be exchangeable for each other when DNA analysis of thrombophilic mutations is required.
- MeSH
- DNA MeSH
- Edetic Acid pharmacology MeSH
- Sodium Fluoride MeSH
- Heparin pharmacology MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Oxalic Acid MeSH
- Humans MeSH
- Mutation genetics MeSH
- Salts * MeSH
- Thrombophilia * genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Lithium (Li) represents a first choice mood stabilizer for bipolar disorder (BD). Despite extensive clinical use, questions regarding its mechanism of action and pathological mechanism of renal function impairment by Li remain open. The present study aimed to improve our knowledge in this area paying special attention to the relationship between the length of Li action, lipid peroxidation (LP), and Na+/K+-ATPase properties. The effects of therapeutic Li doses, administered daily to male Wistar rats for 1 (acute), 7 (short term) and 28 days (chronic), were studied. For this purpose, Na+/K+-ATPase activity measurements, [3H]ouabain binding and immunoblot analysis of α-Na+/K+-ATPase were performed. Li-induced LP was evaluated by determining the malondialdehyde concentration by HPLC. Sleep deprivation (SD) was used as an experimental approach to model the manic phase of BD. Results obtained from the kidney were compared to those obtained from erythrocytes and different brain regions in the same tested animals. Whereas treatment with therapeutic Li concentration did not bring any LP damage nor significant changes of Na+/K+-ATPase expression and [3H]ouabain binding in the kidney, it conferred strong protection against this type of damage in the forebrain cortex. Importantly, the observed changes in erythrocytes indicated changes in forebrain cortices. Thus, different resistance to SD-induced changes of LP and Na+/K+-ATPase was detected in the kidney, erythrocytes and the brain of Li-treated rats. Our study revealed the tissue-specific protective properties of Li against LP and Na+/K+-ATPase regulation.
- MeSH
- Antimanic Agents administration & dosage pharmacology MeSH
- Bipolar Disorder drug therapy MeSH
- Time Factors MeSH
- Erythrocytes drug effects metabolism MeSH
- Rats MeSH
- Kidney drug effects metabolism MeSH
- Lithium Carbonate administration & dosage pharmacology MeSH
- Disease Models, Animal MeSH
- Brain drug effects metabolism MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Wistar MeSH
- Sodium-Potassium-Exchanging ATPase metabolism MeSH
- Sleep Deprivation psychology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Keywords
- sekundární nefrotický syndrom,
- MeSH
- Anti-Anxiety Agents administration & dosage therapeutic use MeSH
- Biomarkers blood urine MeSH
- Biopsy methods utilization MeSH
- Diuresis physiology drug effects MeSH
- Edema diagnosis etiology complications MeSH
- Drug Therapy MeSH
- Hyperkalemia diagnosis etiology therapy MeSH
- Humans MeSH
- Lithium Carbonate * administration & dosage adverse effects therapeutic use MeSH
- Adolescent MeSH
- Nephrology MeSH
- Nephrotic Syndrome diagnosis etiology MeSH
- Drug-Related Side Effects and Adverse Reactions etiology complications MeSH
- Proteinuria diagnosis etiology complications MeSH
- Anxiety Disorders * diagnosis drug therapy complications MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Lithium (Li) is a typical mood stabilizer and the first choice for treatment of bipolar disorder (BD). Despite an extensive clinical use of Li, its mechanisms of action remain widely different and debated. In this work, we studied the time-course of the therapeutic Li effects on ouabain-sensitive Na+/K+-ATPase in forebrain cortex and hippocampus of rats exposed to 3-day sleep deprivation (SD). We also monitored lipid peroxidation as malondialdehyde (MDA) production. In samples of plasma collected from all experimental groups of animals, Li concentrations were followed by ICP-MS. The acute (1 day), short-term (7 days) and chronic (28 days) treatment of rats with Li resulted in large decrease of Na+/K+-ATPase activity in both brain parts. At the same time, SD of control, Li-untreated rats increased Na+/K+-ATPase along with increased production of MDA. The SD-induced increase of Na+/K+-ATPase and MDA was attenuated in Li-treated rats. While SD results in a positive change of Na+/K+-ATPase, the inhibitory effect of Li treatment may be interpreted as a pharmacological mechanism causing a normalization of the stress-induced shift and return the Na+/K+-ATPase back to control level. We conclude that SD alone up-regulates Na+/K+-ATPase together with increased peroxidative damage of lipids. Chronic treatment of rats with Li before SD, protects the brain tissue against this type of damage and decreases Na+/K+-ATPase level back to control level.
- MeSH
- Antimanic Agents pharmacology therapeutic use MeSH
- Hippocampus drug effects metabolism MeSH
- Binding, Competitive drug effects MeSH
- Rats MeSH
- Lithium Carbonate pharmacology MeSH
- Malondialdehyde metabolism MeSH
- Ouabain metabolism MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Wistar MeSH
- Prosencephalon drug effects enzymology metabolism MeSH
- Sodium-Potassium-Exchanging ATPase metabolism MeSH
- Sleep Deprivation drug therapy enzymology metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Lithium is widely used in psychiatry to treat bipolar affective disorders since 1970 but little is known about the incidence, clinical course and associated factors of acute lithium intoxication. Moderate and severe cases of lithium intoxication are rare. This case reports a patient with acute lithium intoxication (serum level of 3.7 mmol/L) with neurological symptoms imitating stroke, which affects the differential diagnosis in the pre-hospital and hospital care. Patient was treated with forced diuresis and dismissed 21 days after admission.
- MeSH
- Antimanic Agents adverse effects therapeutic use MeSH
- Bipolar Disorder drug therapy MeSH
- Stroke diagnosis MeSH
- Diagnosis, Differential MeSH
- Humans MeSH
- Lithium blood MeSH
- Lithium Carbonate adverse effects therapeutic use MeSH
- Drug Overdose blood diagnosis MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
BACKGROUND: Lithium in the form of lithium carbonate (Li2CO3) has become one of the most effective and widely prescribed drugs for mood stabilization. However, lithium has adverse effects on renal tubular functions, such as decreased concentrating function of the kidneys, and even occasional symptoms of nephrogenous diabetes insipidus occur with additional evidence of glomerular disruption in lithium-treated patients. METHODS: We assessed the kidney function of patients with bipolar disorder who are under long-term lithium treatment using novel markers of kidney damage such as plasma neutrophil gelatinase-associated lipocalin, cystatin C, albuminuria, estimated glomerular filtration rate, Chronic Kidney Disease-Epidemiology Investigation using creatinine and cystatin C, and serum and urinary osmolality, and compared the results with those of age-matched patients with bipolar disorder not treated with lithium. The study enrolled 120 patients with bipolar disorder, consisting of 80 (30 male and 50 female patients) who have been receiving lithium for 0.5 to 20 (mean, 7) years and 40 (10 male and 30 female patients) who had never been exposed to lithium treatment. RESULTS: Patients treated with lithium had significantly decreased urine osmolality (mean ± SD, 405 ± 164 vs 667 ± 174 mmol/kg) and urine-to-serum osmolality ratio (1.35 ± 0.61 vs 2.25 ± 0.96). No significant difference was found in creatinine, estimated glomerular filtration rate values calculated using the Chronic Kidney Disease-Epidemiology Investigation using creatinine and cystatin C, neutrophil gelatinase-associated lipocalin, cystatin C, and albuminuria between both groups. We found no significant difference in renal biomarkers between patients treated with lithium for 6 to 24 months and those treated for 25 to 240 months. CONCLUSIONS: We found significantly decreased kidney concentrating ability in the long-term lithium-treated patients compared with the control group. Other renal function markers did not indicate any significant signs of renal dysfunction.
- MeSH
- Antimanic Agents administration & dosage adverse effects MeSH
- Biomarkers metabolism MeSH
- Bipolar Disorder drug therapy MeSH
- Time Factors MeSH
- Adult MeSH
- Glomerular Filtration Rate MeSH
- Middle Aged MeSH
- Humans MeSH
- Lithium Carbonate administration & dosage adverse effects MeSH
- Kidney Diseases chemically induced epidemiology MeSH
- Aged MeSH
- Kidney Function Tests MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
