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[The effect of lithium derivatives of GABA on blood circulation and metabolic indices in the brain under ischemia].

In acute experiments on anesthetized cats with cerebral ischemia in conditions of autohemoperfusion of cerebral and peripheral vessels with a stable volume of blood we found that lithium oxybutirate and new GABA derivatives: LOS 1-84 and LOS 5-79 affect the cerebral blood flow and metabolism in the brain. Prophylactic intravenous injection of lithium oxybutirate did not affect the development of postischemic hyperperfusion but inhibited postischemic hyperperfusion. The compounds prevent the development of postischemic phenomena and promote the recovery of metabolism in the brain.

Animals↗
PubMed2003

Protective roles of mitochondrial manganese-containing superoxide dismutase against various stresses in Candida albicans.

Candida albicans contains copper- and zinc-containing superoxide dismutase but also two manganese-containing superoxide dismutases (MnSODs), one in the cytosol and the other in the mitochondria. Among these, the SOD2 gene encoding mitochondrial MnSOD was disrupted and overexpressed to investigate its roles in C. albicans. The null mutant lacking mitochondrial MnSOD was more sensitive than wild-type cells to various stresses, such as redox-cycling agents, heating, ethanol, high concentration of sodium or potassium and 99.9% O2. Interestingly, the sod2/sod2 mutant was rather more resistant to lithium and diamide than the wild-type, whereas overexpression of SOD2 increased susceptibility of C. albicans to these compounds. The inverse effect of mitochondrial MnSOD on lithium toxicity was relieved when the sod2/sod2 and SOD2-overexpressing cells were grown on the synthetic dextrose medium containing sulphur compounds such as methionine, cysteine, glutathione or sulphite, indicating that mitochondrial MnSOD may affect lithium toxicity through sulphur metabolism. Moreover, disruption or overexpression of SOD2 increased or decreased glutathione reductase activity and cyanide-resistant respiration by alternative oxidase, respectively. Taken together, these findings suggest that mitochondrial MnSOD is important for stress responses, lithium toxicity and cyanide-resistant respiration of C. albicans.

Candida albicans↗
PubMed2005

Synthesis, characterization, thermolysis and performance evaluation studies on alkali metal salts of TABA and NTO.

The lithium (Li) and potassium (K) salts of 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4,6-trinitroanilino benzoic acid (TABA) were prepared and characterized during this work. The synthesis was carried out by addition of a solution of lithium/potassium hydroxide to the aqueous solution of NTO and TABA, respectively. The products were characterized by elemental analysis, metal content determination and Fourier Transform Infrared (FTIR) Spectrum. Differential scanning calorimetry (DSC) profile indicated that Li and K salts of NTO and TABA undergo exothermic decomposition in the temperature range of 257-360 degrees C suggesting their energetic nature. The thermo gravimetric (TG) weight loss pattern revealed loss of water for Li/K salts of NTO and TABA in the temperature range of 115-155 degrees C. Sensitivity results revealed that the compounds are insensitive to impact and friction (impact sensitivity--height of 50% explosion>170 cm and friction insensitivity up to 36 kg) stimuli despite even the parent molecule of NTO salts (NTO) being HEM in the hazard category of 1.1. The FTIR spectra of the gaseous products evolved during TGA of NTO and TABA salts indicated the release of NO2. The formation of products such as LiNCO and KNCO was also observed in case of NTO salts, whereas that of CO2 and NH containing products was indicated in case of TABA salts during this study. In order to assess the performance as energetic ballistic modifiers (EBMs), NTO and TABA salts were incorporated in the ammonium perchlorate-hydroxyl terminated polybutadiene (AP-HTPB) composite propellants. The potassium salts enhanced the burning rate of the propellant. The best catalytic effect was obtained with K-TABA salt, which increased the burning rate to the extent of approximately 81% as well as brought down the n-value to 0.15 (pressure 2-9 MPa).

Aniline Compounds↗
PubMed1992

Lithium effects on inositol phospholipids and inositol phosphates: evaluation of an in vivo model for assessing polyphosphoinositide turnover in brain.

Administration of lithium chloride to rats injected intracerebrally with [3H]inositol led to time- and dose-dependent increases in levels of labeled inositol monophosphates in brain. Quantitative analysis of the inositol phosphates by ion chromatography revealed 37- and 20-fold increases in the mass of myo-inositol 1-phosphate and 4-phosphate, respectively, at 4 h intraperitoneal after injections of 6 mEq/kg of lithium chloride. Albeit to a much lesser extent, lithium administration also resulted in an increase in the level of myo-inositol, 1,4-bisphosphate in brain. The lithium-induced increase in content of labeled inositol monophosphates was marked by a concomitant decrease in content of labeled inositol, and after injections of high doses of lithium, e.g., 10 mEq/kg, this was followed by a general decrease in labeling of the inositol phospholipids. In general, animals injected with [3H]inositol but not lithium did not reveal obvious differences in labeling of inositol monophosphates on stimulation by mecamylamine or pilocarpine. However, when animals were injected with [3H]inositol and then lithium, there were large increases in the levels of labeled inositol monophosphates on administration of these compounds. Administration of atropine to the lithium-treated mice led to a partial reduction in the amount of labeled inositol monophosphates accumulated due to the administration of lithium alone. Furthermore, atropine was able to block the pilocarpine-induced increase in level of labeled inositol monophosphates. These results demonstrate the suitable use of the radiotracer technique together with lithium administration for assessing the effects of drugs and receptor agonists on the signaling system involving polyphosphoinositide turnover in brain.

Animals↗
PubMed1999

Preparation and Synthetic Applications of Enantiopure (2S,3S)- or (2R,3S)-2-Halomethyl-1,2-epoxyalkan-3-amines.

Enantiomerically pure (2S,3S)-3 and its diastereoisomer (2R,3S)-2-halomethyl-1,2-epoxyalkan-3-amine 4 have been obtained from 1-aminoalkyl halomethyl ketones 1 and (iodomethyl)lithium or (chloromethyl)lithium, respectively. Some synthetic applications of compounds 3 are described: chiral unsaturated 1,3-aminoalcohols 8 or 2-(halomethylidene)-3-(dibenzylamino)-alkan-1-ol 11 is obtained from 3 by halogeno-lithium or by hydrogen-lithium exchange, respectively. Transformation of 8c into its methyl ester derivative 9c is also reported.

Journal Article↗
PubMed1987

Metal toxicity in the central nervous system.

The nervous system is the principal target for a number of metals. Inorganic compounds of aluminum, arsenic, lead, lithium, manganese, mercury, and thallium are well known for their neurological and behavioral effects in humans. The alkyl derivatives of certain metals--lead, mercury and tin--are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein sythesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages. These and other hypotheses will stimulate considerable experimental challenges in the future.

Animals↗
PubMed1983

Chemical aspects of propranolol metabolism: 1,1-diethoxy-3-(1-naphthoxy)-2-propanol and related ring-closure products cis- and trans-4-ethoxy-3-hydroxy-3,4-dihydro-2H-naphtho[1,2-b]pyran.

1,1-Diethoxy-3-(1-naphthoxy)-2-propanol (V), the diethyl acetal of an important aldehyde intermediate in the metabolic N-deal-kylation of propranolol, was prepared from compound X, the product of the reaction of the lithium salt of methyl methylsulfinylmethyl sulfide with 2-(1-naphthoxy)-acetaldehyde. Compound X, as a mixture of three diastereomeric alpha-hydroxydithioacetal derivatives, when treated with ethyl orthoformate afforded the desired acetal V as well as two ring-closure products, the dihydronaphtho[1,2-b]pyrans VI and VII. Compounds VI and VII were characterized on the basis of mass spectral and 1H- and 13C-NMR data. The stereochemistry of these compounds was assigned on the basis of the 300-MHz 1H-NMR spectra of their acetate esters (XI and XII).

Biotransformation↗
PubMed2002

Electronically conductive phospho-olivines as lithium storage electrodes.

Lithium transition metal phosphates have become of great interest as storage cathodes for rechargeable lithium batteries because of their high energy density, low raw materials cost, environmental friendliness and safety. Their key limitation has been extremely low electronic conductivity, until now believed to be intrinsic to this family of compounds. Here we show that controlled cation non-stoichiometry combined with solid-solution doping by metals supervalent to Li+ increases the electronic conductivity of LiFePO4 by a factor of approximately 10(8). The resulting materials show near-theoretical energy density at low charge/discharge rates, and retain significant capacity with little polarization at rates as high as 6,000 mA x g(-1). In a conventional cell design, they may allow development of lithium batteries with the highest power density yet.

Electric Capacitance↗
PubMed2006

Suicide attempts amongst elderly bipolar patients.

BACKGROUND: Bipolar disorder is associated with high risk of suicide. In the elderly suicide rates are the highest of all age groups. There is a paucity of data regarding suicide amongst elderly bipolar patients. Mood stabilizers and particularly lithium are established as "antisuicide" compounds. OBJECTIVE: We aimed to evaluate the association between exposure to psychotropic drugs and suicide attempts in a cohort of elderly patients suffering from bipolar affective disorder (BAD). METHOD: This was a preliminary, retrospective, matched, case-controlled evaluation over a 10-year period. All records of admissions of patients with BAD (ICD-10) were assessed. The index group comprised all patients who had attempted suicide in the month prior to admission. The control group consisted of the next admission of a patient suffering from BAD, matched for sex and age who had not attempted suicide in the month prior to admission. RESULTS: The index group during the period 1995 to 2004 consisted of 16 patients, (8 men and 8 women.), mean age 74.8 +/- 1.3 years. The control group patients (N = 16) were matched for age (mean 74.3 +/- 1.5 years) and sex. The number of patients who had a history of a suicide attempt was significantly greater in the index group (7/16 vs., 2/16; p = 0.039). In the control group patients treated by both a mood stabilizer and an antidepressant were at a significantly lower risk for recent suicide attempt (p = 0.047). LIMITATIONS: Sample size is small, treatments were not standardized and data were collected retrospectively. CONCLUSION: Elderly BAD patients treated with mood stabilizers and antidepressants may be at reduced risk of attempting suicide. These findings need support from prospective randomized trials.

Aged↗
PubMed2001

Gallane complexes with amido-amine ligands.

Gallane complexes bearing amido-amine ligands -N(R)CH2CMe2CH2NMe2 [R = H or SiMe3 (TMS)], (H2Ga[N(H)CH2CMe2CH2NMe2])2, 1, H2Ga[N(TMS)CH2CMe2CH2NMe2], 2, (H(Cl)Ga[N(H)CH2CMe2CH2NMe2])2, 3, ([(TMS)2N](H)Ga[N(H)CH2CMe2CH2NMe2])2, 4, and HGa[N(TMS)CH2CMe2CH2NMe2]2, 5, were synthesized from the reactions of the quinuclidine adducts of mono- and dichlorogallane with the corresponding lithium amides. Structural determinations of compounds 1, 3, and 4 showed all were dimeric with bridging amido groups. Rather than bond to gallium the tertiary amine groups in 1 and 4 were hydrogen-bonded to the amino N-H. In the structure of compound 3 the amine group occupied an axial position in the trigonal bipyramidal geometry of the five-coordinate gallium. The results were rationalized in terms of the steric and electronic properties of gallium ligands.

Journal Article↗
PubMed1998

Laboratory support for the poisoned patient.

Poisoning often does not require toxicology laboratory analysis, though support is necessary from the departments of hematology and biochemistry. There are some compounds, such as paracetamol (acetaminophen), lithium, and methanol, for which quantitative or qualitative analysis is essential for effective patient management. Standard methods such as immunoassays, chromatography, and spectrophotometry have been extended by mass spectrometry and will be enhanced by nuclear magnetic resonance and by hyphenated techniques (e.g., LC-MS-MS). The new perspectives that can be gained with these techniques may greatly improve our knowledge of toxicokinetics and enable better patient management. Comatose patients and those with suspected brain death comprise a difficult group requiring comprehensive toxicologic screens. Although current immunoassay-chromatography methods are adequate, it is to be hoped that more comprehensive screens are achievable. The author has performed trials on TLC-FABMS-MS as a potential procedure and has obtained satisfactory preliminary results. This and other spectrometric-spectroscopic methods may be the techniques of the future for reference centers.

Clinical Laboratory Techniques↗
PubMed2000

[The use of enterosorbents for preventing and stopping chronic toxic stress in submariners].

The efficiency of prophylactic intestinal sorbents use (algisorb and activated carbon) to prevent chronic toxic stress was investigated in 20 healthy volunteers (atomic submarine personnel) basing on evaluation of central nervous system functional state, hemodynamics, hepatic detoxicative ability and dynamics of trace elements in urine. It was revealed that intestinal sorbents administration in daily dose of 5 g during 20 days promotes gastrointestinal elimination of toxic compounds (cadmium, bismuth, chrome, molybdenum, lithium). It is accompanied with decrease in organism intoxication evidences: reduction in central nervous system excessive excitation, decrease in functional tension of cardiovascular system, recovery of hepatic detoxicative ability. Algisorb has an advantage over activated carbon that allows to recommend this drug in prophylaxis and arresting of chronic toxic stress in submariners both during interfield period and autonomic sailing.

Adolescent↗
PubMed1993

Pharmacological approach of the treatment of drinking problems: a critical overview.

Many pharmacological agents have been proposed for the treatment of drinking problems. However, there are many pitfalls in the assessment of the clinical interest of those drugs. In this paper, we propose a new classification of drugs of interest for treating alcohol abuse and related problems. We also review the major clinical studies about those pharmacological agents and discuss, through the studies about serotonergic agents, lithium salts, disulfiram and related compounds, some peculiar aspects of those trials that we think to be important to develop better strategies for the evaluation of pharmacotherapy of alcoholism.

Alcohol Deterrents↗
PubMed1998

Modification of the reductive pathway in gamma-irradiated DNA by electron scavengers: targeting the sugar-phosphate backbone.

Several electron scavengers that irreversibly form potential hydrogen-abstracting species upon one-electron reduction have been tested as agents for conversion of reductive damage to DNA bases into damage to the sugar-phosphate backbone. Electron spin resonance spectroscopy is employed to follow the production of radicals and transformations after irradiation. The scavengers tested included neutral (acrylamide, iodoacetamide) and cationic [triphenylsulfonium (Ph3S+), o,o'-diphenylenebromonium (DPB) and o,o'-diphenyleneiodonium (DPI)] compounds. Modification of reductive radiation damage in DNA is found to occur by scavenging of initial mobile electrons at low temperatures as well as thermally activated electron transfer from DNA electron-gain centers upon annealing. Electron transfer from the bases to hydrogen-bonded acrylamide has the smallest activation energy among other scavengers but produces a secondary alkyl radical incapable of abstracting hydrogen from the sugar-phosphate backbone. A primary alkyl radical generated from iodoacetamide has been shown to abstract preferentially from the thymine methyl group but not from deoxyribose moieties. Aryl radicals generated from aromatic onium salts such as Ph3S+, and especially DPI and DPB, are found to be the agents which best abstract hydrogen atoms from the deoxyribose portion of DNA. The use of DPB and DPI as radiation modifiers allows the elimination of undesirable side reactions of aryl radicals and through hydrogen abstraction results in high yields of a species identified as the DNA C1'. sugar radical. The second reaction pathway found for DPI and DPB in DNA is addition of an aryl radical to the thymine 5,6 double bond. Cysteamine is shown to preferentially eliminate sugar radicals upon annealing and to have little impact on the thermal stability of the thymine adduct radical.

Acrylamide↗