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At least 19 recordsLinked to original sources
PubMed1979

Lithium compound treatment and psoriasis.

Observations were made of 12 cases of psoriasis that developed and three cases of psoriasis that became exacerbated during treatment with lithium compounds. Only two patients had a family history of psoriasis, and results of a search for increased frequencies of the histocompatibility antigens seen in psoriasis vulgaris were negative. The clinical features were identical to severe psoriasis vulgaris and the diagnosis was confirmed by histologic examination performed in six cases. However, the skin changes disappeared or returned to pretreatment level after withdrawal of lithium compounds. A positive provocation test result was obtained in two cases, the secondary latency time being shorter than the primary. We suggest that the psoriasis was induced or exacerbated by lithium compounds.

Adult↗
PubMed1977

[Some peculiarities of lithium intoxication in the elderly].

This is a report on two 73- and 68-year-old female patients with monophasic mania, who had been treated with lithium compounds for six years (without showing any complications) and who, because of a relapse of mania, were therapeutically treated with lithium compounds on an inpatient basis. The intoxications observed in the two female patients are described. Also discussed are the peculiarities of lithium intoxication in old age.

Aged↗
PubMed1992

Effects of lithium and purinergic compounds on the behavioral and physiological aspects of restraint stress in rats.

This study investigates the effects of lithium and caffeine on psychomotor activities, defecation, and gastric lesions induced by restraint stress. Rats exposed to restraint stress typically exhibited a biphasic response consisting of an initial hypermotility (such as tail-flipping, body-rolling, jaw movement, and vocalization) accompanied by defecation, and followed by hypomotility (decrease in motility) accompanied by gastric ulceration. Lithium chloride (150 micrograms, ICV; 50 and 100 mg/kg, IP) significantly attenuated these responses while N6-cyclohexyl adenosine (CHA; 1.5 micrograms, ICV; 0.3 mg/kg, IP), a potent adenosine A1 receptor agonist, attenuated the behavioral effects but potentiated the gastric ulceration. Caffeine (3 micrograms, ICV; 1.0 mg/kg, IP), an adenosine receptor antagonist, inhibited the effects of CHA in animals exposed to 3 h of stress, but aggravated the effects in animals exposed to 6-12 h of stress. These results suggest that caffeine consumption may produce supersensitivity of adenosine receptors, which potentiate the actions of adenosine or CHA. Lithium may modulate the effects of stress by indirectly inhibiting central adenosine receptor activity.

Adenosine↗
PubMed1992

alpha-Tocopherol oxidation mediated by superoxide anion (O2-). I. Reactions in aprotic and protic conditions.

The reaction of alpha-tocopherol (alpha-T) with superoxide anion (O2-) in both dry acetonitrile and in aqueous acetonitrile solution is described. The O2- was generated by the electrochemical reduction of molecular oxygen in acetonitrile, using tetrabutylammonium bromide as an electrolyte. alpha-T was reacted with O2- either in dry acetonitrile or in a 10% aqueous acetonitrile solution. In dry acetonitrile, alpha-T was oxidized to a very unstable primary intermediate, which was further oxidized to a secondary, more stable intermediate. The formation of the secondary intermediate depended upon the presence of molecular oxygen. This intermediate readily converted into two compounds in equimolar amounts (designated A and B). The primary, very unstable intermediate was readily reduced again to alpha-T by treatment with LiAlH4 or ascorbic acid. However, the secondary intermediate or the stable oxidation products could not be reduced to alpha-T. In the 10% aqueous acetonitrile, alpha-T was oxidized to alpha-tocopheryl quinone, alpha-tocopherol dimer and alpha-tocopherol dihydroxy dimer, and an unknown compound. In the aqueous medium, no intermediates were formed by the action of O2-. The results of this study indicate that the reaction of alpha-T with O2- under aprotic conditions is different from that observed under protic conditions.

Aluminum↗
PubMed1992

The human brain resonance of choline-containing compounds is similar in patients receiving lithium treatment and controls: an in vivo proton magnetic resonance spectroscopy study.

Lithium specifically and potentially inhibits membrane transport of choline. However, the effect of lithium on human neuronal choline content is unknown. This study was performed to determine if lithium alters the human brain choline concentration in vivo. In vivo proton magnetic resonance spectroscopy was used to compare the relative brain concentration of choline-containing compounds in seven lithium-treated patients and six lithium-free controls. No significant difference was observed in the mean relative choline resonance between the patient and control groups. Lithium treatment did not appear to alter the overall brain content of choline-containing compounds. It remains possible that a component of these compounds, particularly free choline, is elevated during lithium treatment.

Adult↗
PubMed1979

Synthesis, properties and reactions of 3 beta-benzoyloxy-7 alpha-15 beta-dichloro-5 alpha-cholest-8(14)-ene.

Treatment of 3 beta-benzoyloxy-14 alpha,15 alpha-epoxy-5 alpha-cholest-7-ene (I) with gaseous HCl in chloroform at -40 degrees C gave, in 87% yield, 3 beta-benzoyloxy-7 alpha,15 beta-dichloro-5 alpha cholest-8(14)-ene (III). Reduction of the latter compound with lithium aluminum hydride in ether at room temperature for 20 min gave, in 86% yield, 7 alpha-15 beta-dichloro-5 alpha-cholest-8(14)-en-3 beta-ol (IV). The latter compound was fully characterized and assignments of the individual carbon peaks in the 13C nuclear magnetic resonance spectra of this sterol have been completed. Reduction of III with excess lithium aluminum hydride in refluxing ether for 4 days gave, in 74% yield, 5 alpha-cholesta-7,14-dien-3 beta-ol (VI). Reduction of the dichloro-steryl benzoate III with lithium triethylborohydride in tetrahydrofuran gave, in 88% yield, 5 alpha-cholest-8(14)-en-3 beta-ol (VII). A similar reduction using lithium triethylborodeuteride led to the formation of [7 beta, 15 xi-2 H2]-VIIa. Treatment of III with concentrated HCl in a mixture of chloroform and methanol gave, in 79% yield, 3 beta-benzoyloxy-5 alpha-cholest-8(14)-en-15-one (II) which was characterized as such and as the corresponding free sterol.

L Cells↗
PubMed1992

Quinobene, a new potent anti-HIV agent.

A simple synthesis of the sulfonated azo dye Quinobene (3) and its derivatives, as well as the results of their evaluation in anti-HIV screening have been described. Thus, reacting the diazonium salt of 4,4'-diaminostilbene-2,2'-disulfonic acid with 8-hydroxyquinoline-5-sulfonic acid yielded the readily isolable title compound. The lithium and tetramethylammonium salts of Quinobene and its complexes with Cu(II), Zn(II), Mg(II) were also prepared. In vitro tests showed considerable activity of these compounds against HIV-1.

Antiviral Agents↗
PubMed1978

Synthesis of oximes, aziridines, and allyl alcohols derived from substituted 1-phenyl-1-nonen-3-ones as potential cytotoxic and antitumor agents.

A number of nuclear-substituted 1-phenyl-1-nonen-3-one oximes were synthesized. Reduction of several of these compounds with lithium aluminum hydride yielded the corresponding 1-phenyl-2,3-epiminononanes, shown by 100-MHz NMR spectroscopy to be the cis-geometrical isomers. When several ring-substituted 4-dimethylaminomethyl-1-phenyl-1-nonen-3-ones were treated with hydroxylamine hydrochloride under forcing conditions, the product isolated was the corresponding oxime. Reaction under mild conditions led only to the isolation of the Michael addition product of the oxime in low yield. Reduction of some nuclear-substituted 4-dimethylaminomethyl-1-phenyl-1-nonen-3-ones with sodium borohydride led to the formation of the corresponding allyl alcohols, and the products were shown by 1H- and 13C-NMR spectroscopy to be the threo-isomers or, alternatively, a mixture of erythro- and threo-isomers. Reaction of phosphoric acid with one of the substituted allyl alcohols led to a diolefin, shown by NMR spectroscopy to be a mixture of (E, E)- and (E, Z)-isomers in a ratio of 65:35.

Allyl Compounds↗
PubMed2025

Polygenic Contributions to Lithium Augmentation Outcomes in Unipolar Depression.

IMPORTANCE: Lithium augmentation is an effective treatment for patients with major depression after inadequate antidepressant response, but therapeutic outcomes vary considerably between individuals. Molecular studies may provide novel insights into treatment prediction and guide personalized therapy. OBJECTIVE: To investigate the association of polygenic risk scores (PRS) for schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) with clinical outcomes after lithium augmentation. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed prospectively assessed treatment outcomes in patients who underwent lithium augmentation. Disorder-specific PRS were calculated using well-powered genome-wide association study summary statistics. Participants were recruited from 13 psychiatric hospitals, primarily in the greater Berlin area, between 2008 and 2020. They were patients with MDD who showed inadequate response to at least 1 antidepressant, a baseline score of 12 or more on the 17-item Hamilton Depression Rating Scale (HAMD-17), adequate treatment duration (≥4 weeks), and no diagnostic or co-medication changes. Data analysis was conducted between June 2022 and November 2023. EXPOSURE: Polygenic risk scores for MDD, SCZ, or BIP. MAIN OUTCOMES AND MEASURES: Response was defined as a 50% or greater reduction in HAMD-17 score, remission as a HAMD-17 score of 7 or less. Cox proportional hazards models, adjusted for ancestry, demographic, and clinical covariates, were used to estimate hazard ratios (HRs) for favorable outcomes. RESULTS: Among 193 patients (mean [SD] age, 49.5 [13.4] years; 118 [61.1%] female and 75 [38.9%] male), higher BIP-PRS were associated with both response (HR, 1.29; 95% CI, 1.02-1.63; P = .03) and remission (HR, 1.52; 95% CI, 1.14-2.04; P = .004), explaining 2.51% and 4.53% of the variability in treatment outcomes, respectively. Individuals in the highest tertile of the BIP-PRS distribution had a 2.02-fold (95% CI, 1.15-3.53) higher likelihood of response and a 2.26-fold (95% CI, 1.17-4.36) higher chance of remission compared with those in the lowest tertile. Additionally, lower MDD-PRS was associated with better response to lithium augmentation (HR, 0.81; 95% CI, 0.66-1.00; P = .048; Nagelkerke R2 = 1.99%). No significant associations were observed between SCZ-PRS and response (HR, 1.00; 95% CI, 0.80-1.24; P = .97) or remission (HR, 1.12; 95% CI, 0.85-1.48; P = .42). CONCLUSIONS AND RELEVANCE: Individuals carrying a higher polygenic burden for BIP and lower polygenic risk for MDD are more likely to benefit from lithium augmentation. Our findings suggest that disease-related PRS may aid in developing treatment prediction models for lithium augmentation response in depression, potentially informing clinical decision-making.

Humans↗
PubMed1977

Sterol synthesis. Syntheses of 15-oxygenated 5alpha, 14beta-cholest-7-en-3beta-ol derivatives.

Treatment of 3beta-benzoyloxy-14alpha, 15alpha-epoxy-5alpha-cholest-7-ene with boron trifluoride-etherate gave, in 43% yield, 3alpha-benzoyloxy-5alpha, 14beta-cholest-7-en-15-one with the unnatural C-D ring juncture. Reduction of the latter compound with lithium aluminum hydride gave 15alpha, 14beta-cholest-7-en-3beta, 15alpha-diol and 5alpha, 14beta-cholest-7-en-3beta, 15beta-diol in 9% and 81% yields, respectively.

Cholestenes↗
PubMed2018

Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder.

Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.

Adult↗
PubMed2025

Genome-wide methylation biomarkers and biological aging in patients with bipolar disorder characterized for lithium response.

BACKGROUND: Epigenetic mechanisms might play a role in modulating susceptibility to bipolar disorder (BD) and response to lithium, the mainstay treatment for BD. Additionally, individuals with BD experience accelerated biological aging. METHODS: We compared blood DNA methylation profiles measured with EPIC v.2.0 arrays between patients with BD (33 lithium responders and 31 nonresponders) and nonpsychiatric controls (n = 32), as well as based on long-term lithium response. In addition, we compared cellular aging between these groups using epigenetic age, pace of aging, and, for the first time, transcriptional age acceleration based on bulk RNA sequencing in 93 patients and 56 controls. RESULTS: We identified 191 differentially methylated positions (DMPs) and 8 differentially methylated regions between patients with BD and controls, located in genes enriched for "Postsynaptic Density" (odds ratio = 6.81, p = 0.001). No DMP was significantly associated with lithium response after multiple testing correction. Patients showed a significantly higher biological age acceleration than controls based on two epigenetic clocks (GrimAge, Mann-Whitney U = 551, p = 0.0009; GrimAge2: U = 477, p = 9.0E-05) and pace of aging (DunedinPACE, t = 3.01, p = 0.003), but not on transcriptional age. While we observed no significant difference in epigenetic aging based on lithium response, lithium responders showed lower epigenetic acceleration using all clocks, with a trend observed using the PhenoAge clock (t = 1.97, p = 0.053). CONCLUSIONS: Our findings point to methylation patterns characterizing BD and support the hypothesis of accelerated cellular aging in BD.

Humans↗
PubMed1979

Chemical synthesis of three 14 alpha-hydroxymethyl cholestenols.

Reported herein are chemical syntheses of 14 alpha-hydroxymethyl-5 alpha-cholest-8-en-3 beta-ol, 14 alpha-hydroxymethyl-5 alph-cholest-7-en-3 beta-ol, and 14 alpha-hydroxymethyl-5 alpha-cholest-6-en 3 beta-ol. These compounds were obtained in pure form after repeated medium-pressure column chromatography of the mixture obtained by treatment of 3 beta-acetoxy-7 alpha,32-epoxy-14 alpha-methyl-5 alpha-cholestane with pyridine hydrochloride in refluxing acetic anhydride followed by reduction with lithium aluminum hydride. The compounds were characterized by their chromatographic properties and by the results of infrared, optical rotation, nuclear magnetic resonance, and low and high resolution mass spectral studies.

Cholestenes↗