Does loneliness before the age of twelve indirectly affect impaired control over drinking, alcohol use, and problems through perceived stress?

Loneliness is the pain of feeling socially isolated from others (Russell et al., 1980). The Stress-Dampening Hypothesis (Marlatt, 1987; Sayette, 1993; Sher, 1987) posits that individuals drink to alleviate negative affect. To date, it has not been determined whether loneliness experienced as a child can indirectly influence at-risk patterns of alcohol use through the mediating mechanism of stress and impaired control. Impaired control over alcohol use (IC) is the difficulty adhering to one's own self-proscribed limits on drinking behaviors (Heather et al., 1993). Impaired control is an at-risk pattern of use that is particularly relevant to emerging adults. Methods: We examined the direct and indirect relationships between childhood loneliness, stress, IC, and alcohol-related problems with a structural equation model. In a college student sample, we utilized a (k = 20,000) bootstrap technique and a model indirect command in Mplus to examine potential mediational pathways. Cisgender sex was included as a covariate. Results: Loneliness was directly linked to stress as well as to alcohol-related problems. Higher levels of loneliness were indirectly linked to both more alcohol use and alcohol-related problems through more stress and in turn, more impaired control over drinking. Conclusions: The current study is consistent with the Stress Dampening Hypothesis (Marlatt, 1987; Sayette, 1993; Sher, 1987). Our findings suggest that therapeutic interventions combating loneliness in childhood may disrupt the stress-dampening pathway to dysregulated alcohol use in emerging adulthood.

Synthesis, in vitro binding profile, and autoradiographic analysis of [3H]-cis-3-[(2-methoxybenzyl)amino]-2-phenylpiperidine, a highly potent and selective nonpeptide substance P receptor antagonist radioligand.

The synthesis of a highly potent and selective NK1 receptor antagonist radioligand, [3H]-cis-3-[(2-methoxybenzyl)amino]-2-phenylpiperidine (6a) is described. The in vitro binding pharmacology and autoradiographic distribution of 6a in guinea pig brain following peripheral administration are also reported.

(6R,8S)-(2-benzimidazolyl)hydroxymethylpenicillanic acids as potent antibacterial agents and beta-lactamase inhibitors.

(6R,8S)-(2-Benzimidazolyl)hydroxymethylpenicillanic acids (1a-1x) are potent antibacterial agents and beta-lactamase inhibitors against Gram-positive bacteria and Haemophilus influenzae. The corresponding (6R,8R)-isomers (2a-2x), the 6,6-spiro benzimidazole-penam alcohol (3), (7R,9S)-(2-benzimidazolyl)hydroxymethylcephalosporanic acid (4), and 6 beta-(2-benzimidazolyl)aminopenicillanic acid (5) are much less active as antibacterials or beta-lactamase inhibitors. The syntheses and structure-activity relationships of these compounds are discussed. Antibacterial activity and beta-lactamase inhibition data are presented.

Synthesis, in vitro binding profile, and central nervous system penetrability of the highly potent 5-HT3 receptor antagonist [3H]-4-(2-methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole.

4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with this radioligand indicate that it effectively penetrates the blood-brain barrier upon peripheral administration. Thus, 5 should be a useful pharmacological tool for both in vitro and in vivo studies of this class of compounds.

Thiazole as a carbonyl bioisostere. A novel class of highly potent and selective 5-HT3 receptor antagonists.

A novel structural class of highly potent and selective 5-HT3 receptor antagonists is described. The compounds in this new series contain a thiazole moiety linking an aromatic group and a nitrogen-containing basic region; the thiazole group appears to be acting as a carbonyl bioisostere in this system. An optimized member of this series, 4-(2-methoxyphenyl)-2-[[4(5)-methyl-5(4)-imidazolyl]methyl]thiazole (5), exhibits oral activity in the Bezold-Jarisch reflex paradigm comparable to or better than the standard agents ondansetron (1) and ICS-205-930 (2). Several of the structure-activity relationships are rationalized in terms of a computer pharmacophore model for 5-HT3 receptor binding.

Structure-activity relationships of 6-(heterocyclyl)-methylene penam sulfones; a new class of beta-lactamase inhibitors.

6-(Heterocyclyl)methylene penam sulfones (1) are effective beta-lactamase inhibitors and potent ampicillin and cefazolin potentiators against both Gram-positive and Gram-negative beta-lactamase producing bacteria. Several of these analogs having a pi-deficient 2-heteroaryl substituent attached to the C6-methylene position showed better inhibitory activity than clavulanic acid, Ro 15-1903, 6 beta-bromopenicillanic acid, and sulbactam against a variety of beta-lactamases. The compounds were devoid of any antibacterial activity, but in combination with ampicillin or cefazolin, exhibited synergistic activity at least equal to clavulanic acid, Ro 15-1903, 6 beta-bromopenicillanic acid or sulbactam against beta-lactamase producing strains. Structure-activity relationships for a number of compounds are described. The structure-activity relationships can be rationalized by an enzyme inhibition mechanism which we have previously proposed on the basis of methanolysis of 6-(2-pyridyl)methylene penam sulfone (1a). Two synthetic routes to prepare compounds of structural type 1 via either a Wittig reaction or an aldol condensation are reported. beta-Lactamase inhibition and MIC data are presented.

Enhancement of the luminol test by means of light amplification.

The type of device commonly referred to as a "starlight scope" will amplify available light by a factor of approximately 17 000. The use of this device will permit an image to be formed by exceedingly small amounts of blood when reacted with luminol reagent. Modification of the apparatus is necessary to permit focusing at short distances.