Cognitive impairment and infectious burden in the elderly
ARCHIVES OF GERONTOLOGY AND GERIATRICS
Authors: Strandberg, TE; Pitkala, KH; Linnavuori, K; Tilvis, RS
Abstract
Infectious agents have been suspected as contributing factors to dementia, especially in Alzheimer disease. We intended to test whether viral or bacterial seropositivity is associated with cognitive impairment among home-dwelling elderly. Viral burden (seropositivity for herpes simplex type 1 (HSV1), type 2 (HSV2), or cytomegalovirus (CMV), and bacterial burden (Chlamydia pneumoniae and Mycoplasma pneumoniae) were tested among 383 home-dwelling individuals with vascular disease (mainly coronary heart disease) in the ongoing DEBATE study (mean age 80 years). Mini-mental state examination (MMSE) and its changes were used to define cognitive impairment. At baseline, 0-1, 2, and 3 positive titers toward viruses were found in 48 (12.5 %), 229 (59.8 %), and 106 (27.7 %) individuals, respectively. MMSE points decreased with increasing viral burden (p = 0.03). At baseline, 58 individuals (15.1 %) had cognitive impairment (MMSE < 24 points) which after adjustments was significantly associated with seropositivity for 3 viruses (risk ratio 2.5, 95 % confidence interval 1.3 to 4.7). MMSE score decreased in 150 cases (43 %) during 12-month follow-up. After adjustment for MMSE score at baseline and with 0-1 seropositivities as reference (1.0), the risk ratios were 1.8 (95 % confidence interval 0.9 to 3.6) and 2.3 (95 % confidence interval. 1.1 to 5.0) for 2 and 3 seropositivities, respectively. No significant associations were observed between bacterial burden and cognition. Viral burden of herpesvirus and cytomegalovirus was associated with cognitive impairment in home-dwelling elderly. The association may offer a preventable cause of cognitive decline.
A new synthesis of biologically active pyrroles: Formal synthesis of pentabromopseudilin, bimetopyrol, and several antitubercular agents
JOURNAL OF HETEROCYCLIC CHEMISTRY
Authors: Karimi, Sasan; Ma, Shuai; Qu, Michelle; Chen, Biling; Ramig, Keith; Greer, Edyta M.; Szalda, David J.; Neary, Michelle C.; Berkowitz, William F.; Subramaniam, Gopal
Abstract
Although pyrroles have been synthesized from azido dienes, the corresponding reactions of structurally similar nitrodienes had not been investigated until it became the main focus of this study. This article describes the synthesis of several biologically active pyrroles and mechanistically intriguing results in connection with our new approach using nitrodienes in the presence of Ph3P and a Mo catalyst, bis (acetylaceto)dioxomolybdenum (VI). The final precursor of pentabromopseudilin (PBP), pseudilin, was synthesized in four steps from o-hydroxycinnamaldehyde. An alternate pathway to PBP proceeded through o-methylpseudilin, prepared in two steps from o-methoxycinnamaldehyde. Both starting materials are commercially available. Similarly, bimetopyrol (2-methyl-4,5-bis(p-methoxyphenyl)pyrrole), a potent anti-inflammatory, was prepared using the new methodology. The remarkable conversion of nitrodienes 14 and 15 to bimetopyrol highlights the formation of a nitroso or nitrene intermediate. We also established that 14 and 15 interconvert in the presence of ambient light and each converts to bimetopyrol when reacted separately. The wide application of our synthetic methodology includes preparation of several antitubercular and Herpes Simplex 2 (HSV2) agents.