Therapeutic rationale for low dose doxepin in insomnia patients

Histamine is an excitatory neurotransmitter in central nervous system. It plays an important role in the regulation of the sleep-wake cycle. Antidepressant with sleep-promoting effects, for example, doxepin, promotes sleep not through a sedative action but through resynchronisation of circadian cycle. The stimulation of the H1 receptor is thought to play an important role in mediating arousal. Doxepin has a high affinity for the H1 receptor, making it a selective H1 antagonist at low dose and it has been shown to display sedating properties. Compared to other sedative antidepressant, low dose doxepin is the only tricyclic drug which has been evaluated by well-designed, randomised, double blind, placebo controlled studies in both adult and elderly patients. Doxepin is not designated as controlled substance/unscheduled drugs and thus may be of special advantage to use in patients with a history of substance abuse. Hence, well-documented therapeutic efficacy, tolerability and lack of important adverse effects make the low dose doxepin as a unique, rational drug for the treatment of insomnia in adult and elderly patients.     

Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity

Viremia titers in serial plasma samples from 168 children with acute dengue virus infection who were enrolled in a prospective study at 2 hospitals in Thailand were examined to determine the role of virus load in the pathogenesis of dengue hemorrhagic fever (DHF). The infecting virus serotype was identified for 165 patients (DEN-1, 46 patients; DEN-2, 47 patients; DEN-3, 47 patients, DEN-4, 25 patients). Patients with DEN-2 infections experienced more severe disease than those infected with other serotypes. Eighty-one percent of patients experienced a secondary dengue virus infection that was associated with more severe disease. Viremia titers were determined for 41 DEN-1 and 46 DEN-2 patients. Higher peak titers were associated with increased disease severity for the 31 patients with a peak titer identified (mean titer of 107.6 for those with dengue fever vs. 108.5 for patients with DHF, P=.01). Increased dengue disease severity correlated with high viremia titer, secondary dengue virus infection, and DEN-2 virus type.     

Alcoholic fatty liver: A nutritional problem of carbohydrate deprivation and concomitant ethanol ingestion

Until two decades ago, it was generally considered that malnutrition was primarily responsible for the development of alcohol-induced fatty liver or liver injury. Subsequently, results from experiments with nutritionally adequate liquid alcohol diets created a vogue that ethanol toxicity caused fatty liver and did not address the role of coincident nutritional imbalances. Nutritional inadequacies exist when fatty liver is produced. Furthermore, alcoholic fatty liver is prevented by dietary alteration or supplementation.     

Inadequate intake by growing rats of essential nutrients from liquid diets used for chronic alcohol consumption

In most studies on the biological effects of chronic alcohol ingestion, young rats were fed liquid diets containing 36% calories as ethanol. These diets were considered nutritionally adequate. However, the daily weight gain of alcohol-fed rats is small (2–4 g) as compared to that in rats maintained on an AIN-76 or NIH-07 diet (7 g). Alcohol-fed rats consume not only less calories but also less calcium, copper, iron, manganese, phosphorus and vitamin B₆ than those required for normal growth. A possible deficiency in the intake of other essential nutrients may also exist during chronic alcohol consumption.     

GABA receptor-mediated inhibition of reflex deglutition in the cat

In anesthetized cats, swallowing elicited by electrical stimulation of the superior laryngeal nerves (SLNs) was inhibited by the GABA-mimetic muscimol and by diazepam, an action that was reversed by picrotoxin and bicuculline. This inhibition supports the involvement of GABA receptors, specifically those of the GABA_A subtype which both antagonists have been shown to block in various areas of the central nervous system. The inhibition of reflex swallowing and its reversal were unaltered by a transection of the brainstem at a midcollicular level. Stimulation of the SLNs also caused a bradycardia that was inhibited by both muscimol and diazepam and was restored by both GABA antagonists. Data from these experiments provide suggestive evidence for a role of GABA-ergic transmission in the central control of the deglutitory reflex.