Barriers to the use of medications to treat alcoholism

In 1994, naltrexone became the first medication approved by the Food and Drug Administration as an adjunct in alcoholism treatment in almost fifty years. Despite evidence of its efficacy, use of naltrexone is not widespread. Patient and physician focus groups were used to identify reasons naltrexone has not been prescribed more widely. Barriers to its widespread use include a lack of awareness, a lack of evidence of efficacy in practice, side effects, time for patient management, a reluctance to take medications, medication addiction concerns, Alcoholics Anonymous (AA) philosophy, and price. The study indicates that medications to treat alcoholism must overcome numerous barriers before becoming widely accepted.     

Social exploitation of vitellogenin

Vitellogenin is a female-specific glucolipoprotein yolk precursor produced by all oviparous animals. Vitellogenin expression is under hormonal control, and the protein is generally synthesized directly before yolk deposition. In the honeybee (Apis mellifera), vitellogenin is not only synthesized by the reproductive queen, but also by the functionally sterile workers. In summer, the worker population consists of a hive bee group performing a multitude of tasks including nursing inside the nest, and a forager group specialized in collecting nectar, pollen, water, and propolis. Vitellogenin is synthesized in large quantities by hive bees. When hive bees develop into foragers, their juvenile hormone titers increase, and this causes cessation of their vitellogenin production. This inverse relationship between vitellogenin synthesis and juvenile hormone is opposite to the norm in insects, and the underlying proximate processes and life-history reasons are still not understood. Here we document an alternative use of vitellogenin by showing that it is a source for the proteinaceous royal jelly that is produced by the hive bees. Hive bees use the jelly to feed larvae, queen, workers, and drones. This finding suggests that the evolution of a brood-rearing worker class and a specialized forager class in an advanced eusocial insect society has been directed by an alternative utilization of yolk protein.     

Effects of interferon-α2b treatment on ex vivo differentiation of mast cells from circulating progenitor cells in a patient with systemic mastocytosis

 Interferon (IFN)-α, a known inhibitor of myelopoiesis, is increasingly used to treat patients with systemic mastocytosis (SM). However, the mechanisms of IFN-α effects on mast cell (MC) growth remain unknown, and the treatment responses may be variable. In the present study, factor-dependent ex vivo differentiation of MCs from peripheral blood mononuclear cells (PBMNCs) was analyzed in a patient with SM treated with IFN-α2b (3 million U/day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to >1400 ng/ml). PBMNCs were collected before and during IFN-α2b treatment and cultured in the presence or absence of stem cell factor (SCF, 100 ng/ml) for 42 days. In the absence of SCF, no MC growth was detectable. However, in the presence of SCF, MC containing tryptase appeared in the cultures. Treatment with IFN-α2b resulted in a time-dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-α2b treatment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-α2b treatment. However, after a latency period of a few months, tryptase concentrations declined and then reached a plateau. In healthy individuals, the SCF-induced in vitro growth of MCs from their progenitor cells was also inhibitable by the addition of IFN-α2b. In summary, our data show that IFN-α2b can exhibit inhibitory effects on factor-dependent growth of MC progenitor cells. However, it still remains open which of the patients with mastocytosis can benefit from long-term IFN-α treatment. Received: 19 January 2000 / Accepted: 17 April 2000     

Idiopathic myointimal hyperplasia of mesenteric veins: a rare mimic of idiopathic inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood disease that occurs in the rectosigmoid colon of predominantly young, previously healthy male patients. IMHMV typically requires segmental resection due to complications after a relatively protracted clinical course. This disease presents a challenging diagnostic dilemma for the clinician because it is initially often confused with chronic idiopathic inflammatory bowel disease. We report a case of IMHMV, illustrate endoscopic and histopathologic features, and review key characteristics of this rare entity.     

Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome

BACKGROUND & AIMS: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. METHODS: Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. RESULTS: Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.