Effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for hemorrhoidal symptoms: a prospective, observational study.

BACKGROUND AND AIMS: A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice. METHODS: Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined. RESULTS: Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated. CONCLUSIONS: The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.

Reorganization of synaptic inputs to the hypothalamic paraventricular nucleus during chronic psychogenic stress in rats.

BACKGROUND: Chronic stress in humans precipitates hyper-reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis and triggers symptoms associated with certain forms of depression. Reorganization of neuronal networks has been implicated in development of depression, however it remained unknown how chronic exposure to psychogenic challenges affects excitatory and inhibitory inputs to corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus that govern neuroendocrine stress response. METHODS: Rats (n = 32) were exposed for 21 days to chronic variable stress and their behavioral (sucrose preference) and hormonal (corticosterone) responses were followed together with electron microscopic stereologic analysis of excitatory and gamma-aminobutyric acid (GABA)-containing, inhibitory synapses on the CRH synthesizing neurons. RESULTS: Chronic stress in rats resulted in weight loss, anhedonia, and hyperactivity of hypothalamic-pituitary-adrenocortical axis. Following 3 weeks' exposure to variable psychologic stressors the number of synapses has been doubled in the paraventricular nucleus. Asymmetrical excitatory as well as GABAergic inhibitory synaptic contacts were increased on CRH neurons; however, the excitatory/inhibitory input ratio remained constant. In response to chronic stress, we found rearrangement of inhibitory GABA-containing inputs with the increase of contacts on dendrites and decrease at the soma region of CRH neurons. CONCLUSIONS: Significant remodeling of synaptic contacts was found on CRH neurons in response to chronic stress. This morphologic plasticity might be related to the hyperactivity of the HPA axis and to development of stress-related psychopathologies such as depression.

Hyperleptinemia, visceral adiposity, and decreased glucose tolerance in mice with a targeted disruption of the histidine decarboxylase gene.

Histamine has been referred to as an anorexic factor that decreases appetite and fat accumulation and affects feeding behavior. Tuberomammillary histaminergic neurons have been implicated in central mediation of peripheral metabolic signals such as leptin, and centrally released histamine inhibits ob gene expression. Here we have characterized the metabolic phenotype of mice that completely lack the ability to produce histamine because of targeted disruption of the key enzyme in histamine biosynthesis (histidine decarboxylase, HDC). Histochemical analyses confirmed the lack of HDC mRNA, histamine immunoreactivity, and histaminergic innervation throughout the brain of gene knockout mouse. Aged histamine-deficient (HDC-/-) mice are characterized by visceral adiposity, increased amount of brown adipose tissue, impaired glucose tolerance, hyperinsulinemia, and hyperleptinemia. Histamine-deficient animals are not hyperphagic but gain more weight and are calorically more efficient than wild-type controls. These metabolic changes presumably are due to the impaired regulatory loop between leptin and hypothalamic histamine that results in orexigenic dominance through decreased energy expenditure, attenuated ability to induce uncoupling protein-1 mRNA in the brown adipose tissue and defect in mobilizing energy stores. Our results further support the role of histamine in regulation of energy homeostasis.