Intestinal permeability and orocaecal transit time in elderly patients with Parkinson's disease.

The aetiology of weight loss in patients with Parkinson''s disease is likely to be multifactorial. We studied 15 patients with Parkinson''s disease and 15 age- and sex-matched controls and looked for evidence of malabsorption due to small bowel bacterial overgrowth or alteration of intestinal permeability. There was a marked increase in orocaecal transit time in the patients with Parkinson''s disease, although lactulose hydrogen breath testing did not show evidence of small bowel bacterial contamination. Intestinal permeability measured by the differential sugar absorption test was also deranged. There was reduced absorption of mannitol in patients with Parkinson''s disease while lactulose absorption was similar in both groups, suggesting decreased non-mediated uptake across the enterocyte brush border membrane in patients with Parkinson''s disease.     

The effect of [Phe(1)psi(CH(2)-NH)Gly(2)]-nociceptin(1-13)NH(2) on feeding and c-Fos immunoreactivity in selected brain sites

Nociceptin/orphanin FQ (N/OFQ) is an endogenous ligand of the ORL1 receptor. N/OFQ, when administered centrally, stimulates feeding in a fashion similar to other opioids. Intracerebroventricular administration of N/OFQ induces changes in c-Fos immunoreactivity in several feeding-related brain sites. A synthetic pseudopeptide, [Phe(1)iota(CH(2)-NH)Gly(2)]-nociceptin(1-13)-NH(2) (hereafter: [FG]N/OFQ(1-13)NH(2)), has been labeled both as an ORL1 agonist and antagonist. The present study was designed to examine the influence of [FG]N/OFQ(1-13)NH(2) on food intake in rats. We also evaluated c-Fos immunoreactivity in those areas of the brain which have been shown to exhibit altered c-Fos expression upon N/OFQ administration. We found that [FG]N/OFQ(1-13)NH(2) increases food consumption in satiated rats. This effect is short-lasting and can be reversed by the opioid antagonist naloxone. Co-administration of [FG]N/OFQ(1-13)NH(2) does not affect orexigenic response to N/OFQ. Intracerebroventricularly-injected [FG]N/OFQ(1-13)NH(2) induces c-Fos expression in the nucleus of the solitary tract, hypothalamic paraventricular and supraoptic nuclei, central nucleus of amygdala, lateral septal and lateral habenular nuclei-brain areas that have been shown to be activated by N/OFQ. These results support the hypothesis that [FG]N/OFQ(1-13)NH(2) acts as an agonist of ORL1 receptor in vivo.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

The effect of chronic ethanol intake on leucine absorption from the rat small intestine

Total (active + diffusion) absorption of leucine from the entire small intestine of rats or from segments of upper jejunum and lower ileum was unaffected by chronic ethanol feeding for 4 weeks. However, because of ethanol-induced mucosal atrophy, specific absorption (expressed per g dry weight of mucosa) was almost doubled in ethanol-fed rats. In the upper jejunum, the active component of leucine uptake was significantly greater in ethanol-fed rats (72% vs. 52%), whereas in the lower ileum the relative contributions of active uptake and diffusion were unaltered. We propose that the increase in active uptake in the upper jejunum is the result of a higher concentration of aged enterocytes having a greater transport capacity at the villus surface.     

Evaluation of a rapid stoolantigen test for the diagnosis of Helicobacter pylori infection in Chinese patients

OBJECTIVE: To evaluate the accuracy of a rapid assay that wasdeveloped to detect Helicobacter pylori antigen in the stool,using the principle of immunochromatography, in the Chinese population. METHODS: Eligible patients without prior treatment of H.pylori were recruited. An in‐house rapid urease test (RUT) andhistology were used as the gold standard. The results of the rapidstool antigen test were compared with the gold standard. RESULTS: Valid rapid stool antigen test results for interpretationwere obtained from 94 consecutive patients (mean age: 52.5, range:22?82 years). Sensitivity, specificity, positive predictivevalue, negative predictive value and accuracy were, respectively, 77.5%,87.0%, 81.6%, 83.9% and 83.0%.The test was easy to perform and results were available within 15 min. CONCLUSION: The rapid stool antigen test using immunochromatography accuratelydiagnoses H. pylori infection in Chinese patients.     

Synthesis and antimycobacterial activity of some heteroarylcarboxamidrazone derivatives.

A series of pyridine-2-, pyrazine-2- and quinoline-2-carboxamidrazone derivatives was prepared in an automated fashion and tested against Mycobacterium fortuitum in a rapid screen. Seven pyridine-2-carboxamidrazone derivatives were investigated further and four were found to have inhibitory activity with compound 4af being the most active. The structure activity implications are discussed.     

Mucocutaneous manifestations in 22 consecutive cases of primary HIV-1 infection

Summary Twenty-two consecutive patients presenting with symptomatic human immunodeficiency virus 1 (HTV-1) seroconversion were studied. Most of the patients had a glandular fever-like illness.
All patients had fever and pharyngitis, and eight of them also suffered from ulcers of the oral, genital or anal mucosa. Uniform skin eruptions were observed in 17 of the 22 patients. The exanthem consisted of varying numbers of macular or maculopapular lesions that were oval or rounded in shape, ranging from a few millimetres to 1 cm in diameter. The lesions were distributed on the upper thorax in all cases, and were particularly profuse in the collar region. The face forehead and scalp were involved in most cases, but the eruption was sparse or absent at the periphery of the extremities. In the majority of patients, the exanthem appeared after 2 or 3 days of fever. The exanthem developed during the first day, persisted for 5-8 days, and then cleared concurrently with the general recovery of the patients.
Histopathological studies of skin punch biopsy specimens from four patients showed a sparse lymphocytic cell infiltrate distributed around vessels of the dermal superficial plexus. The infiltrates predominantly consisted of equally represented T-helper/inducer and T-suppressor/cytotoxic cells. A vacuolar aberration of basal layer cells was found in two of the four eases studied histologically. The microscopic findings correspond to the histopathological patterns seen in toxieodermia and in the interface dermatitis of morbilliform viral exanthems. The exanthem is a frequent and characteristic sign of primary HTV infection, which is further indicated if mucosal ulcers are present.     

Naloxone effects on sucrose-motivated behavior

The opioid system plays an important role in feeding. In general, opioid agonists typically increase feeding and opioid antagonists decrease feeding in nonfood restricted animals. In food restricted animals the effects of these drugs are substantially reduced. Opioid antagonists have shown a marked effectiveness at reducing consumption of sweet foods. Explanations for this robust effect have typically focused on drug induced changes in taste, taste perception, or palatability. The current study relates the effects of the opioid antagonist naloxone on motivation to obtain different sucrose concentrations to the drug's effects on unrestricted sucrose solution consumption. Changes in motivation to respond were assessed under a progressive ratio reinforcement schedule (PR) which required increased response cost for each successive unit of sucrose solution. Motivation, as measured by the PR, increased as sucrose concentration increased and naloxone produced a dose-dependent decrease in motivation to respond for a given sucrose concentration. Thus, the effectiveness of naloxone was indirectly related to strength of the sucrose concentration. Under unrestricted access to sucrose solutions, naloxone reduced consumption greatest under the higher concentrations. The data suggest at least part of naloxone's effects on sweet tasting food may be mediated through endogenous opioid reward systems that are reflected in measures of motivation.