New ghrelin agonist, HM01 alleviates constipation and L-dopa-delayed gastric emptying in 6-hydroxydopamine rat model of Parkinson's disease.

BACKGROUND: Constipation and L-dopa-induced gastric dysmotility are common gastrointestinal (GI) symptoms in Parkinson's disease (PD). We investigated the novel ghrelin agonist, HM01 influence on GI motor dysfunctions in 6-hydroxydopamine (6-OHDA) rats. METHODS: HM01 pharmacological profiles were determined in vitro and in vivo in rats. We assessed changes in fecal output and water content, and gastric emptying (GE) in 6-OHDA rats treated with orogastric (og) HM01 and L-dopa/carbidopa (LD/CD, 20/2 mg/kg). Fos immunoreactivity (ir) cells in specific brain and lumbosacral spinal cord were quantified. KEY RESULTS: HM01 displayed a high binding affinity to ghrelin receptor (Ki: 1.42 ± 0.36 nM), 4.3 ± 1.0 h half-life and high brain/plasma ratio. 6-OHDA rats had reduced daily fecal output (22%) and water intake (23%) compared to controls. HM01 (3 and 10 mg/kg) similarly reversed the decreased 4-h fecal weight and water content in 6-OHDA rats. Basal GE was not modified in 6-OHDA rats, however, LD/CD (once or daily for 8 days) delayed GE in 6-OHDA and control rats that was prevented by HM01 (3 mg/kg acute or daily before LD/CD). HM01 increased Fos-ir cell number in the area postrema, arcuate nucleus, nucleus tractus solitarius, and lumbosacral intermediolateral column of 6-OHDA rats where 6-OHDA had a lowering effect compared to controls. CONCLUSIONS & INFERENCES: 6-OHDA rats display constipation- and adipsia-like features of PD and L-dopa-inhibited GE. The new orally active ghrelin agonist, HM01 crosses the blood-brain barrier and alleviates these alterations suggesting a potential benefit for PD with GI disorders.

Determination of hepatitis delta virus (HDV)-RNA in asymptomatic cases of HDV infection.

OBJECTIVES: To assess the frequency of hepatitis delta virus (HDV) viremia in asymptomatic cases of HDV infection and the clinical significance of the HDV viremia, we conducted a cross-sectional, community-based study. METHODS: Of 2207 examinees, 210 (9.5%) were found to be positive for hepatitis B surface antigen (HBsAg). Antibody to HDV was detected in 47 (22.4%) of the 210 examinees, and 43 of the 47 were further evaluated for serum HDV-RNA by polymerase chain reaction. RESULTS: Twenty-one (48.8%) of the 43 had detectable levels of HDV-RNA in serum, and 22 (51.2%) were negative for serum HDV-RNA. The majority (61.9%) of the HDV-RNA-positive HBsAg carriers had high levels of serum ALT. In contrast, the frequency of an abnormally high level of serum ALT was only 9.1% in the HBsAg carriers positive for HDV antibody but negative for HDV-RNA, and the frequency did not differ from that seen in the HBsAg-negative individuals. The semiquantified HDV-RNA levels did not correlate with the serum ALT levels. CONCLUSION: Seropositivity of HDV-RNA was strongly associated with liver cell damage, even in asymptomatic cases. The absence of a detectable level of serum HDV-RNA might be related to previous HDV infection.

High proportion of false positive reactions among donors with anti-HCV antibodies in a low prevalence area.

Among 39,656 voluntary blood donors in Okinawa Prefecture, Japan, 115 (0.29%) were repeatedly reactive for antibody to hepatitis C virus (anti-HCV) by second generation (2nd-gen) passive hemagglutination assay (PHA). Positive serum samples were tested for anti-HCV using three different enzyme immunosorbent assays (ELISAs; Abbott 2nd EIA, UBI-HCV-EIA, JCC-2) and for HCV-RNA by the polymerase chain reaction (PCR). The 115 2nd-gen PHA-positive sera were divided into three groups according to the agglutination titers; > 2(10) (high titer group), 2(7)-2(9) (median), 2(5)-2(6) (low). All but one serum (44/45) in the high PHA titer group reacted in each of the three second screening ELISAs. Furthermore, 43 (97.7%) of the 44 sera contained HCV-RNA by PCR. In the median titer group, 11 of the 13 samples tested were positive by each of the three ELISAs, and 4 (36.4%) of the 11 showed reaction by PCR. On the other hand, all of the 38 sera tested in the low titer group were negative for HCV-RNA by PCR, and 24 of the 38 were also negative by each of the three ELISAs. Most of the low titer positive reactions in the 2nd-gen agglutination assay seemed to be false positive. In Okinawa Prefecture, the prevalence of anti-HCV among blood donors is much lower than in the rest of Japan (0.29% vs. 1.11%). Moreover, a significant proportion of these sera were low titer by the PHA assay.(ABSTRACT TRUNCATED AT 250 WORDS)