Diets with no or low amounts of dietary fiber can reduce small intestinal ulcers induced by non-steroidal anti-inflammatory drugs in dogs.

Recent progress in endoscopic techniques has revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but effective therapy is not available at present. In the present study, we investigated the effects of feeding condition and the amount of dietary fiber (DF) in the diet on the formation of gastrointestinal ulcers induced by NSAIDs in dogs. Several types of diets containing various percentages of DF were given to dogs. Indomethacin (1 or 3 mg/kg, p.o.), ketoprofen (2 mg/kg, s.c.), or fulnixin (1 mg/kg, s.c.) was administered once daily at 10 a.m. after a morning meal or without a morning meal (fasted condition) for 3 - 7 days. Gastrointestinal lesions were examined 24 h after the final dose of the drugs. When indomethacin (3 mg/kg) was administered after a morning meal (fed condition) for 7 days, it produced many lesions in the small intestine. However, when it was given in the fasted condition without the morning meal, the lesions were markedly decreased. All the NSAIDs given after feeding of regular dry food containing 6% DF once a day for 3 days produced many lesions in the small intestine. The lesions were decreased or increased in dogs given prescription diets containing low DF (1.1%) and high DF (15.4%), respectively. Furthermore, lesions were not observed in dogs given canned diet containing very low DF (< 0.1%), whereas lesions appeared again in dogs given canned diet supplemented with cellulose (3 or 10%) but not with pectin (10%). These results suggested that both feeding condition and insoluble DF, such as cellulose in the diet, play an important role in the formation of NSAID-induced small intestinal lesions, and that a diet with no or low amounts of DF may decrease gastrointestinal side-effects associated with the use of NSAIDs.

Tuberothalamic artery infarctions following coil embolization of ruptured posterior communicating artery aneurysms with posterior communicating artery sacrifice.

BACKGROUND AND PURPOSE: Ischemic complications after coil embolization of the PcomA aneurysms are not thoroughly understood, especially in cases in which the PcomA is sacrificed. Our purpose was to examine the preoperative angiographic features and pattern of postoperative cerebral infarctions exhibited by patients who underwent embolization of ruptured PcomA aneurysms with PcomA sacrifice. MATERIALS AND METHODS: A retrospective review identified 14 patients with ruptured PcomA aneurysms who underwent embolization of the aneurysms in combination with PcomA sacrifice. Preoperative angiographic data, including the Allcock test, postoperative DWI, and neurologic status, were examined. RESULTS: Elimination of the aneurysm was complete in all cases. Postoperative DWI indicated 7 cases with infarctions (infarction group) and 7 cases without infarctions (noninfarction group). All patients in the infarction group developed infarctions in the vicinity of the tuberothalamic artery. In all 14 cases, a preoperative Allcock test demonstrated a retrograde filling of the PcomA through the P1 segment. The incidence of negative visualizations of the P1 segment on vertebral angiograms was significantly higher in the infarction group (100%) than in the noninfarction group (0%; P = .00058). The mean PcomA diameters, PcomA/P1 ratios, and aneurysm sizes observed in the infarction group were significantly greater than those in the noninfarction group (P < .05, P < .01, and P < .02, respectively). Tuberothalamic artery infarction caused hemiparesis and memory disturbance, which were associated with unfavorable outcomes. CONCLUSIONS: After the coil occlusion of ruptured PcomA aneurysms with PcomA sacrifice, tuberothalamic artery infarctions tended to occur in cases exhibiting negative visualization of the P1 segment, even when collateral flow was observed with the Allcock test.

Antibacterial activity and clinical efficacy of sparfloxacin in Mycobacterium avium-intracellulare complex infection.

In Japan the incidence of atypical mycobacteriosis has steadily increased, with Mycobacterium avium-intracellulare complex (MAC) the most common infecting organism. A standard chemotherapy regimen for MAC infection has not been established because of significant resistance to anti-mycobacterial drugs. Sparfloxacin has good antimicrobial activity against several acid-fast bacteria and is expected to be an effective drug for treating mycobacteriosis. We examined the effects of adding sparfloxacin to anti-tuberculotic combination therapy in six patients with MAC pulmonary disease. Drug susceptibility was also assessed using the agar dilution method. The minimum inhibitory concentrations (MICs) for sparfloxacin, levofloxacin, isoniazid, rifampicin, streptomycin, ethambutol and clarithromycin was measured in clinical isolates from all patients; sparfloxacin showed the lowest MIC. Bacteriological and clinical improvements were observed in the four patients who completed the study. Dosing was discontinued in two patients because of pruritic skin eruptions. Sparfloxacin shows promise as an anti-mycobacterial agent for treating MAC pulmonary disease.

Steroid 5alpha-reductase inhibitory activity and hair regrowth effects of an extract from Boehmeria nipononivea.

The acetone extract of Boehmeria nipononivea showed both potent 5alpha-reductase inhibitory activity and hair regrowth promotion effects on mice. 5alpha-Reductase inhibitory activity-guided fractionation led to six active fatty acids: alpha-linolenic, linoleic, palmitic, elaidic, oleic and stearic acids. The extract of B. nipononivea, and alphalinolenic, elaidic and stearic acids exhibited a hair regrowth effect.

Usefulness of serum carboxy-terminal telopeptide of type I collagen (ICTP) as a marker of bone metastasis from lung cancer.

BACKGROUND: Serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) is a metabolite of type I collagen comprising 90% or more of organic substances in bone. Its usefulness as a marker of bone metastasis from malignant tumors is expected. METHOD: We measured ICTP to evaluate its clinical usefulness for diagnosis of bone metastasis in 140 patients with lung cancer. For comparison, serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), gastrin-releasing peptide precursor (ProGRP), alkaline phosphatase and calcium were simultaneously measured. ICTP was measured by double-antibody radioimmunoassay. RESULTS: ICTP was significantly higher in patients with bone metastasis from lung cancer than in the group without bone metastasis, patients with other pulmonary diseases or healthy control subjects and showed excellent sensitivity and specificity, indicating that this marker is highly useful for complementary diagnosis of bone metastasis from lung cancer. Moreover, the survival duration was significantly shorter in the ICTP-positive group than in the ICTP-negative group, suggesting that ICTP can be a prognostic factor in lung cancer. CONCLUSION: It is suggested that measurement of ICTP is worthwhile as a serological diagnostic method of bone metastasis from lung cancer. Moreover, since repeated measurements are possible, this measure was considered very helpful in complementary diagnosis of bone metastasis and also as a standard to determine the timing of examinations such as bone scintigraphy.

Inhibition of tyrosinase by flavonoids, stilbenes and related 4-substituted resorcinols: structure-activity investigations.

Several flavonoids, stilbenes and related 4-substituted resorcinols, obtained from Artocarpus incisus and other plants or synthesized, were tested for their inhibitory activity against tyrosinase. The structure-activity relationships suggested that specific natural or synthesized compounds having the 4-substituted resorcinol skeleton have potent tyrosinase inhibitory ability. Kinetic studies have indicated that specific compounds having the 4-substituted resorcinol skeleton exhibit competitive inhibition of the oxidation of DL-beta-(3,4-dihydroxyphenyl)alanine (DL-DOPA) by mushroom tyrosinase. These findings could lead to the design and discovery of new tyrosinase inhibitors.

The 5 alpha-reductase inhibitory components from heartwood of Artocarpus incisus: structure-activity investigations.

The methanol extract of heartwood of Artocarpus incisus showed potent 5 alpha-reductase inhibitory activity. We investigated the 5 alpha-reductase inhibitory effects of nine compounds isolated from A. incisus. Chlorophorin (IC50 = 37 microM) and artocarpin (IC50 = 85 microM) showed more potent inhibitory effects than did alpha-linolenic acid, which is known as a naturally occurring potent inhibitor. Structure-activity investigations suggested that the presence of an isoprene substituent (prenyl and geranyl) would enhance 5 alpha-reductase inhibitory effects.

The inhibitory components from Artocarpus incisus on melanin biosynthesis.

The inhibitory effects of methanol extracts of heartwood of 23 Papua New Guinean wood species on tyrosinase activity were examined. The extract of Artocarpus incisus showed the strongest tyrosinase inhibitory activity which was equivalent to kojic acid. The extract apparently inhibited melanin biosynthesis of both cultured B16 melanoma cells without any cytotoxicity and in the back of a brown guinea pig without skin irritation. Thus, the potentiality of the extracts of heartwood of A. incisus both as material of a useful skin whitening agent and as a remedy for disturbances in pigmentation is evident. Tyrosinase inhibitory activity-guided fractionation led to the isolation of seven active compounds including a new compound which has been characterized as 6-(3"-methyl-1"-butenyl)-5,7,2',4'-tetrahydroxyflavone, named isoartocarpesin. Other active compounds were (+)-dihydromorin, chlorophorin, (+)-norartocarpanone, 4-prenyloxyresveratrol, artocarbene, and artocarpesin, These compounds are probably responsible for the melanin biosynthesis inhibitory effects.

Peopling of the Americas, founded by four major lineages of mitochondrial DNA.

Nucleotide sequence analysis of the major noncoding region of human mitochondrial DNA from various races was extended with 72 Native Americans from 16 different local populations (nine populations from Chile, four from Colombia, and one each from Brazil and from Maya and Apache Indians). The sequences were determined directly from the polymerase chain reaction products. On the basis of a comparison of the 482-bp sequences in the 72 Native Americans, 43 different types of mitochondrial DNA sequences were observed. The nucleotide diversity within the Native Americans was estimated to be 1.29%, which is slightly less than the value of 1.44% from the total human population including Africans, Europeans, and Asians. Phylogenetic analysis revealed that most Native American lineages are classified into four major distinct clusters. Individuals belonging to each cluster share at least two specific polymorphic sites that are nearly absent in other human populations, indicating a unique phylogenetic position of Native Americans. A phylogenetic tree of 193 individuals including Africans, Europeans, Asians, and Native Americans indicated that the four Native American clusters are distinct and dispersed in the tree. These clusters almost exclusively consist of Native Americans--with only a few Asians, if any. We postulate that four ancestral populations gave rise to different waves of migration to the New World. From the estimated coalescence time of the Asian and Native American lineages, we infer that the first migration across the Bering landbridge took place approximately 14,000-21,000 years ago. Furthermore, sequence differences in all pairwise comparisons of Native Americans showed a bimodal distribution that is significantly different from Poisson. These results suggest that the ancestral Native American population underwent neither a severe bottleneck nor rapid expansion in population size, during the migration of people into the Americas.

Phylogenetic affiliation of ancient and contemporary humans inferred from mitochondrial DNA.

Nucleotide sequence analysis of the major non-coding region of human mitochondrial DNA (mtDNA) from three major races was extended with data from 27 contemporary Mongoloids (20 from southeast Asia, seven from America) and 11 Ancient Japanese bones (five from Jomon Age; 3000-6000 years BP, six from the early modern Ainu; 200-300 years BP). In both cases, the sequence was determined directly from the polymerase chain reaction products. Based on a comparison of the 482 base pair sequences from a total of 128 contemporary humans, the nucleotide diversity is estimated to be 1.46%, which is three times higher than the corresponding value estimated from restriction-enzyme analysis of the whole mtDNA genome. The phylogenetic tree revealed that all lineages are classified into at least five clusters designated as C1-C5. C1 consists exclusively of Africans, and most Asians and Europeans formed C2, C3, C5 and C4, respectively. Phylogenetic analysis also indicated that part of the Asians, including the Japanese, subsequently diverged from the majority of Africans, and that Asians can therefore be separated into two distinct groups. Native Americans, however, appeared only in C3 and C5, suggesting that the size of the founder population was not so large during the peopling of American. Nucleotide sequences derived from ancient bones in a highly polymorphic region were also compared with those of contemporary humans. The nucleotide diversity among the 139 sequences in the region was estimated to be 2.26%. A group of ancient Japanese, including both Jomon peoples and the Ainu, showed a close phylogenetic affiliation with one group of contemporary Japanese and southeast Asians.(ABSTRACT TRUNCATED AT 250 WORDS)