Effects of oral administration of timothy hay and psyllium on the growth performance and fecal microbiota of preweaning calves.

The objective of this study was to evaluate the effects of oral administration of fiber from the first week of life on the growth and hindgut environment of preweaning calves. Twenty newborn female Holstein calves were divided into 2 groups as control and treatment. Calves in both groups were reared under the same feeding program except for oral fiber administration. Timothy hay and psyllium were mixed at a 50-to-6 ratio as a treatment diet for oral fiber administration. Calves in the treatment group were orally administered 50 g of fiber daily from 3 to 7 d of age and 100 g of fiber from 8 d of age until weaning. Feed intake and occurrence of diarrhea were recorded daily, and body weight (BW) was recorded weekly for the individual calf. Fresh feces were collected from calves at 7, 21, 35, 49, and 56 d of age to analyze fermentation parameters and microbiota to characterize the hindgut environment. Higher fiber intake in the treatment group due to oral administration of timothy and psyllium did not affect the starter intake and achieved higher BW at 21 d of age. The fecal pH, total volatile fatty acid, lactate, and ammonia nitrogen concentrations were not affected by oral fiber administration; meanwhile, the molar proportion of propionate was higher in the treatment group at 7 d of age. The difference in fecal microbiota in the calves subjected to the oral administration of fiber was observed within 21 d of life; Lactobacillus spp. and Prevotella spp. showed higher abundance, whereas that of Clostridium perfringens was decreased. These higher abundances of beneficial bacteria and lower abundance of pathogenic bacteria during early life may partly explain the higher BW of calves in the treatment group at 21 d of age. Furthermore, no adverse effect was observed for the BW and health status in the treatment group throughout the preweaning period. Therefore, early fiber feeding via oral administration potentially contributes to improving the hindgut environment in newborn calves, which leads to better growth of calves during the early stage of life.

Cellulose acetate, a new candidate feed supplement for ruminant animals: In vitro evaluations.

Cellulose acetate (CA), a derivative of cellulose in which some hydroxyl groups are substituted with acetyl groups, was evaluated as a new cellulosic feed source for ruminants. In the present work, a series of in vitro studies was carried out to determine how CA supplementation affects rumen fermentation and microbiota. Batch culture studies were conducted to select the type of CA suitable for feed use and to define the optimal supplementation level. Rumen fluid from 2 Holstein cows was mixed with McDougall's buffer in test tubes into which grass hay and concentrate containing a fiber source [cellulose (control), water-soluble CA (WSCA), or insoluble CA] had been placed. Each fiber source was supplemented at 10% of total substrate. Tubes were incubated for 24 h to determine fermentation and microbial parameters. Then, the dose response of these parameters to different supplementation levels of WSCA (0, 7.5, 15, 22.5, and 30%) was tested in the same manner. We also operated a continuous culture system with WSCA supplementation and evaluated the effects on digestibility, fermentation, and microbial parameters. The supplementation level of WSCA was set at 15% of total feed. In batch culture studies, WSCA, but not insoluble CA, yielded dose-dependent increases in ruminal acetate levels. In the continuous culture system study, WSCA yielded increases in ruminal acetate levels and in the abundance of bacteria of the genus Prevotella, including Prevotella ruminicola. Dry matter digestibility and total gas production were not affected. These results suggest that WSCA supplementation at 15% of total feed yielded increased acetate levels without negatively affecting feed digestion; these effects may reflect activation of Prevotella species. As ruminal acetate is involved in milk fat synthesis, WSCA can be considered as a candidate feed additive suitable for dairy cattle.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

In vitro evaluation of cashew nut shell liquid as a methane-inhibiting and propionate-enhancing agent for ruminants.

Cashew nut shell liquid (CNSL) containing antibacterial phenolic compounds was evaluated for its potency as a feed additive for ruminants. In experiment 1, ruminal responses to CNSL supplementation were assessed using a batch culture system. Rumen fluid from cattle was diluted with artificial saliva and incubated for 18h in a batch culture with a mixed diet containing a 30:70 hay:concentrate diet to which raw or heated CNSL was added at a final concentration of 500 µg/mL. In experiment 2, a Rusitec, using rumen fluid from the same cattle, was operated over a period of 7 d during which only raw CNSL was tested at concentrations of 0, 50, 100, or 200 µg/mL, and variations in fermentation and bacterial population were assessed. In experiment 3, a pure culture study was conducted using selected bacteria to determine their susceptibility to CNSL. In experiment 1, methane production was inhibited by raw CNSL (56.9% inhibition) but not by heated CNSL. Total volatile fatty acid concentration was not affected, whereas increased concentrations of propionate and decreased concentrations of acetate and butyrate were observed using either raw or heated CNSL. These changes were more obvious when raw CNSL was tested. In experiment 2, raw CNSL inhibited methanogenesis and increased propionate production in a dose-dependent manner, showing maximum methane inhibition (70.1%) and propionate enhancement (44.4%) at 200 µg/mL supplementation. Raw CNSL increased total volatile fatty acid concentration and dry matter digestibility. Raw CNSL also appeared to induce a dramatic shift in the population of rumen microbiota, based on decreased protozoa numbers and changes in quantitative PCR assay values for representative bacterial species. In experiment 3, using pure cultures, raw CNSL prevented the growth of hydrogen-, formate-, and butyrate-producing rumen bacteria, but not the growth of bacteria involved in propionate production. Based on these data, raw CNSL, rich in the antibacterial phenolic compound anacardic acid, is a potential candidate feed additive with selective activity against rumen microbes, leading to fermentation that results in decreased methane and enhanced propionate production.

[Use of passing intestine pump (EN) from home ingredient nutrition passing pipe nutrition method (HEN) in home medical treatment support].

Introducing the passing intestine pump (EN) into home medical treatment from October 1999 for passing intestine nutrition management, and to the passing intestine nutrition management to the management is thought to increase the quality of life (QOL) of the patient and the family. The life style of the patient broadens and this seems to be an effective piece of home support equipment. We here in report the actual general management of the passing intestine pump in home medical treatment.

First Report of Powdery Mildew Caused by Podosphaera (Sphaerotheca) fusca on Euryops pectinatus in North America.

Gray-leaved Euryops (Euryops pectinatus Cass., Asteraceae) is an evergreen shrub that is widely planted in landscapes in the United States. In the fall of 1999, powdery mildew was observed on E. pectinatus planted in landscapes in Redlands (San Bernardino County), CA. Symptoms consisted only of slight cupping of leaves. Fungal growth was observed on stems, leaves, petioles, and pedicels and was ectophytic and amphigenous. The white mycelium was patchy to effuse. Hyphal appressoria were indistinct (1). Conidiophore foot cells were cylindric and sometimes were tapered toward or constricted at the base. Foot cells measured 30 to 50 by 10 to 12 µm and were followed by one to two shorter cells. Conidia were cylindric to slightly doliform, borne in chains of two to three, and measured 26 to 38 by 14 to 18 µm. Conidial length to width ratios ranged from 1.7 to 2.4. Catenate conidia had crenate edge lines (3). Conidia possessed conspicuous fibrosin bodies and from their sides produced short germ tubes without appressoria. Cleistothecia were not observed. Based on these characters, the fungus was identified as Podosphaera fusca (Fr.) U. Braun & N. Shishkoff (Podosphaera sect. Sphaerotheca) (1,2). Pathogenicity was confirmed by gently pressing diseased leaves onto leaves of healthy E. pectinatus plants. Plants were incubated in a humidity chamber at 22 to 24°C and after 12 to 14 days powdery mildew colonies developed. E. pectinatus cv. Viridis, a cultivar that lacks the extensive pubescence of E. pectinatus, also developed disease when inoculated. This appears to be the first report of powdery mildew on E. pectinatus in North America. A voucher specimen has been deposited into the University of California Herbarium (accession # UC1738635). P. fusca was also observed on cv. Viridis in a nursery in New York in 1999. It is unclear where this pathogen originated. P. fusca parasitizes a large number of asteraceous species including dandelion (Taraxacum officinalis) and sowthistle (Sonchus spp.) weeds, which occur in the area and sometimes are infected with powdery mildew. The Euryops powdery mildew pathogen may be a race that is different than those found on other composites in the United States. The fungus was observed on plants in shaded areas but not on plants in full sun. References: (1) U. Braun. Nova Hedwigia 89:1, 1987. (2) U. Braun and S. Takamatsu. Schlechtendalia 4:1, 2000. (3) H. D. Shin and Y. J. La. Mycotaxon 46:445, 1993.

Adverse effects of intraportal chemotherapy on natural killer cell activity in colorectal cancer patients.

BACKGROUND: Adjuvant intraportal chemotherapy has been used with a view to prevent the development of metachronous hepatic metastases following curative resection for colorectal cancer. To evaluate the effects of this therapy on systemic antitumor immunological activity, 35 colorectal cancer patients who underwent curative resection were investigated. METHOD: Among them. 19 had adjuvant intraportal chemotherapy with mitomycin C and 5-fluorouracil (treated group) and 16 had no chemotherapy (untreated group). Natural killer (NK) cell activity, lymphocyte subpopulations, and immunosuppressive acidic protein (IAP) in the peripheral blood were measured serially before and after operation, and the values were compared between the two groups. RESULTS: The NK cell activity and the percentages of CD16 positive and CD56 positive cells were markedly reduced in the treated group postoperatively. Significant difference was also observed between the two groups on the 4th postoperative day in regard to NK cell activity and CD56 positive cells. CONCLUSIONS: Intraportal chemotherapy in our study reduced the NK cell activity and its population in the peripheral blood.

[Treatment of liver metastases from gastric cancer].

Nine patients with liver metastases from gastric cancer were treated in our department since 1986. Hepatectomy was performed in 3 cases and hepatic arterial infusion chemotherapy was performed in 6 cases. In 3 patients in whom hepatectomy was performed, the extent of liver metastases showed 2 H1 and 1 H2. One has survived for 20 months, but the other 2 died after 5 and 7 months, respectively. In 6 patients in whom hepatic arterial infusion chemotherapy was performed, the extent of liver metastases was H3. These patients were treated with 5-FU.EPIR.MMC (3 cases), CDDP.MMC (1 case), MMC only (1 case) and 5-FU.ADM.MMC.CDDP (1 case). This treatment revealed a 50% response rate (CR 1, PR 2). The patient with CR has survived for 6 years and 2 patients with PR died after 8 and 12 months. The patient with CR showed high AFP level (55, 480 ng/ml), and 2 patients with PR showed high AFP level (24, 327 ng/ml) or high CEA level (3,903 ng/ml). The prognosis of hepatectomy for liver metastases from gastric cancer was not so good. Hepatic arterial infusion chemotherapy seemed to be a useful treatment for liver metastases from gastric cancer.

[Long-term follow-up study of I-131 therapy for Graves' disease--index associated with late-onset hypothyroidism].

We have studied the follow-up of thyroid function in the patients with late-onset hypothyroidism and euthyroidism after I-131 therapy of hyperthyroidism. Thirty three patients who did not need the thyroid treatment until ten years after I-131 therapy were classified as euthyroid group. And eleven patients who needed the thyroid supplement of thyroid hormone for late-onset hypothyroidism were classified as hypothyroid group. Patients in both groups who required only a single dose of I-131 for successful treatment of hyperthyroidism had similar age, gland size, 24 hour I-131 uptake, pretreatment serum T3 uptake level and T4 concentration, and I-131 treatment dose. Subclinical hypothyroidism occurred in 28.6% of euthyroid group and 66.7% of hypothyroid group four months after I-131 therapy. The levels of T3 were recovered to higher than normal range at 6 months in euthyroid group, while the levels of T3 were kept within the normal range in the seventy percent of hypothyroid group. Patients who were still lower in the level of T3 uptake than normal range at 6 months had a higher incidence of late-onset hypothyroidism. Our observation showed no significant difference in the course of follow-up studies after I-131 therapy between the patients with late-onset hypothyroidism and euthyroidism.

The sennoside constituents of rhei rhizoma and sennae folium as inhibitors of serum monoamine oxidase.

Four (in total) compounds with inhibitory effects on the activity of bovine serum monoamine oxidase were isolated from the methanol-water extracts of Rhei Rhizoma (Daiou) and Sennae Folium (Senna), and identified as sennosides A, B, E and F. Among them, sennosides A and B were obtained from both Rhei Rhizoma and Sennae Folium, while sennosides E and F were detected only in the former. The 50% inhibitory concentrations of the four sennosides were 17, 9, 24 and 13 microM, respectively, and the type of inhibition by seenosides A and B with respect to allylamine as the substrate was non-competitive.

[Pharmacokinetic analysis in intraperitoneal hyperthermic perfusion using mitomycin C in far-advanced gastric cancer].

Postoperative intraperitoneal hyperthermic perfusion (IPHP) using MMC was performed with marked success on 15 gastric cancer patients with peritoneal dissemination or serosal invasion (first surgery group) and on 5 recurrent gastric cancer patients with ascitic retention (recurrent cancer group), and the MMC concentrations was studied in the perfusate and circulating blood. The perfusate contained MMC 10 micrograms/ml at the onset of IPHP, except one recurrent case of 20 micrograms/ml, and IPHP was performed for 120 minutes except in one case given 20 micrograms/ml of MMC. There was little difference in the hepatorenal functions and perfusate temperatures between the first surgery group and the recurrent cancer group. The drug levels were measured by HPLC method with minimal assay levels of 2 ng/ml. Perfusate drug levels in the first surgery group reduced by half at 12 minutes after the start of IPHP, whereas in the recurrent cancer group, they decreased by half about 60 minutes later. Perfusate drug levels in the first surgery group decreased twice as rapidly as in the recurrent cancer group. The area under the curve (AUC) and average drug levels in the first surgery group were 7,900 micrograms.hr/l and 3.3 micrograms/ml, respectively, and those in the recurrent cancer group were 12,620 micrograms.hr/l and 5.3 micrograms/ml, respectively. On the other hand, the drug levels in peripheral blood were almost the same between the two groups. These data suggest that although recurrent gastric cancer is well suited for IPHP because of high AUC, it is worthwhile performing IPHP combined with surgery for gastric cancer with peritoneal seeding, with due consideration for AUC of 7,900 micrograms.hr/l and the average drug level of 3.3 micrograms/ml.

Clinical trial with surgery and intraperitoneal hyperthermic perfusion for peritoneal recurrence of gastrointestinal cancer.

To treat six patients with peritoneal recurrence after radical operation for gastrointestinal cancer, an intraperitoneal hyperthermic perfusion (IPHP), combined with surgical resection of recurrent tumors, intestinal by-pass anastomosis, or both, was carried out. Immediately after complete resection of the intraperitoneal recurrent tumors, a 2- to 3-hour IPHP was performed under hypothermic general anesthesia at about 32 degrees C, using a perfusate containing 10 micrograms/ml or 20 micrograms/ml of mitomycin C (MMC) warmed at the inflow temperature of 46.6 degrees C to 46.9 degrees C. The apparatus used for IPHP was designed for intraperitoneal perfusion as a closed circuit. Although five of the six patients had a malignant peritoneal effusion at the time of admission, the effusion disappeared soon after IPHP, and no cancer cell was present in the lavage from Douglas' pouch. The other patient had a recurrent tumor at the anastomotic region after low anterior resection for rectal cancer and complete resection of the recurrent tumor, combined with IPHP, was carried out. One patient with a recurrent gastric cancer died of hepatic metastasis and cancerous pleuritis 5 months after this treatment, and the other five are in good health 12.8 +/- 5.1 months after IPHP. On the other hand, five patients with intra-abdominal recurrent gastric cancer, who received only surgical treatment within the same period of time, died 3.0 +/- 2.1 months after the surgery. Postoperatively, in the six patients with IPHP, transitory hepatic dysfunction, hypoproteinemia, and thrombocytopenia occurred. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence of gastrointestinal cancer.

Combined treatment with surgery and intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastrointestinal cancer with peritoneal seeding.

In 19 patients with advanced gastric carcinoma intraperitoneal hyperthermia combined with mitomycin C was administered. After this therapy in repeated cytological examinations of the peritoneal effusion malignant cells could be determined. From 19 patients 5 died innert the first 10 months. The other patients lived 12 months without recurrence.

[The relationship between thermotolerance and the tissue oxygen tension in human gastric cancer tissue].

To study the relationship between thermotolerance and post-thermal phenomenon, tumor pO2 (TpO2) in xenoplanted gastric cancer tissue (H-23) has been measured by a polarographic method. The heat treatment was done in a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. In order to produce thermotolerance, the second treatment was carried out at an interval of 24 hours, or, alternatively at 72 hours, or at 5 days or at 7 days. The thermotolerance of the H-23 tumor reached its maximum at the 72 hour-interval and was seen to disappear completely at 7 days. The TpO2 in the H-23 tumor decreased immediately after a single heat treatment and returned to its pre-treated value after 10 hours. In cases of the second heat treatment, the 72-hour interval group returned to its pre-treated value in 2-6 hours, whereas the 24-hour, 5-day, and 7-day interval groups showed a longer recovery time. The relationship between thermotolerance and TpO2 recovery was inverse at r = -0.858 and p = 0.035. Thus, our study suggests that not only is the thermotolerance affected by the alteration of the intra-cellular components, but also by the post-thermal changes in the tumor vessels.

Enhanced antitumor efficacy with a combination of hyperthermochemotherapy and thermosensitization with polyamine antimetabolites in nude mice.

In an attempt to enhance the antitumor effects of hyperthermochemotherapy, methylglyoxal-bis-guanylhydrazone (MGBG) and alpha-difluoromethylornithine (DFMO) were used in combination with hyperthermochemotherapy of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a (ACNU) against human gastric cancer (ST-2) xenotransplanted into nude mice. After priming with DFMO and MGBG, ACNU was given ip and subsequently, a 23 minute-hyperthermia was carried out by placing the leg with the tumor into a water bath of a temperature of 43.5 +/- 0.1 degrees C. The second hyperthermic treatment was given in the same manner after 48 hours. MGBG and DFMO were administered for 4 successive days from the previous day of the first hyperthermia. In mice treated with DFMO plus MGBG, either tumor growth or tumor tripling time was much the same as in the control, while in mice given MGBG, DFMO plus heat, there was a diminution in tumor growth. Hyperthermia together with MGBG, DFMO plus ACNU brought about remarkable antiproliferative effects on ST-2 tumor growth, compared to three regimens with MGBG, DFMO plus heat, MGBG, DFMO plus ACNU, as well as ACNU plus heat. These data suggest that a combination of MGBG with DFMO leads to a favorable thermosensitization to the antitumor efficacy of ACNU.