The beneficial impacts of splanchnic vasoactive agents on hepatic functional recovery in massive hepatectomy porcine model

BackgroundExcessive portal pressure after massive hepatectomy can cause hepatic sinusoidal injury and have deleterious impacts on hepatic functional recovery, contributing to developing post-hepatectomy liver failure. This study aimed to assess the effects of splanchnic vasoactive agents on hepatic functional recovery and regeneration while clarifying the underlying mechanism, using a 70% hepatectomy porcine model.MethodsEighteen pigs undergoing 70% hepatectomy were involved in this study and divided into three groups: control (n=6), terlipressin (n=6), and octreotide (n=6). Terlipressin (0.5 mg) and octreotide (0.2 mg) were administered 3 times a day for each group with the first dose starting just before surgery until the 7th postoperative day, at which time the surviving pigs were sacrificed. During the period, portal pressure, liver weight, biochemical analysis, histological injury score, and molecular markers were evaluated and compared between groups.ResultsThe 7-day survival rates in the octreotide, terlipressin, and control groups were 100%, 83.3%, and 66.7%, respectively. The portal pressures decreased in both terlipressin and octreotide groups than the control group at 30 minutes, 1 hour and 6 hours after hepatectomy. The amount of regeneration measured by liver weight to body weight ratio at the time of sacrifice in the terlipressin group was smaller than that in the control group (117% vs. 129%, P=0.03). Serum aspartate aminotransferase (AST) and total bilirubin levels at 1 and 6 hours after hepatectomy and prothrombin time/international normalized ratio (PT/INR) at 6 hours after hepatectomy were significantly improved in the terlipressin and octreotide groups compared to the control group. Serum endothelin-1 (ET-1) was significantly lower in the terlipressin group than that in the control group 6 hours after hepatectomy (P<0.01). The histological injury score in the control group was significantly higher than that in the terlipressin group on the 7th postoperative day (P<0.01).ConclusionsSplanchnic vasoactive agents, such as terlipressin and octreotide, could effectively decrease portal pressure and attenuate liver injury after massive hepatectomy.     

In vitro cellular immune responses to recombinant antigens of Mycobacterium avium subsp. paratuberculosis

Five recombinant antigens (Ags; 85A, 85B, 85C, superoxide dismutase [SOD], and 35-kDa protein) were purified from Mycobacterium avium subsp. paratuberculosis and evaluated for their ability to stimulate peripheral blood mononuclear cells (PMBCs) from fecal-culture-positive cows (low and medium shedders) and culture-negative healthy cows. Recombinant Ags 85A, 85B, and 85C induced significant lymphocyte proliferation as well as the production of gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-12, and tumor necrosis factor alpha (TNF-alpha), but not IL-4, from low and medium shedders. The 85 antigen complex did not stimulate PMBC proliferation from culture-negative healthy cows. The 35-kDa protein also induced significant lymphocyte proliferation as well as the production of IFN-gamma and IL-4 from low and medium shedders. CD4(+) T cells and CD25(+) (IL-2R) T cells were stimulated the most by 85A and 85B, while the 35-kDa protein primarily stimulated CD21(+) B cells involved in humoral immune responses. Interestingly, SOD was less immunostimulatory than other antigens but strongly induced gammadelta(+) T cells, which are thought to be important in the early stages of infection, such as pathogen entry. These data provide important insight into how improved vaccines against mycobacterial infections might be constructed.     

Optic disc and early glaucomatous visual field loss

In the early stages of glaucoma, the disc changes prior to visual field loss, so assessment of the optic disc is very important for the evaluation of the glaucoma patient. The aim of this study is to assess the glaucomatous disc and to look for the features of the optic disc that are commonly associated with early visual field loss. Forty-three eyes of 28 patients were included in this investigation. The criteria for inclusion were a cup/disc(C/D) ratio of more than 0.4 by direct ophthalmoscopy, no visual field defect with Goldmann perimetry, and open anterior chamber angle. Each optic disc was photographed with a Canon fundus camera with Polaroid 600 Plus film. Each photographic set was then examined stereoscopically for morphologic parameters: 1) comparison of vertical versus horizontal C/D ratio; 2) presence of nasal cupping; 3) presence of overpassing vessels; 4) presence of baring of circumlinear vessels; 5) presence of peripapillary atrophy; 6) ratio of the thinnest neuroretinal rim(NRR) width in the vertical sectors of the NRR width of the temporal sector. All subject's central visual fields were examined with an automated static perimeter, Humphrey program C30-2 with STATPAC. The C/D ratio estimated by direct ophthalmoscopy consistently showed a smaller C/D ratio than that found by the stereophotographic method. The parameter with the highest probability value to differentiate between the optic disc of the early visual field loss and the optic disc of normal subjects was "Ratio of the thinnest NRR width in the vertical sectors to the NRR width of the temporal sector less than or equal to 85%". Although it has less resolving power than slide film, a stereo disc photograph with Polaroid film is a quick and simple method of recording changes, and the ratio of the thinnest NRR width in the vertical sectors to the temporal sector is a good predictive parameter for detection of early visual field loss.     

A rubrofusarin gentiobioside isomer from roastedCassia tora

From the roasted seeds ofCassia tora L., a new naphthopyrone glycoside was isolated and characterized as 10-[(β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosyl)oxyl-5-hydroxy-8-methoxy-2-methyl-4H-naphtho [1,2-b]pyran-4-one(isorubrofusarin gentiobioside). Along with isorubrofusarin gentiobioside, alaternin and adenosine were isolated and identified.     

Chlorogenic acid, an antioxidant principle from the aerial parts ofArtemisia iwayomogi that acts on 1,1-diphenyl-2-picrylhydrazyl radical

The antioxidant activity ofArtemisia iwayomogi was determined by measuring the radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical The methanol extract ofA. iwayomogi showed strong antioxidant activity, and thus fractionated with several solvents. The antioxidant activity potential of the individual fraction was in the order of ethyl acetate>n-butanol>water>chloroform>n-hexane fraction. The ethyl acetate andn-butanol soluble fractions exhibiting strong antioxidant activity were further purified by repeated silica gel and Sephadex LH-20 column chromatography. Antioxidant chlorogenic acid was isolated as one of the active principles from then-butanol fraction, together with the inactive components, 1-octacosanol, scopoletin, scopolin, apigenin 7,4′-di-O-methylether luteolin 6,3′-di-O-methylether (jaceosidin), apigenin 7-methylether (genkwanin), 2,4-dihydroxy-6-methoxyacetophenone 4-O-β-D-glucopyranoside and quebrachitol. The antioxidant activity of chlorogenic acid was comparable to that of L-ascorbic acid, which is a well known antioxidant.     

An efficient synthesis of 3-(E)-hydroxypropenyl cephem derivatives, key intermediates for 3-(E)-ammoniopropenylcephalosporin antibiotics

An efficient synthesis of 3-(E)-hydroxy- and 3-(E)-acetoxypropenylcephem derivatives, key intermediates for the synthesis of 3-(E)-propenylcephalosporins was achievedvia Stille coupling reaction of 3-trifloxycephem with 3-(E)-tributylstannylallylic alcohol.     

Estrogen modulation of human breast cancer cell growth

To gain further insight into how estrogens modulate cell function, the effects of estrogen on cell proliferation were studied in human breast cancer cells. We examined the effects of estrogen on the proliferation of three human breast cancer cell lines that differed in their estrogen receptor contents. Ten nM estradiol markedly stimulated the proliferation of MCF-7 human breast cancer cells that contained high levels of estrogen receptor (1.15+/-0.03 pmole/mg protein) over that of control. In T47D cells that contained low levels of estrogen receptor (0.23+/-0.05 pmole/mg protein), Ten nM estrogen slightly stimulated the proliferation over that of control. MDA-MB-231 cells, that contained no detectable levels of estrogen receptors, had their growth unaffected by estrogen. These results showed their sensitivity to growth stimulation by estrogen correlated well with their estrogen receptor content. Also we examined the effect of estrogen on cellular progesterone receptor level as well as plasminogen activator activity in MCF-7 cells. Ten nM estradiol showed maximal stimulation of progesterone receptor level as well as plasminogen activator activity in MCF-7 cells. It is not clear whether these stimulations of progesterone receptor and plasminogen activator activity by estrogen are related to the estrogen stimulation of cell proliferation of MCF-7 cells. Studies with estrogen in human breast cancer cells in culture indicate that sensitivity to growth stimulation by estrogen correlates well with estrogen receptor contents.     

Effect of hepatic cirrhosis on the pharmacokinetics of theophylline in rats

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethylnitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life (t_1/2) in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL (8.67±4.85%) decreased about four-folds, but in DMNA (73.00±9.85%) similar result, was observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.     

Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng

A genuine dammarane-glycoside, named as ginsenoside Rs₃, was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6″-O-acetyl-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.     

Therapeutic horseback riding:

This paper reviews the literature on the benefits of therapeutic horseback riding and the outcomes of eleven data-based studies purpoting to validate the claims that horseback riding offers therapeutic benefits. These studies have focused on physical and psychosocial variables. The literature on the benefits of riding reported obvious beneficial effects, while the outcome studies were able to document only some of these claims. The studies generally reported some significant effects from the therapeutic intervention. An examination of the outcome studies revealed weak scientific rigor, small sample sizes, and a lack of homogeneous populations. Furthermore, use of standardized measures was limited as authors frequently relied on nonstandardized observational techniques to evaluate change. This review indicates a need for further research into both the physical and psychosocial areas with both children and adults. In addition, there is a need for research which would improve the methodological rigor, homogeneity of populations, sample size, and use of standardized measurement instruments.