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PubMed1997

Hepatic arterial resistance index--an indicator of diffuse liver disease in children treated with bone marrow transplantation.

AIM: To describe the relationship between the resistance index of the common hepatic artery and liver function tests in children undergoing bone marrow transplantation. MATERIALS AND METHODS: We analysed prospectively the results of 106 Doppler ultrasound examinations of the common hepatic artery from 31 bone marrow transplant patients, 16 of whom had normal liver function. The aetiology of the liver dysfunction in the other 15 patients was veno-occlusive disease (n = 7), unknown (n = 3), hepatic graft-versus-host disease (n = 2), hepatitis (n = 2), or cholestasis (n = 1). We assessed the relationships between the hepatic arterial resistance index (HART) and the results of the serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALK), lactate dehydrogenase (LDH) and serum albumin (ALB) assays and calculated HARI break-point values that might distinguish patients with liver disease from patients with the normal liver function. RESULTS: The significant break point (P < 0.05) of the HARI was 0.55 for SGOT, SGPT and ALK. LDH was associated with a break point of 0.53. Resistance indices for the common hepatic artery below the break-point values predicted liver dysfunction with specificities of 81%, 80%, 92% and 93%, respectively. There was no significant relationship between liver function tests and ALB levels. CONCLUSION: If below 0.55, the hepatic arterial resistance index is a non-invasive indicator of liver dysfunction in children undergoing bone marrow transplantation.

Adolescent↗
PubMed2002

[Relationship between acute phase reactant proteins (APRP) and fatigue during post-operative convalescence].

Surgery originates an inflammatory state which triggers an acute phase response (APR). In this study, variations in the acute phase reactant proteins (APRP) and their relationship with fatigue were assessed. A total of 58 candidate patients for elective abdominal surgery participated in this study. In the preoperative period (PRE) and in the post-operative period (9 days [9-P], 27 days [27-P] and 45 days [45-P]), variations in serum APRP and fatigue were analyzed. In the post-operative period (9-P), a significant decrease in PT, ALB, PAB, TRF, and an increase in CER were observed. In 27-P, significant decreases were observed in PAB and PBR, with increased PT and CER, and without significant variations in ALB ad TRF. In the 45-P day, a concomitant increase in PT and CER was observed. Dynamometric parameters also decreased significantly in the post-operative period (9-P). In conclusion, our results demonstrate the existence of changes in serum proteins and in APRP after an elective abdominal surgical intervention, which are associated with fatigue, evaluated both by subjective and objective (dynamometry) means and the use of a mathematical model that considers weight, proteins and APRP.

Acute-Phase Proteins↗
PubMed1984

Kinetic analysis of myocardial fatty acid oxidation suggesting an albumin receptor mediated uptake process.

The relationship between extracellular albumin and non-esterified fatty acid (NEFA) concentrations and the rate of fatty acid oxidation was studied. The data were obtained from tests performed on a working rat heart. When NEFA concentration was increased the rate of fatty acid oxidation showed a saturation curve at a constant NEFA/albumin ratio. Keeping constant the albumin concentration, a rise in NEFA concentration resulted in a linear increase of fatty acid oxidation. No correlation, however, was found between fatty acid oxidation and the unbound fraction of fatty acids. These results suggest an albumin receptor mediated NEFA uptake. With this assumption the following rate law of the NEFA uptake was derived: UPT = UPT0 X [FA]/(Km + [ALB] ) where [FA] and [ALB] are the total NEFA- and albumin concentrations, UPT0 and Km are constants. The rates of oxidation computed with this equation show a very good congruence to the values obtained experimentally. The validity of the rate law is confirmed by the fact that it is shown to be in agreement to the results of other investigators.

Animals↗
PubMedDate not supplied

Unilateral block of NMDA receptors in the amygdala prevents predator stress-induced lasting increases in anxiety-like behavior and unconditioned startle--effective hemisphere depends on the behavior.

Lasting increases in anxiety-like behavior (ALB) in the elevated plus-maze are produced by a single 5-min exposure of a rat to a cat. Rats become more anxious in the plus-maze for up to 3 weeks after the exposure. The first study in this series demonstrated that blockade of NMDA receptors in rats with MK-801, AP7, or CPP, given systemically 30 min prior to exposure to a cat prevents the increase in ALB assessed 1 week later in the elevated plus-maze. To localize the site of action of systemic MK-801, MK-801 was injected in the amygdala 30 min prior to predator stress. Injections were given either unilaterally in either hemisphere, or bilaterally in both hemispheres. The target of the injection was the basolateral amygdala. The effects of injection depended on both the type of behavior and the hemisphere of injection. Injections of MK-801 in a variety of sites in the basolateral amygdala had no effect on the suppression of open-arm exploration produced by predator stress. Other amygdala nuclei or other limbic sites likely mediate the effects of systemically administered MK-801 on this behavior. In contrast, NMDA receptors in the left lateral amygdala mediate lasting suppression of risk assessment. MK-801, in a variety of sites in the left but not right lateral amygdala, blocked the effects of predator stress on risk assessment. This is clear evidence of separability of neural mechanisms controlling open-arm exploration and risk assessment. Different NMDA-dependent amygdala circuitry mediated effects of predator stress on unconditioned acoustic startle 1 week after cat exposure. The data indicate that integrity of the left lateral amygdala is necessary for potentiation of startle amplitude by predator stress, though NMDA receptors are not involved in this function. Nevertheless, NMDA receptors in the right, but not the left lateral amygdala, mediate initiation of changes in startle. The data also suggest that the right amygdala action is "downstream" from the left amygdala contribution. These findings are consistent with the view that NMDA receptors are involved in initiation, but not maintenance, of neural changes mediating lasting increases in anxiety following severe stress. Finally, the findings of the importance of the right amygdala in stress-induced enhancement of the startle response provides neurobiological face validity to predator stress as a model of aspects of posttraumatic stress disorder.

Amygdala↗
PubMed2004

Impact of two annual single-dose mass drug administrations with diethylcarbamazine alone or in combination with albendazole on Wuchereria bancrofti microfilaraemia and antigenaemia in south India.

A two-arm community-based lymphatic filariasis elimination trial is being carried out in Tamil Nadu state, India to assess the effect of 2 annual single-dose mass drug administrations of diethylcarbamazine + albendazole (DEC + ALB) on microfilaraemia and antigenaemia in one arm, and diethylcarbamazine(DEC) alone in the other arm. In a cross-sectional survey at each time-point, 450-650 subjects in childhood (2-9 years old) and young adulthood (10-25 years old) were screened from each treatment arm. After 2 annual mass drug administrations, microfilaraemia prevalence in the 2-drug arm was reduced by 54% and 62% in the 2-9 year old and 10-25 year old groups respectively; and corresponding figures for the single-drug arm were 26% and 37%. Though higher reductions were recorded for geometric mean intensity of microfilaraemia in the 2-9 year old groups for both treatment arms, reduction was more pronounced in the 2-drug arm than the single drug arm (74% vs. 24%) in the 10-25 year old group. The reduction in the antigenaemia prevalence in the 2-9 year old group was evident in both treatment arms, but in the 10-25 year old group the reduction was only 16.8% in the 2-drug arm. Our results suggest that the annual, single-dose combination (DEC + ALB) mass treatment regimen has an enhanced effect against bancroftian filariasis compared to single-drug therapy.

Adolescent↗
PubMedDate not supplied

Efficacy of single dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 micrograms/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micrograms/kg over a period of 15 months after treatment. All but one subject, with 67 microfilariae (mf)/mL, had pre-treatment counts > 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69%) were amicrofilaraemic by membrane filtration 15 months after treatment compared to one of 12 (8%), 3 of 11 (27%), and 3 of 10 (30%) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77% 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of microfilaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasis.

Adolescent↗
PubMed2000

Neuroplasticity in specific limbic system circuits may mediate specific kindling induced changes in animal affect-implications for understanding anxiety associated with epilepsy.

In two complementary experiments, we studied the effects of low frequency stimulation (LFS) of the amygdala on behavioral effects of kindling in rats and cats. These studies tested the hypothesis that kindling induced long term potentiation (KLTP) in amygdala circuits underlies interictal behavioral change. Since LFS can depotentiate LTP, it was predicted that LFS should both depotentiate KLTP and reverse behavioral effects of kindling. In cats, the effects of LFS on KLTP of amygdala efferents was studied, and related to behavioral effects. Partial ventral hippocampal kindling in cats and right amygdala kindling in rodents lastingly increased defensive response to rats in cats, and anxiety-like behavior (ALB) in the elevated plus-maze in rats. In addition, partial kindling reduced predatory attack behavior in cats independent of its effects on defensive response. Partial kindling also induced KLTP of amygdala efferent transmission to ventromedial hypothalamus (VMH) and periaqueductal gray (PAG) in left and right hemispheres. Depotentiation of amygdala efferent KLTP by bilateral amygdala LFS selectively reduced KLTP in right amygdala efferents. At the same time, defensive behavior, but not attack behavior, was returned to levels seen prior to partial kindling. Defensiveness returned to post kindling levels between 44 and 76days after LFS. At the same time, LTP was restored in the right Amygdalo-PAG pathway only. These findings suggest that lasting change in affect produced by kindling depends on LTP of right amygdala efferent transmission to PAG, replicating studies of the effects of FG-7142 on brain and behavior in the cat. The findings suggest further that the spectrum of behavioral changes produced by partial kindling are dependent on changes in a variety of neural circuits, and that amygdala efferent transmission changes are responsible for changes in defensive behavior, but not attack behavior. Effects of LFS were not due to damage, as thresholds to evoke amygdala efferent response were unchanged. Other data suggest KLTP and depotentiation in right Amygdalo-PAG may reflect changes in glutamate receptor density/synapse number. Kindling effects on rat ALB persisted for at least 1month. Bilateral but not unilateral amygdala LFS reversed the effects of kindling on risk assessment in the plus maze for at least 3weeks. Bilateral LFS also reversed the effects of kindling on open arm exploration, but effects were shorter lived, appearing at 1day but not 3weeks after kindling and LFS. These findings are consistent with other studies which suggest that amygdala neuroplasticity in separable amygdala circuits mediates lasting changes in open arm avoidance and risk assessment. Taken together, the findings of both studies support the hypothesis that a form of LTP of specific amygdala circuits underlies lasting changes in affect produced by limbic kindling. Clinical implications of these findings are discussed.

Aggression↗
PubMed2000

Matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF): elevated levels are primarily related to CSF cell count.

Matrix metalloproteinase-9 (MMP-9) was investigated by enzyme-linked immunosorbent assay (ELISA) and zymography in 111 paired CSF and serum samples from patients with various neurological disorders. In 20 patients with blood-brain barrier (BBB) impairment but normal CSF cell count, elevated levels of MMP-9 were not observed by ELISA measurement. Another 11 patients characterized in the same way, exhibited only slightly increased MMP-9 levels. In contrast, in 12 patients with intact BBB but elevated CSF cell count, MMP-9 was increased too. It was shown by the more sensitive zymography that MMP-9 increased if CSF cell count exceeded five cells per microl. Spearman rank statistics revealed that MMP-9 concentration in CSF correlated with CSF cell count (r=0.755; P<0.0001), but not with CSF/serum albumin ratio (Q(Alb)) (r=0.212; P=0.057), a measure for BBB impairment. Moreover, the CSF/serum MMP-9 ratio (Q(MMP-9)) did not correlate with Q(Alb)(r=0.192; P=0.100). By use of a Boyden chamber, in which granulocytes migrated through a reconstituted basement membrane, it was demonstrated that the MMP-9 concentration in the lower chamber correlated very significantly with the number of accumulated cells (r(2)=0.7692; P<0.0001). The meaning of the increase of MMP-9 in CSF is critically discussed.

Adolescent↗
PubMed1998

Induction of a subgroup of acute phase protein genes in mouse liver by hyperthermia.

We have demonstrated that two members of the acute phase reactant family of positively regulated genes, alpha 1-acid glycoprotein (AGP-1 and AGP-2) and C-reactive protein (CRP) are induced by hyperthermia, while two others, the serum amyloid A (SAA) and alpha 1-antitrypsin (AT) genes, are not. Albumin (ALB), a negative acute phase reactant gene, is also induced by hyperthermia. The AGP-1, AGP-2, and CRP genes require glucocorticoids, but not IL-6, IL-1 beta or TNF alpha in response to hyperthermia. As with LPS, the C/EBP beta mRNA levels increased, while the C/EBP alpha mRNA levels decreased in response to LPS. In contrast to the LPS response, C/EBP delta was unchanged. Protein pool levels and DNA-binding activities of the 35 and 20 kDa C/EBP beta isoforms increase, whereas protein pool levels of the 42 kDa C/EBP alpha decrease and the 30kDa remained high. These studies suggest that the synthesis of specific C/EBP alpha and C/EBP beta isoforms is induced by hyperthermia, and that the regulation of the AGP-1 and AGP-2 genes during heat stress may involve one of these isoforms. The difference between the responses to hyperthermia and LPS is that the former, may not involve the participation of cytokines. Furthermore, since cis-acting heat shock elements (HSE) are located in the promoter regions of the ALB, CRP, and C/EBP beta genes, these regulatory sequences may be involved in the in vivo activation of these genes by hyperthermia.

Acute-Phase Proteins↗
PubMed1985

[Anthropometric and biological evaluation of 44 patients with protein-calorie malnutrition].

In industrial countries protein-calorie malnutrition (PCM) is a frequent cause of hospital morbidity and mortality. In this study, 88 hospital patients were evaluated: 44 (25 men and 19 women) aged from 20 to 80 years) with PCM, and 44 without malnutrition; the two groups were matched with regard to sex, age and height. The following parameters were determined: arm muscle surface, whole-body muscle mass, proportion of body fat, serum albumin (Alb), prealbumin (PA), retinol-binding protein (RBP), transferrin, thyroxine-binding protein, thyroxine, triiodothyronine, reverse triiodothyronine and total complement. Anthropometric measurements were validated by planimetry of a computerized tomographic section of the arm in 60 patients. There were significant differences between the two sexes in anthropometric values. Alb, PA and RBP values were different in men and RBP only in women; all other biochemical parameters were the same in both sexes. Thus, the group with PCM could be distinguished from the control group by anthropometric values and RBP values. Anthropometric parameters have been reported as being more specific of PCM than biochemical parameters, but since the latter are considered more sensitive, both complement each other and must be taken into account.

Adult↗
PubMed1998

The effects of intrahippocampal scopolamine infusions on anxiety in rats as measured by the black-white box test.

Hippocampal cholinergic projections mediate attention to arousing stimuli as demonstrated by behavioral, electrophysiological, and endocrine studies. We recently reported that peripheral injections of the cholinergic antagonist scopolamine (SCOP) increased anxiety-like behaviour (ALB) in rats and we sought to investigate if this response might be hippocampally mediated. Adult male, Lister Hooded rats were implanted bilaterally with hippocampal cannulae 3 weeks prior to testing. On the test day, rats were injected with vehicle (VEH; artificial CSF at 3 microl), 15 or 30 microg SCOP, 20 min prior to being placed into the white chamber of the black-white box (n = 10/group). Rats were scored for latencies to exit and reenter the white chamber, total time spent in the white chamber, intercompartmental crossings, and activity. SCOP at 30 microg significantly reduced time to exit the white arena, while both doses of SCOP elevated latencies to reenter the white chamber. There were no effects of SCOP on intercompartmental crossing, time spent in the white chamber, or on activity levels. Loss of hippocampal cholinergic function impairs processing of threatening stimuli that manifests itself as increased ALB.

Analysis of Variance↗
PubMed2002

The effect of Nigella sativa oil against the liver damage induced by Schistosoma mansoni infection in mice.

It has been reported that Nigella sativa oil possesses anticestode and antinematode actions. Besides, it produced a hepatoprotective effect in some models of liver toxicity. Therefore, our aim in this work was to study the effect of the Nigella oil (N.O) on Schistosomiasis mansoni infected mice. The oil was given in two dose levels (2.5 and 5 ml/kg, orally for two weeks) either alone or in combination with praziquantel (PZQ), the drug of choice for the treatment of schistosomiasis. Three aspects of drug action were investigated, the effect on Schistosomiasis mansoni infection, the effect on liver functions, and on redox state. The parasitological investigation included worm distribution, oogram pattern and ova count. Furthermore, liver granuloma diameters were measured. The biochemical parameters were the serum level of L-alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), albumin (Alb) and total protein. Moreover, to assess the antioxidant capability of the Nigella oil, four parameters were studied, viz., liver lipid peroxide (LPD) and reduced glutathione (GSH) contents and the activity of the defence enzyme superoxide dismutase (SOD) and lactate dehydrogenase (LDH). When the oil was given alone, it reduced the number of S. mansoni worms in the liver and decreased the total number of ova deposited in both the liver and the intestine. Furthermore, it increased the number of dead ova in the intestinal wall and reduced the granuloma diameters markedly. When N.O was administered in combination with PZQ, the most prominent effect was a further lowering in the dead ova number over that produced by PZQ alone. Concerning the biochemical parameters, infection of mice with S. mansoni produced a pronounced elevation in the serum activity of ALT, GGT, with a slight increase in AP level. However, it tended to reduce serum albumin level. These changes were accompanied with an alteration in the liver contents of LPD and GSH along with a significant decline in the activity of the cytosolic SOD and LDH. Administration of Nigella sativa oil succeeded partially to correct the previous changes in ALT, GGT, AP activity, as well as the Alb content in serum. However, it failed in the liver to restore either LPD and GSH content or LDH and SOD activities to normal level. These results suggest that Nigella sativa oil may play a role against the alterations caused by S. mansoni infection, an effect which may be induced partly by improving the immunological host system and to some extent with its antioxidant effect.

Analysis of Variance↗
PubMed2002

Acute liver CCl(4) intoxication causes low HSP70 gene expression and a delayed transition through the cell cycle in aged rats.

Since there is still debate about the ability of the aged liver to regenerate, we compared some aspects of this response in young, adult and old rodents. 2, 6, 12 and 19-month-old rats were intraperitoneally injected with CCl(4) (3mg/kg) or left untreated (CT) and killed either 2h (group A) or 24h (group B) after intoxication. Liver injury was checked histologically and by assaying transaminases. mRNA levels of albumin (Alb), c-fos, c-myc, hepatocyte growth factor (HGF), transforming growth factor (TGF)-alpha and TGF-beta1 were also analyzed. Heat shock protein (HSP)70 gene expression was evaluated, and liver GSH content. Transaminases and histology show more damage in aged rats. Alb mRNA was reduced starting at 12 months in group A and at all ages in group B; c-fos and c-myc mRNAs reached the highest levels in 6-month-old rats and the lowest in those aged 12 and 19 months of group A. In group B, c-fos was detectable only in 6-month animals, but c-myc at all ages. HGF, TGF-alpha and TGF-beta1 mRNAs were up-regulated in treated rats, but to a lesser extent in the aged. HSP70 mRNA, absent in CT, was significantly increased at the age of 6 months, undetectable in the oldest rats in group A; in group B it was only visible in 6-month animals. GSH content was reduced with aging. In conclusion, during aging the liver regenerative machinery is preserved but its activation is reduced and delayed.

Aging↗
PubMed1999

Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing genotoxic effects produced by arsenic trioxide in mice: II. Comparative efficacy of an antibiotic, actinomycin D alone and in combination with either of two microdoses.

OBJECTIVE: To determine whether actinomycin-D (AMD), an antibiotic, alters the reported efficacy of a potentized homoeopathic drug, Arsenicum Album, in reducing genotoxic effects produced in arsenic-trioxide-injected mice. DESIGN: Mice were separately injected with AMD, As2O3, and conjointly with AMD plus As2O3, AMD plus homoeopathic drug, AMD plus As2O3 plus homoepathic drug, and As2O3 plus homoeopathic drug in separate sets. METHODS: Several standard cytogenetical endpoints were assessed at different fixation intervals by adopting conventional techniques. RESULTS: Both Ars Alb-30 and Ars Alb-200 showed protective ability against AMD and As2O3 when injected individually, but this ability was reduced considerably in mice injected with AMD and As2O3 together. AMD itself had genotoxic effects, but also apparently reduced genotoxic effects of arsenic to some extent. CONCLUSION: AMD reduced the protective efficacy of the homoeopathic drug against arsenic. This result suggests a mechanism of action for homoeopathy, as AMD is a known transcription-blocker.

Animals↗
PubMed1998

Relationship between serum phosphorus levels and various outcome measures in adult hemodialysis patients.

OBJECTIVE: To compare three different mean serum phosphorus ranges on outcomes related to the control and treatment of hyperparathyroidism (HPTH), to nutritional status, and to quality of life (QOL) in adult hemodialysis (HD) patients. DESIGN: Patients were grouped based on the mean of five monthly phosphorus levels achieved during the study period. Group 1 included patients whose mean phosphorus levels over the period was <6.0 mg/dL (n = 24); group 2 averaged between 6.0 and 6.9 mg/dL (n = 14); and group 3 averaged >7.0 mg/dL (n = 16). Descriptive comparisons were made between phosphorus groups. PATIENTS: Fifty-four stable, adult HD patients participated voluntarily. MAIN OUTCOME MEASURES: Intact-parathyroid hormone (iPTH), calcium x phosphorus product (Ca x P), and change in iPTH, albumin (alb), total protein (tpro), weight (wt) and body mass index (BMI), and scores on a QOL survey. Baseline physical and lab characteristics. RESULTS: No difference was found between phosphorus levels of <6.0 mg/dL and levels of 6.0 to 6.9 mg/dL in iPTH, Ca x P levels allowing safe calcitriol therapy, nor response to calcitriol treatment. Patients with phosphorus levels >7.0 mg/dL had midstudy iPTH greater than phosphorus levels <6.0 mg/dL. Otherwise the three groups did not differ significantly in iPTH levels. Phosphorus levels 6.0 to 6.9 mg/dL was associated with lowest wt and BMI, but alb and tpro did not differ between the phosphorus groups. Phosphorus levels of >7.0 was associated with highest creatinine levels and youngest age. Subjects in the phosphorus levels of <6.0 mg/dL gp were more likely than the 6.0 to 6.9 mg/dL gp to describe their diet as sufficient and, at baseline, were more likely to relate diet to QOL. CONCLUSION: Comparison of three levels of serum phosphorus on indicators of outcome in the control and treatment of secondary hyperparathyroidism showed no significant difference in outcome between phosphorus levels of <6.0 mg/dL and phosphorus levels 6.0 to 6.9 mg/dL. However, the data suggests that phosphorus levels of >7.0 mg/dL may relate to significantly higher iPTH and unacceptable Ca x P levels. There were no differences between the groups, suggesting less favorable outcome at any of the three phosphorus levels regarding nutritional status or QOL in this small group of stable, adult HD patients.

Adult↗
PubMed2001

Does the control of alanine aminotransferase levels lead to a regression of liver fibrosis in chronic hepatitis C patients?

The aim of this study was to investigate the effect of various medications other than interferon (IFN) on liver fibrosis in chronic hepatitis C (CH-C) patients, and the results were compared with those obtained in CH-C patients without therapy. Fifty CH-C patients (32 men and 18 women; mean age 58.5 years) without previous IFN therapy, who randomly received medicines other than IFN such as Stronger Neo-Minophagen C, Ursodeoxycholic acid and a herbal medicine, Sho-saiko-to (TJ-9) (Group I), and as a control group, 45 CH-C patients (27 men and 18 women; mean age 56.6 years) without therapy (Group II) were examined. All patients had persistent alanine aminotransferase (ALT) elevation more than 6 months before this study and were also subdivided into three subgroups according to different pattern of ALT during the observation period, i.e. (a): persistently ALT<60 IU/l (below about twice the upper limit of normal range); (b): persistently ALT>/=60 IU/l; and (c) other than (a) and (b). All patients were biopsied twice before starting this study and during observation period and the liver fibrosis was compared between them by staging in each case. When the fibrosis stage was the same between two specimens, we determined whether the degree of fibrosis had improved or worsened by computed image analysis. Blood tests for fibrosis marker, serum aminoterminal peptide of type III procollagen (P III P) and liver enzyme such as albumin (Alb) and zinc turbidity test (ZTT) levels, and platelet (Plt) counts were also examined on the two times of liver biopsy. As a result, there were no significant differences in fibrotic improvement rate when assessed by both staging only and staging together with fibrotic ratio, determined by computed image analysis and also in yearly change of P III P (P/Y) and fibrosis (F/Y), the changed rate of Alb, ZTT levels and Plt counts between Group I and Group II, except for P/Y in subgroup (a) which was rather higher in Group I than in Group II. There were also no significant relationship between the changes of histological activity and fibrosis staging in both groups. In conclusion, other medications than IFN could not significantly improve both liver fibrosis and its associated laboratory data irrespective of ALT levels in CH-C patients as compared to the control group during average 3 years' follow-up period.

Journal Article↗
PubMed2002

Long-term prognosis of primary biliary cirrhosis (PBC) in Japan and analysis of the factors of stage progression in asymptomatic PBC (a-PBC).

Objective: Based on data from a national survey of primary biliary cirrhosis (PBC), the pathology and prognosis of PBC in Japan were clarified. In particular, we tried to perform multivariate analysis of factors useful in determining prognosis of asymptomatic PBC (a-PBC). Methods: The survey was performed 10 times. Responses from 3778 of 4361 registered patients (416 institutions) were investigated (survey period: January 1968-December 1998). At the time of diagnosis, patients were classified as a-PBC or symptomatic PBC (s1-PBC; pruritus only, s2-PBC; jaundice and serum bilirubin level above 2 mg/dl). The survival rate was obtained by the Kaplan-Meier method. Logistic regression analysis was used in multivariate analysis of prognostic factors of a-PBC. Results: There were no significant differences in clinical findings from those in previous reports. The 5-year survival rates of patients with a-PBC, s1-PBC, and s2-PBC at the time of diagnosis were 97, 88, and 53%, respectively. Patients with a-PBC at the time of diagnosis were divided into groups: those in whom the disease progressed to s2-PBC (8%) and did not progress to s2-PBC (92%) at the final examination, and the prognosis was compared between groups. The prognosis was significantly poorer in the s2-PBC progression group. As a result of multivariate analysis for prediction of prognosis, levels at diagnosis of total serum bilirubin (T-Bil), albumin (Alb), total cholesterol (T-Cho), histological stage, and presence or absence of ursodeoxycholic acid (UDCA) administration were selected as significant factors (P<0.00001). Conclusion: Serum T-Bil, Alb, T-Cho, and histological stage at the time of diagnosis and presence or absence of UDCA administration were considered useful early prognostic indicators in patients diagnosed as having a-PBC whose prognosis may deteriorate with progression to s2-PBC.

Journal Article↗
PubMed1990

Echinococcus granulosus: development of resistance to albendazole in an animal model.

Gerbils with well developed peritoneal cysts of Echinococcus granulosus were randomized to albendazole 50 mg/kg/day or untreated control. Treated animals had less disease at post mortem after 3 months of treatment. Cysts were then taken from both albendazole-treated and control animals and cultured in vitro either with or without albendazole sulphoxide (Alb Sx) 500 micrograms/L for 14 days. Viability of cysts was then established by implantation of whole cysts into gerbils. Whilst naive cysts were affected by Alb Sx (only 2 cysts developed/gerbil) cysts from animals treated with albendazole were not sensitive to further therapy (6.4 cysts/gerbil).

Albendazole↗