Homeopathic Oscillococcinum® for preventing and treating influenza and influenza-like illness.

BACKGROUND: Influenza is a highly infectious viral disease that is particularly common in the winter months. Oscillococcinum® is a patented homeopathic medicine that is made from a 1% solution of wild duck heart and liver extract, which is then serially diluted 200 times with water and alcohol. OBJECTIVES: To determine whether homeopathic Oscillococcinum® is more effective than placebo in the prevention and/or treatment of influenza and influenza-like illness in adults or children. SEARCH METHODS: We searched CENTRAL (2014, Issue 8), MEDLINE (1966 to August week 4, 2014), MEDLINE In-Process & Other Non-Indexed Citations (4 September 2014), AMED (2006 to September 2014), Web of Science (1985 to September 2014), LILACS (1985 to September 2014) and EMBASE (1980 to September 2014). We contacted the manufacturers of Oscillococcinum® for information on further trials. SELECTION CRITERIA: Randomised, placebo-controlled trials of Oscillococcinum® in the prevention and/or treatment of influenza and influenza-like illness in adults or children. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed risk of bias in the eligible trials. MAIN RESULTS: No new trials were included in this 2014 update. We included six studies: two prophylaxis trials (327 young to middle-aged adults in Russia) and four treatment trials (1196 teenagers and adults in France and Germany). The overall standard of trial reporting was poor and hence many important methodological aspects of the trials had unclear risk of bias. There was no statistically significant difference between the effects of Oscillococcinum® and placebo in the prevention of influenza-like illness: risk ratio (RR) 0.48, 95% confidence interval (CI) 0.17 to 1.34, P value = 0.16. Two treatment trials (judged as 'low quality') reported sufficient information to allow full data extraction: 48 hours after commencing treatment, there was an absolute risk reduction of 7.7% in the frequency of symptom relief with Oscillococcinum® compared with that of placebo (risk difference (RD) 0.077, 95% CI 0.03 to 0.12); the RR was 1.86 (95% CI 1.27 to 2.73; P value = 0.001). A significant but lesser effect was observed at three days (RR 1.27, 95% CI 1.03 to 1.56; P value = 0.03), and no significant difference between the groups was noted at four days (RR 1.11, 95% CI 0.98 to 1.27; P value = 0.10) or at five days (RR 1.06, 95% CI 0.96 to 1.16; P value = 0.25). One of the six studies reported one patient who suffered an adverse effect (headache) from taking Oscillococcinum®. AUTHORS' CONCLUSIONS: There is insufficient good evidence to enable robust conclusions to be made about Oscillococcinum® in the prevention or treatment of influenza and influenza-like illness. Our findings do not rule out the possibility that Oscillococcinum® could have a clinically useful treatment effect but, given the low quality of the eligible studies, the evidence is not compelling. There was no evidence of clinically important harms due to Oscillococcinum®.

Efficacy and safety of human placental extract for alcoholic and nonalcoholic steatohepatitis: an open-label, randomized, comparative study.

Human placental extract (HPE) is a traditional medicine that has been used for the symptomatic treatment of liver disease without any verifying clinical evidence. This study aimed to evaluate the efficacy and safety of HPE in patients with alcoholic or nonalcoholic steatohepatitis (ASH or NASH). We designed this clinical trial as a multicenter, open-label, randomized, comparative noninferiority study to improve the reliability of analyses. The enrollment criteria were limited to ASH or NASH patients with serum alanine aminotransferase (ALT) 1.5-fold higher than the normal level. Patients in the control group were treated with a commercially available mixture of liver extract and flavin adenine dinucleotide (LE­FAD). Intention-to-treat (ITT) analysis was applied to 194 patients, and per-protocol (PP) analysis was available for 154 patients. The rate of primary goal achievement of treatment efficacy was arbitrarily defined as 20% or greater improvement in ALT level compared with the pretreatment level and did not differ significantly between the HPE and control groups [62.9% (44/70) vs. 48.8% (41/84); p=0.0772]. ITT and modified ITT analysis showed results similar to those of PP analysis. Adverse drug reactions (ADRs) of minimal to moderate degree occurred in 3.1% of patients. The ADR and treatment compliance rates were similar in both groups. In conclusion, the clinical value of HPE in the treatment of ASH and NASH is equivalent to that of LE­FAD.

Liver hydrolysate assists in the recovery from physical fatigue in a mouse model.

It is reported that liver hydrolysate (LH) enhances liver function. However, the effects of LH on physical fatigue are unknown. The aim of this study was to investigate the effect of LH on alterations in locomotor activity and energy metabolism such as 5'-AMP-activated protein kinase (AMPK), glycogen content, and blood lactic acid, after forced walking. Adult male ddY mice were used. Locomotor activity, AMPK phosphorylation, and glycogen content in the liver and soleus muscle, as well as blood lactic acid were determined following LH treatment before and/or after forced walking. The locomotor activity significantly decreased after forced walking for 3 h. Two administrations of LH (30 or 100 mg/kg) significantly increased the locomotor activity, while a single administration either before or after forced walking did not show any specific effect. Administering LH twice activated AMPK in the liver and soleus muscle. Glycogen levels significantly decreased in both the liver and soleus muscle after forced walking, whereas the blood lactate level significantly increased. In contrast, administering LH twice increased muscle glycogen and decreased blood lactic acid. These findings indicate that LH produced an anti-fatigue effect and that this effect appears to involve the efficient glycogen utilization through activation of AMPK.

Homeopathic Oscillococcinum(®) for preventing and treating influenza and influenza-like illness.

BACKGROUND: Influenza is a highly infectious viral disease that is particularly common in the winter months. Oscillococcinum(®) is a patented homeopathic medicine that is made from a 1% solution of wild duck heart and liver extract, which is then serially diluted 200 times with water and alcohol. OBJECTIVES: To determine whether homeopathic Oscillococcinum(®) is more effective than placebo in the prevention and/or treatment of influenza and influenza-like illness in adults or children. SEARCH METHODS: We searched CENTRAL (2012, Issue 7), MEDLINE (1966 to July week 4, 2012), MEDLINE In-Process & Other Non-Indexed Citations (6 August 2012), AMED (2006 to August 2012), Web of Science (1985 to August 2012), LILACS (1985 to August 2012) and EMBASE (1980 to August 2012). We contacted the manufacturers of Oscillococcinum(®) for information of more trials. SELECTION CRITERIA: Randomised, placebo-controlled trials of Oscillococcinum(®) in the prevention and/or treatment of influenza and influenza-like illness in adults or children. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed risk of bias in the eligible trials. MAIN RESULTS: We included six studies: two prophylaxis trials (327 young to middle-aged adults in Russia) and four treatment trials (1196 teenagers and adults in France and Germany). The overall standard of trial reporting was poor and hence many important methodological aspects of the trials had unclear risk of bias. There was no statistically significant difference between the effects of Oscillococcinum(®) and placebo in the prevention of influenza-like illness: risk ratio (RR) 0.48, 95% confidence interval (CI) 0.17 to 1.34, P = 0.16. Two treatment trials (judged as 'low quality') reported sufficient information to allow full data extraction: 48 hours after commencing treatment, there was an absolute risk reduction of 7.7% in the frequency of symptom relief with Oscillococcinum(®) compared with that of placebo (risk difference (RD) 0.077; 95% CI 0.03 to 0.12); the RR was 1.86 (95% CI 1.27 to 2.73; P = 0.001). A significant but lesser effect was observed at three days (RR 1.27, 95% CI 1.03 to 1.56; P = 0.03), and no significant difference between the groups was noted at four days (RR 1.11, 95% CI 0.98 to 1.27; P = 0.10) or at five days (RR 1.06; 95% CI 0.96 to 1.16; P = 0.25). One of the six studies reported one patient who suffered an adverse effect (headache) from taking Oscillococcinum(®). AUTHORS' CONCLUSIONS: There is insufficient good evidence to enable robust conclusions to be made about Oscillococcinum(®) in the prevention or treatment of influenza and influenza-like illness. Our findings do not rule out the possibility that Oscillococcinum(®) could have a clinically useful treatment effect but, given the low quality of the eligible studies, the evidence is not compelling. There was no evidence of clinically important harms due to Oscillococcinum(®).

Study on the antidiabetic mechanism of a shark liver peptide, S-8300, in alloxan-induced diabetes.

OBJECTIVES: The aim was to evaluate the antidiabetic mechanism of S-8300 in alloxan-diabetic mice. METHODS: Diabetes was induced by a single intravenous injection of alloxan (60 mg/kg). The effects of S-8300 on diabetic mice were investigated by observing the change in fasting plasma glucose, detecting Fas mRNA by reverse transcriptase-polymerase chain reaction, Fas protein expression in the pancreas by immunohistochemistry and Western blot, and the DNA fragmentation pattern forming a ladder by electrophoresis. KEY FINDINGS: A significant decrease in fasting plasma glucose was observed, and Fas mRNA and Fas protein expression in the pancreas were attenuated in diabetic mice treated with S-8300. Treatment with S-8300 also attenuated DNA ladder formation. CONCLUSIONS: The results suggest that S-8300 inhibits Fas protein-mediated apoptosis of pancreas cells.

[A multicenter clinical study of nafate for treatment of hepatic fibrosis in patients with chronic liver diseases].

OBJECTIVES: To investigate the effect of nafate (compound fetal cow liver extract tablets) in hepatic fibrosis patients with chronic liver diseases. METHODS: One hundred fifteen hepatic fibrosis patients with chronic liver diseases from 3 medical centers were included in this study. All patients were given nafate orally for twenty-four weeks. Before treatment and 12, 24 and 36 weeks after the treatment, serum levels of hyaluronic acid (HA), laminin (LN) and type IV collagen (IV-C) of the patients were measured by radioimmunoassay and their liver biopsy specimens were also assessed. RESULTS: Before treatment and 24 and 36 weeks after the nafate treatment, serum levels of HA were (279.2+/-81.4) ng/ml, (136.8+/-56.7) ng/ml and (86.9+/-40.7) ng/ml respectively, serum levels of LN were (170.8+/-73.0) ng/ml, (112.5+/-39.5) ng/ml, and (60.8+/-31.8) ng/ml respectively, and IV-C levels were (153.7+/-60.1) ng/ml, (112.4+/-43.1) ng/ml, and (96.3+/-44.1) ng/ml respectively. There was a significant reduction in these serum values after the treatments. Histopathological examinations of the liver biopsies showed that the degree of hepatic fibrosis obviously declined by one or two degrees after the treatments. CONCLUSIONS: nafate has positive effects in treating hepatic fibrosis.

Activity of nucleolar organizers in hepatocytes of rats with cirrhosis of the liver after treatment with bioactive preparations.

The therapeutic efficiency of bioactive preparations of the liver and spleen in the treatment of experimental toxic cirrhosis of the liver is shown. Evaluation of the nucleolar organizer activity showed the highest efficiency of treatment with human fetal liver extract.

Antidiabetic effect of a new peptide from Squalus mitsukurii liver (S-8300) in alloxan-diabetes.

1. The purpose of the present study was to evaluate the antidiabetic effect of S-8300 in alloxan diabetic mice. 2. Diabetes was induced by single intravenous injection of alloxan (60 mg/kg bodyweight). 3. The effects of S-8300 on diabetic mice were investigated by observing changes in the glycometabolic index (fasting plasma glucose, glycosylated haemoglobin), the lipometabolic index (triglyceride, cholesterol, free fatty acids), anti-oxidant index (superoxide dismutase, malondialdehyde) and in the degree of injury of beta-cells in the pancreatic islets. 4. A significant decrease in fasting plasma glucose, glycosylated haemoglobin, triglycerides, cholesterol, free fatty acids in the plasma and malondialdehyde in the tissues, as well as a significant increase in the activity of superoxide dismutase, was observed in diabetic mice treated with 10, 3 and 1 mg/kg S-8300. 5. Treatment with S-8300 also attenuated the degree of injury of beta-cells. 6. A comparison was made between the action of S-8300 and 6 U/kg insulin. The effects of S-8300 were similar to those of insulin.

Additive therapeutic effects of the liver extract preparation mixture adelavin-9 on interferon-beta treatment for chronic hepatitis C.

BACKGROUND/AIMS: We previously reported that intravenous interferon-beta administration was effective in treating patients with chronic hepatitis C and that there was no significant correlation between the response to therapy and host in vitro immunoglobulin production. The aims of this study were to evaluate the additive effect of a liver extract preparation and flavin adenine dinucleotide mixture and to reevaluate the correlation. METHODOLOGY: 65 patients with chronic hepatitis C received intravenously 6 million units of interferon-beta and 2 mL of a liver extract preparation and flavin adenine dinucleotide mixture. The results of this study were compared with those of our previous study, on interferon-beta monotherapy in 91 patients with chronic hepatitis C. In addition, peripheral blood mononuclear cells were obtained before interferon-beta administration and cultured. Immunoglobulin concentrations in their supernatants were measured and the correlation with the interferon response was evaluated. RESULTS: The virological end-of-treatment or sustained response occurred in 49 of 58 cases (84.5%), and 16 of 58 cases (27.6%), respectively. Biochemical end-of-treatment or sustained responses occurred in 22 of 58 cases (37.9%), and 30 of 58 cases (51.7%), respectively. These response rates were higher than those reported in our previous study of interferon monotherapy. Monovariate analysis indicated that the use of the liver extract preparation and flavin adenine dinucleotide mixture was a significant predictor of the virological end-of-treatment response and the sustained biochemical response, but by multivariate analysis these relationships were not significant. Immunoglobulin production was not correlated with the virological and biochemical responses. CONCLUSIONS: This study indicated that combination therapy with intravenous interferon-beta and the liver extract preparation and flavin adenine dinucleotide mixture was more effective than intravenous interferon-beta monotherapy. However, no correlation between the interferon response and in vitro immunoglobulin production was observed.

Effect of the single major proteic fractions of the liver perchloric extract UK101 on the development of oral tumours in Syrian hamsters.

Squamous cell carcinoma of the oral cavity continues to be a major clinical problem, with about 100,000 new deaths each year worldwide. There is therefore a need to search for new tools to aid oral cancer treatment. We tested the inhibitory activity on chemical carcinogenesis of the three principal protein fractions of about 50, 14, and 8.5 kDa of the mixture UK101 derived from goat liver. These are composed principally of a glycoprotein rich in mannose residues, a protein with analogy to the heat shock protein family, and ubiquitin, respectively. The animal model employed was dimethylbenzanthracene-induced hamster cheek pouch carcinoma. Number of tumours per animal, tumour mass per animal, and proliferating cell nuclear antigen (PCNA) in non-tumour mucosa were quantified: the 14-kDa fraction was the most active; this was also confirmed by testing its corresponding recombinant material. The 50-kDa fraction was inactive, while the ubiquitin showed only low inhibitory activity. It is possible that the technique described and the results obtained could lead to an interesting clinical approach to the treatment of oral cancer.

Potential in vitro activity of Kutapressin against Epstein-Barr virus.

BACKGROUND: Kutapressin (KU), a porcine liver extract with bradykinin-potentiating effects but no vitamin B 12 activity, has been used in the treatment of Herpes zoster. We examined a phenol-free preparation of this drug for in vitro activity against Epstein-Barr Virus (EBV). MATERIALS AND METHODS: Immortalization-inhibition assays were used to assess EBV infectivity. Mitogen stimulation and cell viability assays were used to assess kutapression toxicity. Lytic replication assays and flow cytometry were used to assess the mechanism of drug activity. RESULTS: Seventy-five hundred mcg/ml of KU blocked the infection of 2 x 10(5) human umbilical cord mononuclear cells when added together with two strains of EBV (B95-8 and FF41). Doses as low as 250 mcg/ml were occasionally effective as well. Unlike acyclovir, KU does not inhibit viral DNA polymerase nor does it appear to compete with EBV as it binds to its receptor on the B-cell surface. CONCLUSIONS: The mechanism whereby KU may inhibit EBV immortalization remains to be determined. KU, a drug which is safe in humans, deserves further study as an agent with potential to block EBV-induced immortalization of B-lymphocytes.

Enhancing effect of the liver extract and flavin adenin dinucleotide mixture on anti-viral efficacy of interferon in patients with chronic hepatitis C.

A combined preparation of liver extract and flavin adenin dinucleotide (FAD) (Adelavin) has been widely used in patients with chronic liver diseases in Japan. One milliliter of this agent contains 15 microliters of phenol-soluble phase of liver nucleic acid fraction and 10 mg of FAD. To examine the advantages of using this preparation in the elimination of hepatitis C virus (HCV) from patients with chronic hepatitis (CH)-C receiving interferon (IFN), 2 ml of this preparation was intravenously (n = 9) or intramuscularly (n = 8) administered daily for 5 days before 6 million units of IFN-alpha was intramuscularly injected once. Before and 48 hours after the injection of IFN, serum ALT, 2'5'-oligoadenylate synthetase (2'5-AS) activity, and HCV RNA levels were measured. The daily administration of this preparation alone for 5 days did not significantly change serum ALT, 2'5-AS activities, and HCV RNA levels. The 2'5-AS activities were significantly increased by IFN after the intravenous injection of this preparation (p < 0.01), while an injection of IFN alone of this dose did not change its activities (n = 10). HCV RNA levels were significantly decreased by IFN only after the administration of the preparation (intramuscular, p < 0.01; intravenous, p < 0.01). The effect of intravenous injection of this preparation was also elicited in patients with HCV genotype II and with HCV more than 10(5) copies/ml. These results suggest that this preparation may enhance the 2'5-AS production by IFN as a result of the increase in mitochondrial adenosin triphosphate production and may be a potent agent to enhance the anti-viral efficacy of IFN in patients with CH-C.

A comparative study of isolutrol versus benzoyl peroxide in the treatment of acne.

Isolutrol is the active principle isolated from aqueous tissue extracts of deep sea shark liver and gall-bladder. A previous study has demonstrated the ability of isolutrol to reduce hyperseborrhoea, which provides a rationale for its use in the treatment of acne. We have performed a double-blind clinical trial on 70 patients to evaluate the efficacy and skin tolerance of isolutrol 0.15 g/100 mL (Ketsugo) in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results from this study showed that both isolutrol and benzoyl peroxide significantly improved patients' acne by reducing the number of inflamed lesions. Isolutrol did not significantly reduce the numbers of non-inflamed lesions whereas benzoyl peroxide did. Fewer side effects were experienced by patients treated with isolutrol when compared with benzoyl peroxide. These results indicate that isolutrol may be a useful adjunct in the treatment of acne, particularly in patients with inflamed lesions.

[The efficacy of vitogepat and sirepar in combination with karsil in chronic liver lesions]. / Effektivnost' vitogepata i sirepara v sochetanii s karsilom pri khronicheskom porazhenii pecheni.

It has been shown in experiments on white rats that chronic (for one month) intoxication with CCl4 and C2H5OH results in liver injury. It manifests by activation of aminotransferases (ALT, AST) and alkaline phosphatase in blood serum, initiation of lipid peroxidation, depletion of the liver pool of reduced glutathione, and suppression of bile production. The liver preparations (sirepar and vitohepat) reduce hepatotoxicity of the poisons in question. The use of vitohepat and sirepar in combination with carsil potentiated hepatoprotective and antioxidative activity of the liver preparations.

[Analysis of the clinical effect of Adelavin infusion during enflurane anesthesia on post-operative hepatic function].

The protective effect of Adelavin, which is made of liver essence, for maintaining postoperative hepatic function was analysed in 85 patients who had enflurane anesthesia. The patients who showed hepatic dysfunction preoperatively were excluded from this trial. Adelavin was infused at a speed of 0.1 mg.kg-1.hr-1 during anesthesia. The group who had upper abdominal surgery in the Adelavin group showed significantly lower incidence of postoperative hepatic dysfunction. The group who had only enflurane anesthesia in the Adelavin group showed significantly lower incidence of postoperative hepatic dysfunction. These results suggest that the Adelavin infusion has a significant protective effect on hepatic function after enflurane anesthesia.

Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome.

Chronic fatigue syndrome is a recently defined entity for which clinical criteria were proposed by the Centers for Disease Control, Atlanta, Ga. A frequently advocated treatment in Southern California is an injectable solution of bovine liver extract containing folic acid and cyanocobalamin (LEFAC). We conducted a double-blind, placebo-controlled, crossover trial of intramuscular LEFAC in 15 patients who met the Centers for Disease Control criteria for chronic fatigue syndrome. Although patients responded to placebo and LEFAC by several criteria of functional status, no significant difference was apparent between response to placebo and that to LEFAC. The placebo response appeared to be strong.