Evidence that naturopathic therapy including Cordyceps sinensis prolongs survival of patients with hepatocellular carcinoma.

Hypothesis: Naturopathic treatment will benefit patients with hepatocellular carcinoma (HCC).

Study Design: Retrospective analysis of case series of HCC patients treated with naturopathic agents.

Methods: HCC was diagnosed by dynamic computed tomography (CT) imaging and α-fetoprotein (AFP) or PIVKA II, or by histology.

Topical application of the immunosuppressant tacrolimus accelerates carcinogenesis in mouse skin.

Background: Tacrolimus, produced by the fungus Streptomyces tsukabaensis, is a potent macrolide immunosuppressant widely used in liver and kidney transplantation. Topical tacrolimus has recently been found to be an effective treatment for atopic dermatitis (AD).

Objectives: Because of the well-known association between T-cell immunosuppression and an increased risk of carcinogenesis, we investigated the effect of topical tacrolimus on skin carcinogenesis in 117 mice.

Protein oxidative damage in the stratum corneum: Evidence for a link between environmental oxidants and the changing prevalence and nature of atopic dermatitis in Japan.

Background: The incidence of atopic dermatitis (AD) has increased in Japan, along with the number of patients with severe and treatment-resistant AD in urban and industrial areas. We hypothesize that these changes could be due to increased reactive oxygen species (ROS) generated from environmental pollution and solar radiation.

Objectives: To demonstrate whether direct oxidative protein damage of the stratum corneum of the biopsied skin from AD patients is increased when compared with controls.

Plant self-defense mechanisms against oxidative injury and protection of the forest by planting trees of triploids and tetraploids.

The depletion of the ozone layer, and the resulting substantial increase in incident ultraviolet (UV) irradiation and subsequent oxygen radical formation on the Earth, have caused an extensive variety of damage to the world's forests. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px), which scavenge harmful oxygen radicals and inhibit lipid peroxides, were examined in two types of Japanese cedars, black pines, and cypresses, namely those with leaves showing premature withering, shedding, or dying and those with leaves not showing these effects prematurely. The effect of homogenates from these trees on lipid peroxide formation in a reaction system which UV light induces was also studied.

Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer.

The beta-chemokine RANTES was measured in plasma in 43 patients with breast cancer and in 23 patients with cervical cancer, and the RANTES content in primary tumors, tumor metastatic to lymph nodes, and clinically normal skin or pelvic mucosa was measured. In addition, plasma levels were determined in all of the patients for the platelet-derived chemokine beta-thromboglobulin (beta-TG) and for IFN-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-10, along with serum IgE levels and blood eosinophils. Plasma RANTES levels were found to be higher in order of stages IV, III, II, and I of each cancer except for stage I.

Evidence for degradation of cytokines in the serum of patients with atopic dermatitis by calcium-dependent protease.

Changes in the levels of cytokines in the circulating blood and skin have been reported in patients with atopic dermatitis (AD). We determined IFN-gamma, IL-2, IL-4, IL-5 and IL-10 in both the serum and plasma of 45 AD patients and 20 healthy donors. Since differences in the levels of these cytokines between serum and plasma were found, the roles of Ca2+ and proteolytic enzymes were examined.

[Cytokine assessed in the serum are denatured by calcium ion and resultantly activated protease].

When we assessed cytokine levels in both plasma and serum from the patients with atopic dermatitis and healthy volunteers, we found that IL-2, 5 and 10, and IFN-gamma were significantly elevated in the plasma from atopic dermatitis patients but not in their sera and that, in an average, each cytokine level, especially IL-2 level is far higher in plasma than in serum. In order to solve the cause for this dissociation. Calcium ion was dose-dependently added in the plasma in which calcium ion had been inactivated by citrate contained in the plasma.

[Oxidative injury and its defense system in vivo].

We and other researchers verified that excessively produced free radicals by neutrophils induce various diseases such as Behçet's disease, MCLS, SLE (neutrophil-stimulated lymphocytes), RA (synovial fluid neutrophils), Crohn's disease, colitis ulcerosa, and dermatitis herpetiformis (Dühring). Recently, it was reported that environmental toxic agents including herbicides such as paraquat, insecticides, nitrogen oxide, and ultraviolet radiation produce free radicals. Nitrogen oxide, a main product of the combustion of petroleum, is a prominent component of exhaust from automobiles.

Successful treatment of severe atopic dermatitis-complicated cataract and male infertility with a natural product antioxidant.

There has been a recent dramatic change in the features of atopic dermatitis and male infertility, including a marked increased prevalence of severe and treatment-resistant atopic dermatitis; an increase in severe atopic dermatitis complicated by cataracts, especially in urban and industrial areas; and an increase in the number of infertile men with poor sperm motility. Previously we have attributed these changes to the increased free radicals produced by environmental toxicity. We have reported the increase in lipid peroxide levels and decrease in superoxide dismutase inducibility in severe atopic dermatitis patients, and shown that lipid peroxides attach to the stratum corneum, promoting loss of skin moisturization and resulting in the worsening of atopic dermatitis.

Role of cytokines, tyrosine kinase, and protein kinase C on production of superoxide and induction of scavenging enzymes in human leukocytes.

We investigated the effects of proximal modulators of cytokines, tyrosine kinase (TK), and protein kinase C (PKC) on reactive oxygen species (ROS) generation and the induction of scavenging enzymes, superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) of human neutrophils and lymphocytes, by using IL1-alpha, TNF-alpha, and IFN-gamma and neutralizing antibodies to these cytokines. Inhibitors of TK (ST638 and herbimycin) or PKC (H-7, calphostin, and staurosporine) were also used. The results revealed that both (O2)- generation stimulated by five different agents (opsonized zymosan, A23187, PAF, PMA, and fMLP) and the inductions of all three scavenging enzymes were potentiated by priming with TNF-alpha.

Electromagnetic wave emitting products and "Kikoh" potentiate human leukocyte functions.

Tourmaline (electric stone, a type of granite stone), common granite stone, ceramic disks, hot spring water and human palmar energy (called "Kikoh" in Japan and China), all which emit electromagnetic radiation in the far infrared region (wavelength 4-14 microns). These materials were thus examined for effects on human leukocyte activity and on lipid peroxidation of unsaturated fatty acids. It was revealed that these materials significantly increased intracellular calcium ion concentration, phagocytosis, and generation of reactive oxygen species in neutrophils, and the blastogenetic response of lymphocytes to mitogens.

Age-dependent basal level and induction capacity of copper-zinc and manganese superoxide dismutase and other scavenging enzyme activities in leukocytes from young and elderly adults.

Several enzymes, including superoxide dismutase (SOD), catalase, glutathione peroxidase, and D-glucose-6-phosphate dehydrogenase are capable of scavenging reactive oxygen species in in vivo. We assessed both basal levels and the capacity of these enzyme activities to be induced in human leukocytes in response to a variety of agents. Basal activity of copper-zinc SOD, and manganese SOD showed little variation with age.

Why are natural plant medicinal products effective in some patients and not in others with the same disease?

We had previously found that the clinical efficacy of natural medicinal products was significantly enhanced by pretreatments of the natural compounds with far infrared radiation heating and brewing that effected degradation of high molecular polymers to yield free forms of low molecular monomers with anti-oxidant activity. The gastric samples from the patients were incubated with untreated or treated natural products, and the resulting materials assayed in vitro for the capacity to scavenge reactive oxygen species (ROS). The gastric fluid of patients who had responded to the untreated natural products showed a significantly greater scavenging ability than did the patients who had not responded to these agents.

Induction of superoxide dismutase in leukocytes by paraquat: correlation with age and possible predictor of longevity.

Reactive oxygen species (ROS) are thought to play a role in the aging process as well as in a number of human diseases states. Superoxide dismutase (SOD), an enzyme that scavenges the superoxide anion (O2-) is constitutively expressed in leukocytes and other tissues. When assayed in peripheral blood leukocytes (PBL), constitutive SOD activity shows little variation among individuals of different ages.

Neutrophil-potentiating factors released from stimulated lymphocytes; special reference to the increase in neutrophil-potentiating factors from streptococcus-stimulated lymphocytes of patients with Behçet's disease.

The potentiating effect of the soluble factors released from normal or diseased lymphocytes on neutrophil functions were investigated in the presence or absence of mitogens and wall preparations of Streptococcus pyogenes. When normal T lymphocyte populations were stimulated with T cell mitogens or with streptococcal preparations, the supernatants from these cultures potentiated neutrophil chemotaxis, phagocytosis and O2- generation. Upon gel-filtration of these stimulated lymphocyte supernatants, the neutrophil-potentiating activity was inactivated by trypsin or by a 30-min incubation at 130 degrees C, but was not affected by acid treatment at pH 2 or heat treatment at 56 degrees C for 60 min.

Lipid peroxides and superoxide dismutase (SOD) induction in skin inflammatory diseases, and treatment with SOD preparations.

In the skin ulcer or severely inflamed and erosive lesions induced due to burn, wounds and other dermatitides, lipid peroxides were markedly increased, with resultant cytotoxic effects in situ. Generally, superoxide dismutase (SOD), which scavenges oxygen radicals or inhibits lipid peroxidation, is adapted to be induced (increased) under oxygen toxicity. For the treatment of not only systemic inflammatory diseases but also skin ulcer lesions, especially due to burn and wounds, liposomal-encapsulated SOD injection was effective.