Chinese herbs for dementia diseases.

In the last twenty years a considerable body of information has accumulated on the chemical constituents of Chinese herbs and their therapeutic potential. Our evaluation/systematic review [1, 2] of well-designed, randomized double blind controlled trials on Chinese herbal medicines beneficial for the improvement of cognitive function revealed a range of either single herbs or herbal mixtures that provided neuroprotective benefits. Oxidative stress may directly initiate neurodegeneration and herbal antioxidant neuroprotection is considered as a preventative and therapeutic approach. We encountered Acoris gramineus rhizome (AGR), Panax ginseng, Polygala tenuifolia and Poria cocos as the four most frequently used herbs as single/herbal mixtures that were associated with positive cognitive enhancing outcomes. This review focuses on the evidence of their medicinal effects attributed to those constituents present in relatively high concentration.

Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases.

Evidence for the medicinal and health benefits of polyphenols in green tea for the prevention of chronic diseases such as heart disease, various types of cancer and neurodegenerative diseases is advancing. Their in vivo effectiveness and molecular mechanisms are difficult to elucidate and remain a challenging task. We review the redox responsiveness and amyloid protein perturbation biophysical properties of the major green tea polyphenol constituent (-)- epigallocatechin-3-gallate [EGCG].

Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer.

BACKGROUND: Cancer vaccines employing DC in their capacity as APC have been tolerated well and have shown some efficacy in clinical studies. IL-12, a cytokine critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL) differentiation, when released from a DC-based cancer vaccine, may support the generation of a cellular T-cell response. METHODS: We applied tumor cell lysate plus keyhole limpet hemocyanin (KLH)-loaded and 48-h lipopolysaccharide (LPS) plus IFN-gamma-stimulated fully mature DC, which do not release IL-12, subcutaneously to eight patients, and maximally 6-h stimulated semi-mature (sm) DC, which are potent producers of IL-12, subcutaneously (n=6) or intranodally (n=8) as a cancer vaccine to patients suffering from advanced solid pediatric malignancies. RESULTS: No serious adverse events were observed following application of IL-12-releasing smDC. Following immunization the majority of patients responded positively to KLH in a delayed-type hypersensitivity (DTH) test. In addition, three of six intranodally treated patients responded to the tumor Ag in the DTH test. DISCUSSION: We conclude that treatment with a DC-based cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe and feasible and has the potential to induce a cellular immune response in pediatric cancer patients.

Efficacy, chemistry and pharmacology of chinese herbal medicine for allergic rhinitis.

An extensive literature search identified six randomized controlled clinical trials in which the efficacy of Chinese herbal medicine had been investigated for the treatment of allergic rhinitis. Although four of these trials had methodological flaws, the therapeutic outcomes of all six have been reviewed. One of two trials considered to be of high quality was concerned with the treatment of seasonal allergic rhinitis and the other with perennial allergic rhinitis. It is considered that all six studies demonstrated various degrees of alleviation of the symptoms of allergic rhinitis. No serious side effects were reported in any of the trials. A number of the herbs in the Chinese herbal formulae used in the trials, and/or their constituent compounds have been reported to possess anti-allergic, anti-inflammatory or immune modulation activity. Such actions include inhibition of the release or action of mast cell mediators such as histamine, inhibition of inflammation induced by chemical agents, and modulation of serum IgE levels or of lymphocyte and/or macrophage activity. An aqueous, unresolved extract of the herbal formula used in one of the six trials has been reported to exhibit a range of pharmacological actions relevant to the treatment of allergic rhinitis. Essential oils, lignans, flavonoids and saponins are chemical classes that are frequently represented in individual herbs of the six Chinese herbal formulae used in the trials. The chemical structures characterising these classes of compound and the pharmacological actions of these and other constituents of the herbs, relevant to allergic rhinitis, have been reviewed.

[Stroke management on general medical departments. A multicenter study in Austria]. / Insultbehandlung an Internen Abteilungen. Eine österreichische Multizenterstudie.

BACKGROUND AND OBJECTIVE: Despite the claimed superiority of Stroke Units a majority of patients with acute stroke is still treated on general medical departments in many countries. In Austria 90 % of 121 medical departments state that they take care of stroke patients routinely or at least sometimes. Therefore, our aim was to evaluate whether stroke management on medical wards meets up-to-date standards. PATIENTS AND METHODS: 55 medical departments all over Austria participated in a prospective multicenter registry documenting diagnostics, treatment and the in-hospital course of unselected patients admitted with an acute stroke according to a standardised protocol. RESULTS: 1100 patients, 56 % female, with a median age of 75 years were assessed. Median hospital stay was 14 days. In 96 % a cranial computer tomogram was performed. 81 % of cerebral lesions were ischemic, 10 % haemorrhagic. Only 10 % had no risk factor or accompanying medical disease. 31 % suffered at least one medical and 18 % one neurological complication (p = 0.00000003). In-hospital mortality was 17 %, functional outcome was poor in 27 % (Rankin scale [RS] 4 or 5) and good in 56 % (RS 0-3). 74 % of discharged patients could leave to their home, 13 % were transferred to a nursing home and 13 % to a rehabilitation center. 95 % of surviving patients left on either an antiplatelet or an anticoagulant medication and 73 % received antihypertensives. CONCLUSION: Outcome of stroke patients treated on general medical departments seems to be fairly comparable to that commonly reported by neurological Stroke Units. Further improvements may be obtained by implementation of integrated "mixed assessment" units into medical departments.

Interaction of exercise and diet on GLUT-4 protein and gene expression in Type I and Type II rat skeletal muscle.

We determined the interaction of exercise and diet on glucose transporter (GLUT-4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum longus (EDL)] skeletal muscle. Forty-eight Sprague Dawley rats were randomly assigned to one of two dietary conditions: high-fat (FAT, n=24) or high-carbohydrate (CHO, n=24). Animals in each dietary condition were allocated to one of two groups: control (NT, n=8) or a group that performed 8 weeks of treadmill running (4 sessions week-1 of 1000 m @ 28 m min-1, RUN, n=16). Eight trained rats were killed after their final exercise bout for determination of GLUT-4 protein and mRNA expression: the remainder were killed 48 h after their last session for measurement of muscle glycogen and triacylglycerol concentration. GLUT-4 protein expression in NT rats was similar in both muscles after 8 weeks of either diet. However, there was a main effect of training such that GLUT-4 protein was increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in animals fed with CHO (P < 0.05). There was a significant diet-training interaction on GLUT-4 mRNA, such that expression was increased in both the soleus (100% upward arrowP < 0.05) and EDL (142% upward arrowP < 0.01) in CHO-fed animals. Trained rats fed with FAT decreased mRNA expression in the EDL ( downward arrow 45%, P < 0.05) but not the soleus ( downward arrow 14%, NS). We conclude that exercise training in CHO-fed rats increased both GLUT-4 protein and mRNA expression in type I and type II skeletal muscle. Despite lower GLUT-4 mRNA in muscles from fat-fed animals, exercise-induced increases in GLUT-4 protein were largely preserved, suggesting that control of GLUT-4 protein and gene expression are modified independently by exercise and diet.

[Histological diagnosis of inflammatory skin diseases. Use of a simple algorithm and modern diagnostic methods]. / Histologische Diagnostik entzündlicher Hauterkrankungen. Verwendung eines einfachen Algorithmus und moderner Methoden.

The histological diagnosis of inflammatory skin diseases on a day-to-day routine basis poses the difficult task to characterise a dynamic clinical process by histomorphological analysis of one single lesion. Very complex algorithms which are meant to lead to the correct diagnosis are difficult to use. To facilitate the process and reduce the number of algorithms the following method is proposed: 1. Histological examination under low power Definition of lesions altered by scratching 2. Localisation of the significant pathological alterations as follows: Changes in epidermis and dermis Blister formation Changes in dermis/subcutis without characteristic changes in the epidermis Changes mainly in the subcutis 3. Closer examination using a simple algorithm and planning of further investigations following defined criteria: In the case of changes in epidermis and dermis definition of spongiotic, psoriasiform or lichenoid dermatitis (Abb. 1). In the case of blister formation definition of the blister following the given algorithm (Abb. 1). In the case of changes in dermis/subcutis without characteristic changes in the epidermis after exclusion of vasculitis and lymphoma definition of the main pattern as lymphocytic, neutrophilic, eosinophilic, lymphoplasmocytic or granulomatous and following the given algorithm (Abb. 2). In the case of changes mainly in the subcutis after exclusion of vasculitis and lymphoma definition of the main pattern of panniculitis as septal or/and lobular (Abb. 2). Exclusion of PAS positive microorganisms and checking if the general pattern fits into infectious correlation. Use of clinicopathological correlation.

Panax ginseng and Eleutherococcus senticosus may exaggerate an already existing biphasic response to stress via inhibition of enzymes which limit the binding of stress hormones to their receptors.

A mechanism of action for Panax ginseng (PG) and Eleutherococcus senticosus (ES) is proposed which explains how they could produce the paradoxical effect of sometimes increasing and sometimes decreasing the stress response. The mechanism suggests that this biphasic effect results from increased occupancy of positive and negative feedback stress hormone receptors by their natural ligands due to inhibition of specific enzymes which function to limit receptor occupancy. Specifically, it is suggested that PG inhibits 11-beta hydroxysteroid dehydrogenase one and ES inhibits catechol- O -methyl transferase, both of which reside in close proximity to stress hormone receptors and catalyse the degradation of stress hormones into inactive compounds. In addition, it is suggested that the increased energy said to result from PG and ES may be a consequence of their increasing the occupancy of stress hormone receptors which function to redistribute the body's energy reserves from regeneration to activity.

The effects of Eleutherococcus senticosus and Panax ginseng on steroidal hormone indices of stress and lymphocyte subset numbers in endurance athletes.

A clinical trial was undertaken to investigate the effects of Eleutherococcus senticosus (ES) and Panax ginseng (PG) on competitive club-level endurance athletes engaged in their normal in-season training. Participants were matched for training stress and received a 33% ethanolic extract (8 mL/day) containing either ES, PG (equivalent to 4 g and 2 g/day of dried root, respectively), or a placebo. A pre-test and post-test were used to evaluate the effects of six weeks of supplementation on cortisol, testosterone, and testosterone to cortisol ratio (TCR) as well as circulating numbers of total T-cells, T-helper cells (CD4), T-suppressor cells (CD8), CD4 to CD8 ratio, natural killer cells, and B lymphocytes. None of the immune system variables changed significantly nor showed any clear trend from pre to post test in any of the treatment groups. No significant change in testosterone, cortisol or TCR was observed in the PG group. In the ES group, however, TCR decreased by 28.7% from 0.0464 to 0.0331 (P=0.03). The main contribution to this decrease appeared to be a non-significant (P= 0.07) 31% trend towards increased cortisol rather than a very small non-significant (P = 0.36) 7% decrease in the calculated mean for testosterone. This result suggested that contrary to initial expectation, ES increased rather than decreased hormonal indices of stress, which may be consistent with animal research suggesting a threshold of stress below which ES increases the stress response and above which ES decreases the stress response.

Benign fibrous histiocytoma (dermatofibroma) of the face: clinicopathologic and immunohistochemical study of 34 cases associated with an aggressive clinical course.

Thirty-four cases of fibrous histiocytoma (dermatofibroma) arising on the face are reported. These neoplasms occurred frequently in females (24 female, 10 male) and showed a broad age range (12 to 85 years; mean: 43.6 years, median: 41 years). The neoplasms originated on the forehead (nine cases), the cheek (eight cases), the eyebrow (four cases), the temporal region (three cases), the nose (two cases), and the ear (one case); in seven cases the location face was given only. Five of 27 cases with follow-up information (median: 5 years) recurred locally; in one case four recurrences were excised within 8 years. The majority of cases extended into the subcutis and deep soft tissue including striated muscle (50% of cases). Histologically, only the minority of cases was composed entirely of histiocytoid and spindle-shaped tumor cells arranged in a storiform growth pattern. In many cases cellular fascicles and bundles of spindle-shaped tumor cells were noted in addition to classical morphological features of fibrous histiocytoma. A moderate mitotic rate (mean: 2.97 mitoses in 10 HPFs) was observed, and in few cases increased atypia was evident. Frank tumor necrosis and/or vascular invasion were not identified. Immunohistochemical studies revealed Factor XIIIa positivity in 13 out of 17, focal CD68 positivity in 6 out of 10, and alpha-smooth muscle actin positivity in 16 out of 19 cases tested. These lesions should be distinguished from dermatofibrosarcoma protuberans, including its fibrosarcomatous variant, leiomyosarcoma, and low-grade myofibroblastic sarcoma. Cases of fibrous histiocytoma of the face have to be excised with wider margins in comparison with examples of classical fibrous histiocytoma occurring on the extremities because of diffuse infiltration, involvement of deeper structures, and an increased rate of local recurrences.

Propagation analysis of self-convergent beam width and characterization of hard-edge diffracted beams.

For a laser beam diffracted by a hard-edge aperture, propagation of the beam width, defined by the second-order moment of its irradiance distribution truncated according to the self-convergent-width criterion, obeys the familiar hyperbolic law. It is demonstrated numerically that, with the self-convergent-width approach, the beam-propagation parameters for three beam types (Gaussian, Hermite-Gaussian, and flattened Gaussian) diffracted by hard-edge apertures can be determined with the second-moment-based procedure that is recommended by the present draft standard only for unapertured laser beams.

Cystic sebaceous tumors as marker lesions for the Muir-Torre syndrome: a histopathologic and molecular genetic study.

Cystic sebaceous tumors (CST) are well-circumscribed, large, deeply located dermal sebaceous proliferations with a cystic growth pattern. We identified 12 CST in 8 of 19 patients with Muir-Torre syndrome (MTS). We interpret CST as a tumor spectrum with clearly benign cystic sebaceous adenomas at one end and proliferative atypical cystic sebaceous tumors at the other. When examining these proliferative atypical tumors on morphologic criteria alone, the possibility of an evolving cystic sebaceous carcinoma cannot be excluded. We have not observed recurrences or metastases, indicating that these lesions are not highly malignant carcinomas. In 10 of 12 cases of CST, we examined microsatellite instability (MSI). All 10 examined examples of CST from patients with MTS showed MSI characteristic for hereditary nonpolyposis colorectal cancer (HNPCC), which is caused by autosomal dominant inherited DNA mismatch repair (MMR) defects. Mutational analysis of the MMR genes hMSH2 and hMLH1 had revealed different germline mutations in the hMSH2 gene in three of six examined patients with MTS with CST. We then found four more CST in patients without a history of internal malignancy. All four CST exhibited MSI. By mutational analysis in one of these patients we identified a truncating germline mutation in the MMR gene hMLH1. We conclude that CST is a marker for the mismatch repair-deficient subtype of MTS with a high risk for later internal malignancies. By recognizing CST, the histopathologist can suggest the great likelihood of MTS to the clinician.

A new application of BCG antibody for rapid screening of various tissue microorganisms.

BACKGROUND: In routine dermatopathology there is growing demand for a simple, fast, cost-effective, and highly sensitive screening tool for the detection of microorganisms. OBJECTIVE: Our purpose was to determine whether immunostaining with polyclonal anti-Mycobacterium bovis (BCG), which is known for its interspecies cross-reactivity, is a suitable screening method for many common microorganisms in dermatopathologic specimens. METHODS: A total of 254 formalin-fixed, paraffin-embedded skin specimens of viral, protozoal, fungal, and bacterial infections were stained with appropriate histochemical stains and with anti-BCG. RESULTS: Anti-BCG labeled bacteria and fungi with high sensitivity and minimal background staining, but did not react with spirochetes, viruses, or protozoa (Leishmania). The quality and sensitivity of anti-BCG staining were superior to conventional histochemical stains. CONCLUSION: Because of its cross-reactivity with many bacteria and fungi as well as its high sensitivity and minimal background staining, the anti-BCG immunostain is a promising screening tool for the detection of the most common bacterial and fungal microorganisms in paraffin-embedded skin specimens.

Absence of anaplastic lymphoma kinase (ALK) and Epstein-Barr virus gene products in primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis.

The prevalence of the t(2;5)(p23;q35) and/or anaplastic lymphoma kinase (ALK) gene products in cutaneous anaplastic large cell (ALC) lymphomas and a potential precursor lesion, lymphomatoid papulosis (LyP), is controversial. ALK gene products, which are absent from normal lymphohaematopoietic cells, are a phenotypic marker of lymphomas carrying the t(2;5). We used in situ hybridization and immunohistology to screen 14 cutaneous ALC lymphomas, 21 cases of LyP, and one nodal ALC lymphoma associated with LyP for ALK gene products. ALK gene products were not detectable in these cases. In contrast, ALK gene products were found in a lymphonodal ALC lymphoma with subsequent extension to the skin and in t(2;5)-positive cell lines. Detection of the Epstein-Barr virus (EBV)-encoded small nuclear transcripts (EBER), and of immunoglobulin light chain transcripts served to check for the presence of cellular RNA in the tissue sections. EBER transcripts were found in scattered reactive lymphoid cells, but not in atypical or tumour cells. ALK gene expression and EBV infection seem to be a rare finding in cutaneous ALC lymphomas and LyP. This points to a molecular aetiology of primary cutaneous ALC lymphomas and LyP distinct from that of extracutaneous CD30+ lymphoproliferative disease. Detection of the t(2;5) or ALK gene products in cutaneous lymphoproliferative lesions therefore requires exclusion of extracutaneous ALC lymphoma in such patients.

Cutaneous adult myofibroma: a vascular neoplasm.

Infantile myofibromatosis is a distinctive type of fibromatosis that usually develops during the immediate perinatal period. There are variants with solitary and multiple tumors. Lesions confined to the skin, soft tissue, and bone carry a good prognosis, showing spontaneous regression. The prognosis, however, is much less favorable when visceral lesions are present and the outcome may be fatal. Only recently it became obvious that there is an adult counterpart of infantile myofibromatosis, characterized by solitary lesions that have a predilection for involve the dermis and show no tendency to regression, although they have an entirely benign biological behavior. These lesions have been named cutaneous myofibroma or solitary myofibroma of adults. We have studied the clinical, histopathological and immunohistochemical characteristics of 53 examples of cutaneous adult myofibroma. In addition, 2 cases were examined ultrastructurally. The patients were mostly adults with ages ranging from 6-83 years. The lesions presented as solitary, usually painless nodules of variable duration on the skin, usually located on the extremities. Histopathologically, four patterns were identified: nodular or cellular type, multinodular or biphasic type, leiomyoma-like or fascicular type, and vascular type. A correlation between the histopathologic pattern and the lesional age was observed: vascular type of cutaneous adult myofibroma in early lesions, nodular and multinodular lesions in fully developed lesions, and leiomyoma-like or fascicular type in late lesions. Immunohistochemically, the spindle cells were desmin negative, but expressed immunoreactivity for vimentin, pan-smooth muscle actin, and alpha-smooth muscle actin. Ultrastructurally, neoplastic cells showed characteristics of undifferentiated mesenchymal cells with features of fibroblasts, myofibroblasts and pericytes. Primitive vascular formations were seen in the form of irregular clefts between adjoining cells. We conclude that cutaneous adult myofibroma is a little-known benign vascular neoplasm probably derived from myopericytes.

[Desmoplastic malignant melanoma. Clinical and histopathologic results of a study in 34 patients]. / Das desmoplastische maligne Melanom. Klinische und histopathologische Ergebnisse einer Studie von 34 Patienten.

Clinical and histopathological findings of 34 cases of desmoplastic malignant melanoma (DMM) are summarized and compared to the literature. DMM develop mostly in sun damaged skin of elderly patients, they are rare and often nonpigmented tumors that are difficult to diagnose clinically. In all cases the tumor parameters showed level IV or V melanomas (level IV: 55.9%, level IV-V: 14.7%, level V: 29.4%) and the tumor thickness measured 3.85 mm +/- 2.31 mm (1.0-11.0 mm). In 22 cases, the follow-up time was between 2 and 7 years. Local recurrences were observed in 7 ( = 31.8%) patients, metastases in 4 ( = 18.2%) and tumor-related deaths in 3. The prognosis for our patients seems to be slightly better than that described in the literature. The main reason is an improved histological diagnosis of this special type of melanoma. Using immunohistochemical staining with anti-S100 antibody it is possible to establish the melanocytic nature of these fibrotic spindle cell tumors earlier that is, in small initial biopsies, and tumor margins can be defined more accurately. As a consequence, surgery is done earlier and is more likely to be curative.

Characterization of the chicken brain melatonin-binding protein using iodinated and tritiated ligands.

The melatonin-binding protein in chicken brain membranes was characterized using both [125I]-2-iodomelatonin and [3H]-melatonin as radioligands. Saturation studies conducted at 25 degrees C revealed a single class of binding site with dissociation constants of 24 +/- 4.8 pM (n = 7) and 125 +/- 21 pM (n = 6) for the iodinated and tritiated ligands, respectively. Calculation of the affinity constant using data from kinetic experiments gave values of 2.2 +/- 0.4 pM and 135 +/- 15 pM for the iodinated and tritiated ligands, respectively. Competition studies showed that the rank order of inhibition of binding by melatonin analogues was similar for both radioligands (2-iodomelatonin > melatonin > 2,3-dihydromelatonin > N-acetyl-5-methoxykynurenamine > N-acetylserotonin > 5-methoxytryptamine). The calculation of Ki, which depends upon the affinity constant, was 22 +/- 4.9 pM and 129 +/- 21 pM for 2-iodomelatonin and melatonin, respectively, when the affinity constant derived from the [125I]-2-iodomelatonin saturation experiments was used, but 4.9 +/- 1.5 pM and 33 +/- 5.5 pM when the kinetically derived constant was used. When [3H]-melatonin was used, the Ki for melatonin was 72 +/- 8 pM and 20 +/- 4.6 pM for 2-iodomelatonin and melatonin. Binding of [125I]-2-iodomelatonin to the membranes was partially reversible at 25 degrees C in contrast to the complete reversibility of [3H]-melatonin. Examination of the effects of temperature on binding indicated that at 37 degrees C both association and dissociation of both ligands were accelerated. Closer examination showed that at 37 degrees C there was a loss of approximately 40% of the [125I]-2-iodomelatonin binding sites and little influence upon the affinity of binding with time. By contrast, when [3H]-melatonin was used, the affinity decreased fourfold, with only a slight change in the number of sites. If membranes were incubated at 37 degrees C and then switched 25 degrees C, binding increased, emphasizing the fact that the binding sites were not destroyed. Whereas there appears to be little doubt that 2-iodomelatonin is a biologically active melatonin agonist, the binding of the radioactive form of this agonist to the putative melatonin receptor binding site is quite different from that of the endogenous ligand. This may have serious consequences in studies where receptor content is determined following physiological or pharmacological interventions.

[Differences between plaque-like variants of dermatofibrosarcoma protuberans and plaque-like dermal fibromatosis (dermatomyofibroma)]. / Die Unterschiede zwischen der plaqueförmigen Variante des Dermatofibrosarcoma protuberans und der plaqueförmigen dermalen Fibromatose (Dermatomyofibrom).

On the basis of two cases the differences between the plaque-like variant of dermatofibrosarcoma protuberans (PDFSP) and the plaque-like dermal fibromatosis (synonym: dermatomyofibroma; PDF) are presented. PDFSP and PDF are two clinically very similar dermal fibrous proliferations, but differentiation is important because of their different therapy and prognosis. Histologically and immunohistochemically PDFSP and PDF can be recognized as separate entities.