Local hyperthermia of N2/N3 cervical lymph node metastases: correlationof technical/thermal parameters and response.

PURPOSE: Patients with advanced head and neck carcinomas, primarily nonresectable as well as recurrent cases, were treated in multimodality regimens with radiotherapy, chemotherapy, and local hyperthermia. Commercially available microwave and radiowave applicators were used in 50 patients with N2/N3 cervical lymph node metastases during more than 250 heat treatments. To assess technical suitability, the achieved power densities and thermal parameters were tested for correlation with anatomical and geometrical factors. To assess effectiveness, the response was compared with derived parameters of the achieved temperature distributions. METHODS AND MATERIALS: The temperature measurement points (in thermometry catheters) documented by computerized tomography are labeled according to tissue depth, shielding by osseous structures, and location in relation to the external applicators. Relative and absolute specific absorption rates (SAR) and cooling coefficients are extracted from the temperature-time curves. Time-averaged temperature-position curves are evaluated to obtain index temperatures (T90, T50, T20), minimum/maximum tumor temperatures, cumulative minutes T90 > or = 43 degrees C, and 43 degrees C-equivalent min T90. Radiation dose, treatment time, and chemotherapy regiment are also considered. A response parameter is defined using the pre- and posttherapeutic tumor volumes. A multivariate variance analysis is performed for the dependent variables power density, thermal parameters, and response. RESULTS: A significant correlation exists between power density and absorption, presence of a fat layer, and applicator illumination. The maximum depth is 5 cm, where SAR of >= 10 mW/g are registered. Achieved temperatures at individual measurement points are dependent on the SAR, and to a lesser extent, the perfusion-dependent cooling coefficients, but the index temperature T90 is only significantly related to intratumorally achieved SAR. The thermal gradient (T20-T50) and temperature peak (T20) are significantly influenced by the tumor volume. The response is directly related to the index temperature T90, equivalent minute T90 43 degrees C, and cumulative minutes T90 > or = 40.5 degrees C, and inversely related to the tumor volume. CONCLUSIONS: Local hyperthermia using microwave and radiowave applicators in the head and neck region is a tolerable and clinically practical supplementary therapy used as part of multimodal regimens, and has already been proven to be effective. However, the analyses also demonstrated the limits of currently available technology, and confirm the need for continued methodical research.

Free radical scavenging by ethanol extract of propolis.

The free radical scavenging ability of an ethanolic extract of propolis (EEP) was demonstrated by electron spin resonance spectroscopy, when 2,2-diphenyl-1-picrylhydrazyl (DPPH) was treated with increasing concentrations of EEP. It was shown that the DPPH signal intensity was inversely related to the EEP concentration and to the reaction time. It is assumed that the ability of components in EEP to donate a hydrogen atom is responsible for the lowering of the DPPH-EEP signal, and reflect the anti-oxidative nature of EEP.

Structure-activity relationship in the ability of flavonols to inhibit chemiluminescence.

Fourteen flavonoids were evaluated for their ability to inhibit chemiluminescence, either of neutrophils that had been briefly exposed to both luminol and phorbol-myristate acetate or to an enzymatic system with H2O2, luminol and horseradish peroxidase. Using chemiluminescence as the quantitative parameter, it can be concluded that the hydroxyl group in position 3 of the flavonols is vital for their inhibitory effect, and that two hydroxyl groups on the phenyl ring are optimal for such an effect. It was also noted that the C2-C3 double bond is essential for the flavonols' anti-oxidative effect. It is suggested that the ability of flavonols to suppress chemiluminescence is reciprocally correlated with their lipophilicity.

Inhibition of neutrophils' chemiluminescence by ethanol extract of propolis (EEP) and its phenolic components.

Ethanol extract of propolis (EEP), a natural beehive product, has been known for centuries for a variety of beneficial traditional medical properties, among which an anti-inflammatory effect is a major one. Now that most of its components have been isolated and recently identified, we tested 19 of them (all phenolic compounds) for their degree of anti-inflammatory activity. This was performed by evaluating the luminol-enhanced chemiluminescence, formed after their scavenging free radicals, generated by neutrophils that had been stimulated by phorbol myristate acetate. Caffeic-acid-phenylethyl-ester abolished the chemiluminescence completely at a concentration of 10 microM, while three flavone derivatives and three flavonols (galangin, kaempferol and kaempferid) diminished this chemiluminescence by 73-93% at the same concentration. These results indicate that some of the phenolic components of the ethanol extract of propolis are its active components in exerting its renowned anti-inflammatory activity.

Effects of ethanol extract of propolis (EEP) and its flavones on inducible gene expression in J774A.1 macrophages.

Propolis, a bee-hive product, has been used in folk medicine for centuries, and recently in modern medicine as an anti-inflammatory and immunomodulatory agent. These activities would be mainly due to phenolic compounds such as flavonoids, especially flavone derivatives. The present study examined the effect of ethanol extract of propolis (EEP) and selected flavone derivatives (chrysin, galangin, kaempferol and quercetin) on interleukin-1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) gene expression in lipopolysaccharide (LPS)-induced J774A.1 macrophages. Treatment of cells with EEP significantly suppressed both IL-1beta mRNA (P<0.02) and iNOS mRNA (P<0.001) expression. The concentrations of cytokine in cell culture supernatants and cell lysates and nitric oxide (NO) generation were reduced in a dose-dependent manner. The tested phenolic compounds significantly decreased the IL-1beta mRNA level and IL-1beta protein concentration (P<0.05) (excluding galangin), iNOS mRNA level and NO production (P<0.001). The most potent inhibitor of the IL-1beta synthesis and NO generation was chrysin. These results indicate that EEP exerts its inhibitory effect on the IL-1beta and iNOS gene expression in J774A.1 macrophages at the transcriptional level. Tested flavone derivatives contribute to the anti-inflammatory activity of propolis.

Increased risk of acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in a county of Hesse, Germany.

The incidence of acute and chronic myelogenous leukemia has been compared for the two neighbouring regions of Marburg and Giessen in Hesse (Germany). The investigation was based on the incident cases of the years 1983-1989 which have been diagnosed in the hematological departments of the universities of the two regions. The epidemiological evaluation of the data has been carried out in terms of a historical follow-up study, and shows an increased relative risk for the region around Marburg with a particular elevation for one community within this region. Potential determinants are discussed and focus on trinitrotoluene (TNT) and decomposition products which are known to contaminate the soil of this community, in some places severely, due to insufficient removal of remnants of the TNT production in large underground plants during World War II.

Modulating luminol-dependent chemiluminescence of neutrophils by flavones.

The effect of 14 flavones on luminol-dependent chemiluminescence of neutrophils was studied in vitro. Chemiluminescence was used in this study as an indicator for the production of a reactive oxygen species by neutrophils, stimulated by phorbol myristate acetate. While flavone-8-acetic acid, and most of the compounds tested, inhibited chemiluminescence, flavone and its 5-hydroxy-7-methoxy derivatives enhanced it by up to 150%. The most active inhibitors of photon emission were the glycosides. These results indicate that lipophilicity and some structural determinants modulate the chemiluminescent capacity of neutrophils.

Effect of cinnamic and acrylic acids' derivatives on luminol-enhanced chemiluminescence of neutrophils.

Fourteen derivatives of cinnamic and acrylic acids were evaluated for their ability to modulate chemiluminescence, evoked by neutrophils that had been exposed to luminol and phorbol-myristate-acetate. Compounds with one or two hydroxyl groups on the phenyl ring demonstrated significant inhibition of the chemiluminescence, but this inhibition was diminished by methoxylation. Saturation of the double bond in the aliphatic chain of cinnamic acid at C6-enhanced the chemiluminescence to a small degree. All three acrylic acid derivatives demonstrated a marked inhibition of the luminol chemiluminescence, indicating that characteristics of the heterocyclic ring is of utmost importance in this activity.

Antitumoral effect of bleomycin+dolomite combination treatment, in mice bearing Ehrlich ascites carcinoma.

Dolomite, a mineral composed of magnesium and calcium carbonates, potentiates the antitumoral activity of bleomycin: While 40 days after inoculation, no mice survived the Ehrlich ascites tumor burden, 44% of them survived it after bleomycin treatment, and 63% after a simultaneous treatment of bleomycin and dolomite. The beneficial antitumor effect of dolomite is probably related to its high content (12.8%) of magnesium.

The ability of ethanolic extract of propolis (EEP) to protect mice against gamma irradiation.

Ethanolic extract of propolis (EEP) was tested as a protective agent against gamma irradiation in mice. The mice were exposed to 6 Gy gamma irradiation from a 60Co source, and were treated intraperitoneally with EEP, administered before and after their irradiation. While the non-treated mice expired within 12 weeks, the mice that received a series of EEP treatments survived the irradiation, and their leucocyte count as well as their spleens' plaque-forming activity returned to normal. It is suggested that an antioxidant and a free radical scavenger in the EEP are responsible for the radiation protective effect of the extract of this natural product.

Antitumoral property of ethanolic extract of propolis in mice-bearing Ehrlich carcinoma, as compared to bleomycin.

Antitumoral effect of ethanolic extract of propolis (EEP) was demonstrated in mature mice-bearing Ehrlich carcinoma. Survival rate after EEP treatment was compared to that of bleomycin, given alone or in combination every two days for 36 days and followed up for 14 additional days. The survival rate at 50 days was 55% after EEP and 40% after bleomycin, while all the mice-treated with EEP + bleomycin combination demonstrated shorter survival than the controls. It is concluded that while the in vivo activity of bleomycin is reduced in the presence of cytochrome-C-reductase inhibitors (like some of the EEP components are), the antitumoral property of EEP in the tumored animal model studied is significant and lasting.

Synergism between ethanolic extract of propolis (EEP) and anti-tuberculosis drugs on growth of mycobacteria.

Ethanolic extract of propolis exerts a strong anti-bacterial activity, in addition to antifungal, antiviral and antiprotozoal properties. In previous studies from these laboratories we have demonstrated that the intensity of the bactericidal activity of EEP is correlated with the virulence of the mycobacteria tested, and that EEP has a synergistic effect with antibiotics on growth of staphylococcus aureus. In the present study we investigated whether the same synergism and correlation exists between EEP and some anti-tuberculosis drugs on tuberculosis mycobacteria with different degrees of virulence. Six standard strains and 11 wild strains of mycobacteria were exposed for 30 days to EEP, with or without streptomycin, rifamycin, isoniazid or ethambutol. Out of the 17 strains, 8 were resistant to at least two standard antibiotics, and were considered "multi-resistant strains". The rest were either susceptible or resistant to only one of the antimycobacterial drugs. Antagonism was recorded only in one case, when Staphylococcus aureus were treated with a mixture of EEP and ethambutol, suggesting that a chemical bond could have been formed between this anti-tuberculosis antibiotic and one of the active components of the ethanol extract of propolis.

Correlation between virulence of various strains of mycobacteria and their susceptibility to ethanolic extract of propolis (EEP).

Ethanol extract of propolis (EEP) has antibacterial, antiviral, antiprotozoal and antifungal properties, in addition to many biological effects. Our laboratory has demonstrated a synergistic effect of EEP and antibiotics on the growth of Staphylococcus aureus, and suggested that the bactericidal effect of EEP was expressed mainly on virulent mycobacteria rather than on non-virulent (attenuated) ones. The present study was designed to reconfirm the latter finding, by subjecting 17 different mycobacteria strains to EEP, and evaluating whether there is a correlation between the virulence of the mycobacteria strains studied and their susceptibility to EEP. Our findings demonstrate that while the four non-virulent strains studied are not susceptible to EEP, out of the 13 virulent strains studied seven are susceptible and six are resistant to it. These results suggest that while there is no full correlation between virulence of the mycobacteria tested and their susceptibility to EEP, the few strains that were resistant to EEP were non-virulent.

[Evaluation of selected immunological parameters in alcohol dependence syndrome]. / Ocena wybranych parametrów immunologicznych u pacjentów z zespolem zaleznosci alkoholowej.

In 28 patients with alcohol dependence syndrome (ADS) the study of selected immunological parameters (percentage of peripheral blood lymphocytes CD3+, CD4+, CD8+, CD19+; lymphocyte transformation without and with phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM); chemiluminescence of peripheral blood granulocytes stimulated with phorbol myristate acetate (PMA)) and Instytut Mérieux' skin tests (Multitest CMI) were performed. The results of immunological parameters were connected with activity of liver enzymes (aspartate aminotransferase (ASP), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT). The differences of reactivity of immune system in the tested groups of patients were observed.

[Evaluation of selected immunological and biochemical parameters of blood in alcohol dependency]. / Ocena wybranych parametrów immunologicznych i biochemicznych krwi w zespole zalenosci alkoholowej.

The aim of this study was evaluation of selected immune humoral indicators in connection with biochemical parameters of blood in 28 alcohol dependent men. Increased activity of liver enzymes: AspAT in 53,6% of patients, A1AT in 46,4%, GGTP in 25% were found. Macrocytosis in 29% of patients was observed. There were also abnormal changes of immune proteins concentration: IgM, IgG, IgA, C3, C4 respectively in 60,7%, 46,4%, 21,4%, 42,9%, 10,7% of patients. In the group of patients with normal values of AspAT, GGTP, MCV; abnormal levels of humoral indicators concentration were observed. The correlation between immune proteins concentration and biochemical parameters was not found. The authors conclude that changes of determined immunological parameters may be used as prognostic indicators in disturbances in the alcoholics' immunity system.