Apparatus for measurement of thermoelectric properties of a single leg under large temperature differences.

Thermoelectric (TE) devices operate under large temperature differences, but material property measurements are typically accomplished under small temperature differences. Because of the issues associated with forming proper contact between the test sample and the electrodes and the control of heat flux, there are very few reports on large temperature difference measurements. Therefore, practically relevant performance parameters of a device, namely, power output and efficiency, are estimated by temperature averaging of material properties, whose accuracy is rarely validated by experimental investigations. To overcome these issues, we report an apparatus that has been designed and assembled to measure the TE properties-Seebeck coefficient, electrical conductivity, thermal conductivity, and power output and efficiency of a single thermoelectric material sample over large temperature gradients. The sample holder-a unique feature of this design-lowers the contact resistance between the sample and the electrodes, allowing for more accurate estimates of the sample's properties. Measurements were performed under constant temperature differences ranging from 50 to 300 K with the hot side reaching 673 K on a metallized Mg2Si0.3Sn0.7 leg synthesized in the laboratory. To simulate practical operating conditions of a continuously loaded generator, continuous current flow measurements were also performed under large temperature differences. The temperature-averaged TE properties from standard low temperature difference measurements and the experimental TE properties agree with each other, indicating that the designed setup is reliable for measuring various thermoelectric generator properties of single TE legs when subjected to temperature gradients between 50 and 300 K.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Expression of advanced glycation end-products and NFκB in chick embryos exposed to dioxins and treated with acetylsalicylic acid and α-tocopherol.

Dioxins have adverse and multifaceted effect on body functions. They are known to be carcinogens, immunotoxins, and teratogenic agents. In vivo, transformation of dioxins occurs after their interaction with the aryl hydrocarbon receptor (AhR) and leads to formation of proinflammatory and toxic metabolites. The aim of this study was to verify whether α-tocopherol (vitamin E) and acetylsalicylic acid (ASA), could reduce the damage caused by the action of dioxins. Fertile chicken eggs were injected with a solution of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), followed by the injection of α-tocopherol or acetylsalicylic acid. Organs such as heart and liver were dissected from the chick embryos at d 13 and 19 of development and subjected to immunohistochemical analysis of presence of advanced glycation end products (AGEs) and nuclear factor kappa B (NFκB) in tissues. The AGEs were used as the marker for exposure to dioxins, since it is well established that their level increases in dioxin-damaged tissues. Formation of AGEs was evaluated in embryos exposed to dioxin and treated with vitamin E and/or ASA (against dioxin-exposed, untreated controls). We have found that TCDD causes developmental disorders and increases the level of AGEs in chick embryo tissues. The use of such pharmacological agents as vitamin E, ASA, and combination of ASA and vitamin E, inhibited formation of the AGEs in 13-day-old embryos and reduced the AGEs level in embryos after 19 d of the development.

Photodynamic therapy with green light for the treatment of vulvar lichen sclerosus - Preliminary results.

INTRODUCTION: The standard treatment for lichen sclerosus (LS) is symptomatic and is primarily based on the chronic use of corticosteroids, sometimes resulting in unsatisfactory effects. Therefore, other non-pharmacological methods are being sought, which are less aggravating for the patient. LS can be treated topically by using photodynamic therapy (PDT) based on 5-aminolevulinic acid (5-ALA). Unfortunately, therapy with the red light is often connected with severe local pain during the illumination. Green light can also be characterised by its ability to turn on photodynamic reactions in cells. MATERIALS AND METHODS: The aim of this study was an evaluation into the efficacy and tolerance of 5-ALA-PDT with a green light (540nm±15nm) in 11 patients with chronic LS that were characterised by severe itching. The disease lasted from 1.5 to 4 years. All the patients were treated with three sessions of PDT. RESULTS: Following treatment with PDT, a significant improvement of local status, as well as a reduction of the main symptom (pruritus), were observed. No patient complained of severe pain during the sessions that would have required an interruption of irradiation or local application of analgesics. CONCLUSIONS: Our preliminary results of using green light in PDT for superficial skin non-oncological lesions are very promising but require further studies.

Nuclear osteopontin-c is a prognostic breast cancer marker.

BACKGROUND: Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. METHODS: Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. RESULTS: We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. CONCLUSIONS: The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis.

Photodynamic therapy of vulvar lichen sclerosus et atrophicus in a woman with hypothyreosis--case report.

Lichen sclerosus et atrophicus (LSA) is disease of skin and mucosa, its pathogenesis remains unknown. Itching, pain and burning sensations and atrophy of vulva impair quality of life. Treatment is symptomatic. We report case of 30-year old woman with lesions in vulva in which series of topical PDT were carried out. We applied Levulan®Kerastick® for 4h and after that lesions were illuminated with red light. Along with above treatment patient started receiving Euthyrox®, because of recently diagnosed hypothyreosis. Significant relief from subjective symptoms was achieved and lesions in vulvar region disappeared. Combination of topical PDT with hormonal therapy allowed controlling course of disease and minimizing symptoms, and thus improved quality of life.

Improvement of spatial resolution for local Seebeck coefficient measurements by deconvolution algorithm.

A potential Seebeck microprobe apparatus is described such that a profile of Seebeck coefficients can be detected on a material sample surface for thermopower investigations. Due to its spatially resolved limit on detecting small inhomogeneities of dopants or composition changes, we here propose a constructive combination of numerical modeling and practical measurement to improve the spatial resolution by deconvolution algorithm. The relevant transfer function, obtained from numerical calculations, was successfully applied on real measurement data. Besides, an improvement in detecting the 1.5 microm inhomogeneity has been achieved by applying one transfer function of the known tip setup on a set of Seebeck line scan signals, obtained with 6 microm tip-sample contact length, 3 micros signal capture time after contact, and 0.75 microm scan period. The result showed that a system theoretical approach in terms of deconvolution algorithm could theoretically enhance the spatial resolution anyway, but is practically limited by the systemic preconditions (tip size, signal capture time, and scan period) and the signal to noise ratio of the captured thermovoltages. Therefore, we provide a clear understanding of systemic preconditions and their impacts on the detection of small inhomogeneities and thus the performance in the thermopower analysis.

Quantification of the mRNA encoding Tumor Necrosis Factor alpha (TNFalpha) and its receptors in human nasal polyps.

PURPOSE: The object of the study was to assess the expression of the genes encoding TNFalpha and its receptors (TNF-R1 and TNF-R2) in patients with nasal polyps (NP). MATERIAL AND METHODS: The number of the mRNA copies was assessed by QRT-PCR in RNA extracts from 16 eosinophilic (ENP) and 5 neutrophilic nasal polyps (NNP), and 9 normal mucosa (NM) samples. The expression of corresponding proteins was demonstrated using immunohistochemistry. RESULTS: The mean level of mRNA copies for TNFalpha in ENP (82229c/microg) was not significantly higher when compared with controls (74869c/microg). NNP demonstrated significantly lower mean TNFalpha gene expression (7021c/microg) than the controls (p<0.05). A statistically higher mRNA TNFalpha copy number in ENP than in NNP was also revealed (p<0.01). A noticeably lower mRNA expression of TNF-R1 in ENP and NNP was seen as compared to the control group (10198c/microg vs. 30749c/microg, p<0.05 and 3440c/microg vs. 30749c/microg; p<0.05 respectively). In ENP the mean TNF-R2 mRNA copy number was markedly higher than in NNP (185c/microg vs. 7.6c/microg, p<0.05). TNF-R2 mRNA level did not differ significantly between ENP and the control group (185c/microg vs. 469c/microg). TNF-R1 expression was significantly higher than TNF-R2 at the mRNA (p<0.01) and protein (p<0.05) level both in ENP and NNP. No significant correlations in proteins expression were detected between ENP and NNP. CONCLUSIONS: TNF-R1 has been identified to be a prevalent form of the TNFalpha receptor in nasal polyps which may reflect the apparent dominance of this form in TNFalpha signalling. The findings raise the possibility that the eosinophils from NP may influence biological responses through TNFalpha-dependent mechanisms. The differences between ENP and NNP relating to TNFalpha and the expression of its receptors may reflect the distinct character of those diseases.

[The significance of TU M2-PK tumor marker for lung cancer diagnostics].

The purpose of the study was to investigate significance of the tumor marker pyruvate kinase Tumor M2 (Tu M2-PK), in diagnostics, monitoring of treatment, and evaluation of its effectiveness in patients with lung cancer (LC). This is an isoform of the glycosile enzyme pyruvate kinase, existing as an active dimer and less active tetramer. The expression of the less active form is typical of tumor cells; its blood level can be measured. The subjects of the study were 140 patients with LC of various histologic types. Serum levels of certain tumor markers (Cyfra 21-1, NSE, SCC, and Tu M2-PK) were measured; Tu M2-PK level was determined by ELISA test from ScheBoTech, a two-stage sandwich immunoassay using one type of antibodies. The marker concentration was also determined in 195 healthy volunteers (control group.) The maximum concentration of Tu M2-PK was 12.9 U/ml, determined with 95% specificity. 78% of the patients with small-cell carcinoma, 73% of patients with adenocarcinoma, and 81% of patients with non-small cell lung carcinoma displayed increase of Tu M2-PK serum concentration; this concentration was within normal limits in patients with nonmalignant diseases (e.g. bronchitis or tuberculosis). Thus, patients with lung carcinoma display a pathologic increase of Tu M2-P level. Measurement of Tu M2-P may be useful in patients with suspected LC; this marker may be of greater diagnostic significance than SCC or NSE.

Photodynamic therapy combined with a cysteine proteinase inhibitor synergistically decrease VEGF production and promote tumour necrosis in a rat mammary carcinoma.

OBJECTIVES: Photodynamic therapy (PDT) and inhibition of cathepsin B proteases by cystatin (cysteine proteinase inhibitor, CPI) are potential new tumour treatment modalities. We have investigated the efficacy of PDT and CPI alone and in combination on a solid mammary carcinoma transplanted into Wistar rats. MATERIALS AND METHODS: Intraperitoneally injected single doses of chlorine e6 or HpD as photosensitizers were excited at 630 nm (90 J/cm(2)). CPI (500 micro g per animal) was injected around the tumour daily during the 8-day treatment. Inoculation of tumour was either on day 1 of the protocol, or 8 days before. On day 8, tumour size was measured, tumour necrosis and vascularization were determined based on haematoxylin and eosin (H&E)-stained sections and serum vascular endothelial growth factor (VEGF) levels measured using an enzyme-linked immunosorbent assay kit. RESULTS: No differences (two-way anova) were found for treatments started with various time lags. At doses where CPI or PDT alone had no or negligible effect, their combination caused a marked (P < 0.001) decrease in serum VEGF, paralleled by a significant decrease in tumour size and number of capillary vessels, and a significant increase in necrosis (up to 80% of the tumour tissue). CONCLUSIONS: The combination of PDT and CPI could be a useful approach in tumour therapy as the two agents appear to be synergistic and probably decrease VEGF production by the tumour tissue.

Behavior of silica particles introduced into an isolated rat heart as potential drug carriers.

Silica powders consisting of small spherical particles (50-200 nm) have been obtained by the sol-gel method. A suspension of such particles in the Krebs-Hanseleit solution has been introduced into the coronary circulation of a beating perfused rat heart. The influence of the suspension on the heart muscle and the coronary vessels in the rat body has been histopathologically examined. The particles have not left the lumen of the vessels and have not caused any side effects. These observations suggest the possibility of using such silica particles as a carrier for selected drugs.

The combined treatment of transplantable solid mammary carcinoma in Wistar rats by use of photodynamic therapy and cysteine proteinase inhibitor.

Numerous studies have shown that lysosomal proteinases play an important role in carcinogenesis. The enzymatic activity of tumor-associated proteases is counter-balanced by specific inhibitors. Photodynamic therapy (PDT) is a technique which involves photoexcitation of sensitizing drugs retained in neoplastic tissue that is subsequently destroyed. Intraperitoneal injections of hematoporphyrin derivative (HpD) were given at a dose of 20 mg/kg in rats transplanted with mammary carcinoma. A halogen lamp was used 24 hours later at 630 +/- 20 nm and total dose--200 J/sq.cm. Cysteine proteinase inhibitor (CPI) was dissolved in saline and injected subcutaneously in doses of 50 mg and 200 mg per animal. The effectiveness of the treatment was evaluated with regard to survival time and tumor response and to depth of necrosis. In several cases tumors completely disappeared following HpD-PDT + CPI. The number of complete tumor responses was higher when PDT + 200 mg of CPI was used, i.e. 6 out of 10 rats. Promising results have also been obtained with regard to survival time of treated animals and to induction of tumor necrosis. We may presume that a combination of PDT and proteinase inhibitors could be a useful tool in further anticancer studies and, hopefully, in anticancer therapy.

Ki-67 reactivity in primary fallopian tube cancers.

Forty-four cases of primary cancer of the fallopian tube (PFTC) were analyzed as to Ki-67 expression, grade, stage and the cancer histological type. Among patients with an average age of 57.5 years (range 38-70 years), 27 patients were FIGO I, 7 were FIGO II and 10 were FIGO III. Histological classification of PFTC revealed 18 cases of endometrioid type, 9 serous, 7 undifferentiated, 6 urothelial, 2 clear-cell and 2 of other type. Histological grading revealed 11 cases of G1, 16 of G2 and 17 of G3 tumors. The quantity of Ki-67 positive cells was counted on 300 cancer cells in random high-power fields (10 x 40) and recorded as the labeling index (LI, %). Positive staining for Ki-67 was shown in the nuclei in all cases. Ki-67 LI values ranged from 14.2 to 97.2% (median 36.1). Ki-67 LI values were graded as > or = 36.1% as high and <36.1% as low. We did not find any significant differences in Ki-67 LI values among tumors of various clinical stages, histological grades and histological types. The p value was statistically significant only for stage as a prognostic factor.

New potent sensitizers for photodynamic therapy: 21-oxaporphyrin, 21-thiaporphyrin and 21,23-dithiaporphyrin induce extensive tumor necrosis.

New sensitizers for photodynamic therapy (PDT) are reported. These compounds, namely 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin, reveal some of the properties required for such therapy. Their physicochemical, chemical and pharmacological features meant that we could use them in the treatment of transplantable BFS1 fibrosarcoma in Balb/c mice. New sensitizers and the well-known chlorin e6 (Ce6) were used in doses of 2.5, 5.0, 7.5 and 10.0 mg/kg body weight, given intraperitoneally and followed by light irradiation, the total light doses being 50, 100 and 150 J/cm(2) within 24 h after injection. The effectiveness of new sensitizers in PDT was evaluated with in terms of tumor necrosis intensity, the survival time of treated animals, the rate of tumor response (complete/partial/no response), and skin photosensitivity. These results were compared to results obtained in analogous conditions after Ce6-PDT. Distribution studies revealed that the highest concentration of new compounds occurred within 24 h after injection. The results of these experiments confirmed that 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin can be considered as potent tumor photosensitizers that do not exert any unwanted effects, primarily skin photosensitization. We suggest that these porphyrins are possible sensitizers to be applied in clinical PDT.

Primary endometrioid carcinoma of fallopian tube. Clinicomorphologic study.

Twenty cases of primary Fallopian tube endometrioid carcinoma (PFTEC) are presented in the paper. This accounts for 42.5% of all histologic forms of primary Fallopian tube carcinoma (PFTC) found in our Department. The youngest patient was 38, and the oldest 68 years (mean: 56 years). Seven patients were nulliparas. Only two cases were bilateral. According to FIGO staging, 13 cases were evaluated as stage I, 4 as II, and 3 as stage III. Due to the histologic grading, 8 tumors were classified as well, 7 as moderately, and 5 as poorly differentiated. In the time of preparation of the manuscript, 12 women were still alive, 2 of them with recurrent disease. The follow-up of patients without recurrence ranged from 4 to 120 months (median: 63). Eight patients had died (survival time: from 4 to 65 months; median: 26). Metastases were found in 8 patients, especially to ovaries. In 14/20 cases of PFTEC various forms of tubal wall invasion were observed. Blood or lymphatic vessels involvement was found in 9 patients. Six of them had died and one is alive with the symptoms of disease. Immunohistochemical detection of the mutant form of p53 protein and oncogene product, c-erbB-2, was studied in 17 cases. Nine patients exhibited simultaneous p53 protein accumulation and c-erbB-2 expression. 2/9 of these patients are alive with recurrent tumors and 4/9 died. Endometrioid carcinoma of the Fallopian tube can be characterized by a tendency to superficial invasion of tubal wall and in a half of the cases by invasion of vessels. The majority of these tumors were diagnosed at an early stage tumors.

[Clinical applications of photodynamic therapy in the treatment of laryngeal lesions]. / Kliniczne zastosowanie fotodynamicznej terapii w leczeniu schorzen krtani.

Photodynamic therapy (PDT) has been used in the treatment of laryngeal lesions. The disorders comprised primary dysplasia and leukoplakia of the vocal cords. The patients after diagnosis were subjected to the therapy. Six hours prior to the light irradiation the patients received 4% solution of delta-aminolevulinic acid (ALA) during 30 minutes inhalation. After 6 hours all the changes were irradiated using 400 nm wavelength light from 300 W halogen lamp (range: 380-420 nm) in order to visualize them. Next, the wavelength was tuned to 650 nm (range 620-680 nm) and the total dose 120 J/cm2 for all cases. Control examinations in patients revealed complete response of the lesions within 2-3 months after PDT.

Tumor histopathology following new sensitizers: dithiaporphyrin- and sulfoxaporphyrin-mediated photodynamic therapy.

BACKGROUND: Our main aim was to evaluate tumor histopathology following new sensitizer-mediated photodynamic therapy (PDT). MATERIALS AND METHODS: In order to complete our studies we decided to use photosensitizers, i.e. dithiaporphyrin (DTP) and sulfoxaporphyrin (OXA) in combination with halogen lamp irradiation of presensitized tumors. The doses of sensitizers were: 2.5, 5.0, 7.5 and 10.0 mg/kg of body weight and total light doses were: 50, 100 and 150 J/sq.cm at the selected wavelength. Following such a treatment we have evaluated tumor necrosis of BFS1 fibrosarcoma growing on BALB/c mice. Together with tumor necrosis evaluation we have examined skin response to photodynamic treatment. RESULTS: We have found that both new sensitizers caused significant tumor damage at no skin alterations. The induction of tumor necrosis seemed to be dose dependent, i.e. higher photodynamic doses (sensitizer dose x light dose) resulted in more severe damage to the tumors than the lower doses. CONCLUSION: Our study showed that BFS1 fibrosarcoma is highly sensitive to PDT after application of new sensitizers. Both compounds can be considered as potent tumor photosensitizers in future clinical trials.

Photodynamic treatment of epithelial tissue derived from patients with endometrial cancer: a contribution to the role of laminin and epidermal growth factor receptor in photodynamic therapy.

Photodynamic therapy (PDT) was used to treat endometrial G1 cancer tissue derived from patients who had undergone a total hysterectomy and bilateral salpingo-oophorectomy. After surgical treatment the cancerous tissue was kept in a medium containing Dulbecco solution, fetal calf serum, and antibiotics. The tissue was then exposed to hematoporphyrin derivative (0.1 mg/ℓ) and 24 h later exposed to light (total light dose-18 J/sq cm). Necrosis depth was evaluated 24 h later using a light microscope. In order to assess the possible role of the basal membrane component laminin, as well as epidermal growth factor receptor susceptibility to PDT, immunohistochemical studies were carried out. Additionally, nucleolar organizer regions evaluation was performed. Our experiment confirmed that PDT results in the necrosis in the treated endometrial cancer, while not affecting the laminin in the cancerous tissue. In contrast, PDT strongly affects the epidermal growth factor receptor and nucleolar organizer regions in cancer cells. We suggest that laminin may contribute to the prevention of cancer dissemination in the cases where PDT has to be repeated, and that after PDT the cells become less susceptible to a mitogen, like, e.g., epidermal growth factor. © 1999 Society of Photo-Optical Instrumentation Engineers.

5-Aminolevulinic acid photodynamic therapy of transplantable colon adenocarcinoma in BALB/c mice.

We present results of preliminary studies on 5-aminolevulinic acid (5-ALA)-photodynamic therapy (PDT). In order to assess the effectiveness of 5-ALA-PDT we have used BALB/c mice transplanted subcutaneously with mouse colon adenocarcinoma C51. 5-ALA in the dose of 50 mg/kg was given intraperitoneally and 5 h later tumors were exposed to light at total doses from 50 to 75 J/cm2, wavelength 630+/-20 nm and light intensity 200 mW/cm2. Several time points following 5-ALA injections have been used to measure protoporphyrin IX (PpIX) concentration in different tissues from unirradiated mice. PDT effects were evaluated with regard to survival time, tumor response and necrosis depth. The main finding in our tumor model was that the optimum tumor to skin ratio of PpIX occurs within 5 h after sensitizer injection. 5-ALA-PDT resulted in prolongation of survival time of treated mice as compared to control animals and, in some cases, in complete response of tumors. PDT also caused increase in tumor necrosis, while no skin photodamage was observed.