Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons.

Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in the dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in the microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu(31), Pro(34)]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked the detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu(31), Pro(34)]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu(31), Pro(34)]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [(35)S]GTPγS binding simulated by [Leu(31), Pro(34)]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating the inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception.

Y1 receptor knockout increases nociception and prevents the anti-allodynic actions of NPY.

OBJECTIVE: Recent pharmacologic studies in our laboratory have suggested that the spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY. To rule out off-target effects, the present study used Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1 receptors to pain modulation. METHODS AND RESULTS: Y1(-/-) mice exhibited reduced latency in the hotplate test of acute pain and a longer-lasting heat allodynia in the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did not change CFA-induced inflammation. Upon targeting the spinal NPY systems with intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA model and the partial sciatic nerve ligation model of neuropathic pain. Importantly, we show for the first time that NPY does not exert these anti-allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice, concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti-allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the Rotorod test, arguing against an indirect effect of motor function. CONCLUSION: The Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY.

Validation of a single-day maximal lactate steady state assessment protocol.

AIM: The classical maximal lactate steady state (MLSS) assessment protocol takes multiple days to measure thus necessitates athletes to return to a laboratory for several visits. The purpose of this study was to assess the validity and reliability of a new protocol (Palmer protocol), which proposes to measure MLSS in a single-day. METHODS: Nine endurance-trained males (age 21.1 +/- 1.6 years, VO2max of 63.2 +/- 3.2 ml x kg(-1) x min(-1)) performed the Palmer protocol and the classical MLSS assessment protocol. The classical MLSS protocol consisted of several constant-velocity runs of increasing intensity. The MLSS was defined as the highest velocity associated with an increase in blood lactate concentration ([La-]) = or < 1.0 mmol x L (-1) during the final 20 min of a 30 min run. Concurrent validity was assessed by calculating a Pearson product correlation coefficient between the running velocity at MLSS from the classical protocol and from the single-day Palmer protocol. Test-retest reliability was assessed by calculating a Pearson product correlation coefficient between the running velocities from 2 separate trials of the single-day Palmer protocol. RESULTS: The velocity at MLSS from the single-day Palmer protocol (236.4 +/- 27.8 m x min(-1)) produced a strong correlation of 0.97 (p<0.001) with the velocity at MLSS from the classical protocol (226.3 +/- 22.6 m x min(-1)). An equally strong correlation was calculated from test-retest reliability of the single-day Palmer protocol (r=0.97), (p<0.001). CONCLUSION: These results suggest that the single-day Palmer protocol is valid and reliable in the estimation of MLSS.

The effects of supplemental carbohydrate ingestion on intermittent isokinetic leg exercise.

BACKGROUND: The purpose of this investigation was to examine the effects of carbohydrate (CHO) supplementation on isokinetic leg extension/flexion exercise performance, blood glucose responses, blood free fatty acid (FFA) responses, and blood lactate (La) responses. METHODS: Eight resistance trained males (mean+/-SEM, age: 23.7+/-1.3 yrs, height: 180.0+/-3.5 cm, bodymass: 94.9+/-4.9 kg) participated in a randomized, double blind protocol with testing sessions separated by 7-d. Subjects were given CHO or placebo (P) while performing 16 sets of 10 repetitions at 120 degrees x s(-1) on a Cybex isokinetic dynamometer. Performance variables measured were; total work (TW), average work (AW), peak torque (PT) and average torque (AT). Plasma glucose (PG), FFA, and La were measured prior to testing (PRE), after set 8 (MID), and 16 (POST). RESULTS: Results indicated that the CHO treatment elicited significantly (p<0.05) more TW (CHO: 41.1+/-3.9 kJ; P: 38.1+/-3.9 kJ) and AW (CHO: 2.6+/-0.2 kJ; P: 2.4+/-0.2 kJ). There were no differences (p<0.05) between treatments for PT of the hamstrings (CHO: 91.6+/-6.5 Nm; P: 87.4+/-8.5 Nm) and quadriceps (CHO: 129.7+/-9.5 Nm; P: 123.0+/-10.6 Nm). The AT of the hamstrings (CHO: 77.8+/-5.2 Nm; P: 75.7+/-8.7 Nm) and quadriceps (CHO: 116.9+/-8.9 Nm; P: 110.0+/-8.5 Nm) were not statistically different (p>0.05) between the treatments. PG was significantly higher at the POST blood draw in the CHO treatment. No significant differences (p>0.05) were observed between the treatments for FFA and La concentrations. CONCLUSIONS: The data from this investigation indicate that the use of CHO supplementation during isokinetic leg exercise allows for the performance of more work.

Carbohydrate supplementation attenuates muscle glycogen loss during acute bouts of resistance exercise.

The effects of carbohydrate (CHO) supplementation on muscle glycogen and resistance exercise performance were examined with eight highly resistance trained males (mean +/- SEM, age: 24.3 +/- 1.1 years, height: 171.9 +/- 2.0 cm, body mass: 85.7 +/- 3.5 kg; experience 9.9 +/- 2.0 years). Subjects participated in a randomized, double blind protocol with testing sessions separated by 7 days. Testing consisted of an initial isokinetic leg exercise before and after an isotonic resistance exercise (IRT) session consisting of 3 leg exercises lasting approximately 39 min. Subjects consumed a CHO (1.0 g CHO.kg body mass(-1)) or placebo treatment (PLC), prior to and every 10-min (0.5 g CHO.kg body mass(-1)) during the IRT. Muscle tissue was obtained from the m vastus lateralis after a supine rest (REST) immediately after the initial isokinetic test (POST-ISO) and immediately after the IRT (POST-IRT). The CHO treatment elicited significantly less muscle glycogen degradation from the POST-ISO to POST-IRT (126.9 +/- 6.5 to 109.7 +/- 7.1 mmol.kg wet weight(-1)) compared to PLC (121.4 +/- 8.1 to 88.3 +/- 6. 0 mmol.kg wet weight(-1)). There were no differences in isokinetic performance between the treatments. The results of this investigation indicate that the consumption of a CHO beverage can attenuate the decrease in muscle glycogen associated with isotonic resistance exercise but does not enhance the performance of isokinetic leg exercise.

[The dosage calculation of very small irregular electron irradiation fields. 2. The dosage distribution at the edge of the field]. / Dosisberechnung sehr kleiner irregulärer Elektronen-Bestrahlungsfelder. Teil 2: Dosisverteilung am Feldrand.

Cross beam dose distributions of the small square electron fields (1 x 1 to 6 x 6 cm2), used in the first part of this paper, have been measured at a linac equipped with metal diaphragms attached to a closed cone. They have been used for calculation of the mean square radial displacements sigma 2 of the corresponding pencil beams. Due to complicate electron scattering at the cone and the diaphragm, the pencil beam method could not be used with the simplicity and accuracy desired in practice. Therefore, the therapeutical sufficient field widths, field areas and integral doses have been determined directly from the measured dose distributions, and are represented in dependence from the geometric field size. For small fields we found considerable reductions of these values, which, in practice have to be compensated by enlargement of the geometric field size.

[Dose calculation for very small irregular electron beam fields. 1. Dose calculation for the central beam using a simple field zone method]. / Dosisberechnung sehr kleiner irregulärer Elektronen-Bestrahlungsfelder. 1. Teil: Dosisberechnung auf dem Zentralstrahl mit einer einfachen Feldzonenmethode.

Very small electron beams show considerable reduction of the dose output factor, the therapeutically relevant range, the practical range and the therapeutically relevant field size, compared to broad beams. The first three effects were measured on the central beam axis for different quadratic field sizes and are presented in the first part of this publication. A simple field zone method for calculation of irregular shaped electron beams was developed from the different depth dose curves. The method allows the determination of the maximum dose and the 80% range with sufficient accuracy for practical purposes. The examination of the reduction of the therapeutically relevant field size and the consequences following thereof with respect to the adequate electron therapy of a small irregular target volume will be published in a second part.

Gamma irradiation as a substitute for H2O2 in peroxidase-labelled enzyme immunoassays.

The ability of gamma irradiation to substitute for H2O2 in peroxidase-labelled enzyme immunoassays was investigated. Colouring of TMB (3,3',5,5'-tetramethylbenzidine), ABTS [2,2'-azino-di(3-ethylbenzthiazoline-6-sulphonic acid)], and OPD (o-phenylenediamine) was produced with doses of 10 and 20 Gy. Addition of superoxide dismutase enhanced TMB and ABTS, and inhibited OPD. The reaction was terminated when the irradiation was stopped. The use of denaturing compounds to stop the reaction was unnecessary and coated antigens could be re-used for a second immunoassay.

[Treatment of symptomatic mucinosis follicularis in mycosis fungoides using fast electrons]. / Behandlung einer symptomatischen Mucinosis follicularis bei Mycosis fungoides mit schnellen Elektronen.

Mucinosis follicularis is a chronic type of dermatosis involving the sebaceous glands and outer root sheaths, which can be differentiated into primary and secondary types. The latter - also called symptomatic mucinosis follicularis - causes therapeutic problems because of the underlying malignant lymphoma. Successful treatment using electron beams supported by etretinate is described in detail in a 40-year-old man with symptomatic mucinosis follicularis based on plaque-type mycosis fungoides. After 6 months free of skin symptoms, the mycosis fungoides lesions recurred in the overlapping borders of the irradiation fields. These lesions were treated again with electron beams. A relapse after 32 months was controlled by PUVA. Electron beam therapy is recomended in the plaque type of mycosis fungoides, especially if PUVA has no effect for some reason.

Total body irradiations at the University Hospital of Freiburg.

Since 1974, 65 patients have been treated with high dose total body irradiation before bone marrow transplantation. The irradiation technique is described using a 6 MeV-linear accelerator in a small treatment room.

Dosimetric problems associated with total body irradiation.

Total body irradiation (TBI), which is carried out with high energy photons at large source distances and with large fixed fields, involves special dosimetric requirements. The dose measurements published thus far on anthropomorphic phantoms have shown that deviations from the dose values calculated with "normal" dose functions occur as a result of completely different scatter radiation distributions. The higher the photon energy selected, the more slight these deviations become.

[Dose rate constant and radial dose function of an iodine 125 radiation source in various substances]. / Dosisleistungskonstante und radiale Dosisfunktion einer Jod-125-Strahlenquelle in verschiedenen Stoffen.

The dose distribution around an isotropic, point radiation source can be expressed by the dose rate constant, the quadratic law of distance, and a radial dose function which depends on the absorption and scatter processes occurring in the surrounding material. The radial dose function and the dose rate constant of a point iodine-125 source can be represented in a clear and rather exact manner as simple functions of the linear attenuation and energy absorption coefficients, because the average photon energy does not considerably vary with the growing distance from the source. This representation is in contrast with some functions defined in a distance of 1 cm, in conformity with the definition of the dose rate constant in the air according to DIN 6814, part 3.

Interstitial radiotherapy with 198Au seeds in the primary management of carcinoma of the oral tongue: results in Freiburg/Breisgau from January 1964 to July 1980.

Thirty-two patients with histologically proven carcinoma of the oral tongue, Stage T1-3, were analyzed retrospectively. They were treated from January 1964 through July 1980 in Freiburg by interstitial implantation with Au-198-seeds for the primary tumor management. Out of 25 patients with complete follow-up, one patient developed a local recurrence. In three patients, regional lymph node metastases occurred, once after prior adjuvant radiotherapy to the regional lymph nodes area, and in two patients after exclusive interstitial radiotherapy to the tumor of the tongue. The overall five-year survival rate was 52% for all stages (overall group), 75% for Stage T1 and 44% for Stages T2-3. The corrected five-year survival rate was 75% for all stages, 86% for Stage T1 and 71% for Stages T2-3. The method of 198Au-seed implantation as it is practiced in Freiburg is discussed, as well as the radiation exposure of the personnel.

5 years of operation experience with a 4 MeV linear accelerator in radiotherapy.

The results of our experience in operating a 4 MeV linear accelerator Clinac 4 from Varian in radiotherapy are reported, especially considering the 12-hours-per-day operation for more than the last 3 years. Frequency of defects of different parts is discussed. The downtime adds up to 6 days per year, service and repair costs amount of US $ 33,--per patient.

[First report of experiences with interstitial radiation therapy of the prostatic carcinoma using 125-I-seeds: indication, practical performance and radioprotection (author's transl)]. / Erster Erfahrungsbericht über die interstitielle Strahlentherapie des Prostatakarzinoms mit 125-Jod-Kapseln. Indikation, praktische Durchführung und Strahlenschutz.

The practical and organizing performance of interstitial radiation therapy with 125-I-seeds in prostatic carcinoma is reported. Precautions and measurements for radioprotection are emphasized. First evaluations of these measurements show that this therapeutical technique can be performed in complete accordance with the directive for radioprotection. The computer-assisted isodose-planning and the in-vivo-measurements in the rectum, urethra and bladder confirm the steep decrease of the dose outside the irradiated focal volume. Hence, inflammatory symptoms accompanying the therapy are markedly allayed in comparison with percutaneous radiation therapy, in spite of a higher tumor dose. Because of the extensive operation, attention must be paid to the strict observation of indication criteria.

[Present state of the wide-field megavoltage radiotherapy of Hodgkin's disease. Fundamentals, performance, side effects (author's transl)]. / Gegenwärtiger Stand der Grossfeldtechnik unter Megavoltbedingungen bei der Strahlentherapie der Hodgkin'schen Erkrankung. Grundlagen, Durchführung, Nebenwirkungen.

Therapeutic results of Hodgkin's disease could be significantly improved by the introduction of megavoltage radiotherapy equipment and more profound knowledge about this disease. By this way, five year survival rates of 70% can be achieved for all stages and up to 100% for the early stages. The wide field technique enables the coverage of all lymph nodes with protection of non involved organs. Simultaneously, these improved technical conditions make optimal radiation planning necessary which demands numerous technical auxiliaries. Radiation type and radiation energy are important preconditions for the therapy; production and usage of shilding blocks are necessary for individual performance. The principle for optimal radiation dose distribution are measurements and calculations on the phantom which are now included in computer programs. Nevertheless, radiation of large volumes represent a high stress for the patient. Despite the improvement of the therapeutic results there are except the acute radiation side effects, also irreversible alterations. These can be analysed only after long time observations and has to be balanced with the therapeutic results. The knowledge of these side effects is very important for the radiologist. Beside that, the risk of induction of a second tumor has to be considered. The present possibilities of absolute control of this disease enables the overtreatment of lesions in the early stages. Therefore it has to be postulated to regard the present therapy concepts with attention and to consider the possible side effects.