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The decennial Census survey marks the emergence of federal classifications of race and ethnicity by which the U.S. government has historically conflated Native Hawaiians and Pacific Islanders (NHPI, hereafter) as "Asian or Pacific Islander." This conflation amplifies health injustices and inequities of NHPIs through multiple mechanisms because it masks the complex and heterogeneous experiences of NHPIs, whose positions and relations with the settler state are qualitatively and substantially distinct from Asian Americans. This critical review examines federal documents and research to examine how the panethnic categorizations are often sustained through scientific inquiry and methodologies. We found that self-determination and self-identification for NHPIs are impeded by settler-colonial relations between U.S. colonization of parts of Oceania (e.g., Hawai'i, Sāmoa, Fiji, and Guam) and the forcefully imposed categorization that continues to be in use to legitimize the domination of Indigenous Peoples through race misclassification. Specifically, Census data collection fails to capture accurate and reliable data due to serious methodological limitations. These implications for psychological research compel us to make several recommendations for psychologists: (1) engage with NHPI community partners in all research processes; (2) critically examine Census research design and consider oversampling NHPI households to ensure just data representation; (3) meaningfully engage when, whether and how to aggregate Asian Americans with NHPIs; and (4) use Indigeneity as a critical framework.

The paper presents a numerical simulation of two-phase turbulent flow in straight horizontal channels of pneumatic transport with non-circular cross-section. For the granular flow simulation, we have chosen the flow of solid particles of quartz, flour, and ash in the flow of air, which is transporting fluid. During the modeling of the flow, the transported solid particles are reduced to spherical shapes. A correction of the stress model of turbulence is performed by taking into account the influences of the induction of secondary flows of the second order in the gas phase. The full Reynolds stress model was used for modeling the turbulence, and the complete model is used for the turbulent stresses and turbulent temperature fluxes. All numerical experiments were conducted for the same initial flow conditions and a single uniform grid was adopted for all numerical experiments. The flow is observed in a straight channel of a square cross-section and dimensions of sides of 200 mm and the length of 80 Dh. During the simulation, the fineness of the numerical grid was also tested, and the paper shows results of the numerical grid of the highest resolution beyond which the fineness does not influence the obtained results. The paper offers graphics of velocities of the solid particles transported by the transporting fluid (air) along the channel.

Activities related to buildings contribute to a large degree to environmental degradation. It is necessary to reduce the negative environmental impact and resource consumption throughout the life cycle of the building. The aim is to optimize building performances in accordance with the integrated design objectives. The building structure, along with other elements of architectural space, deter-mines the performances of the building. The building structure should be designed and evaluated as a sub-system of the building, whose behaviour is directed towards the aim of system-building ? ecological quality. This paper deals with the analysis of structural design in accordance with integrated design objectives, which are derived from quantitative and qualitative indicators of ecological quality of building, within the criteria of environmental protection throughout the life cycle of the building. The overall objective is to reduce harmful emissions to the air, water and soil, as well as to increase the efficiency of resource use, that is, to reduce the intensity of their use. Based on subject analysis, the environmentally-based criteria for the design and evaluation of building structures are derived, in the function of creating the environmentally acceptable building solutions. The present analysis points to the necessity of applying a complex and systemic approach to structural design, in function of achieving the ecological quality of buildings.

Extensive research has been carried out with regard to the composition of the exhaust gases of Diesel engines in operation with biodiesel in relation to the operation with the conventional diesel fuel. Producing biodiesel from different raw materials and different technological biodiesel production processes can result in different individual physical and chemical characteristics of fuel. Generally, it can be said that the use of biodiesel (and mixtures) reduces the overall toxicity of the exhaust gases in relation to the operation of the engine with diesel fuel, and this is a significant environmental potential of biodiesel as a fuel for Diesel engines. However, there is a diversity of research results, due to different factors. The paper reviews and summarizes the relevant literature on the mentioned research that can contribute to the explanation of these effects. It also points to the need for a very careful selection of biodiesel for use as a Diesel engine fuel.

The paper considers two-phase gas-solid turbulent flow of pneumatic transport in straight horizontal channels with a non-circular cross-section. During turbulent flow, a specific flow phenomenon, known as secondary flow, occurs in these channels in the cross-sectional plane. The existence of strong temperature gradients in the cross-sectional plane of the channel or the cases of curved channels result in the appearance of the secondary flow of the first kind. However, in straight channels with a non-circular cross-section, in the developed turbulent flow mode, a secondary flow, known as Prandtl?s secondary flow of the second kind, is induced. The paper presents a numerical simulation of a developed two-phase turbulent flow by using the PHOENICS 3.3.1 software package. Reynolds stress model was used to model the turbulence. The paper provides the data on the changes in turbulent stresses in the channel cross-section as well as the velocities of solid particles transported along the channel.

The paper presents the results of a technical and economic analysis of three stand-alone hybrid power systems based on renewable energy sources which supply a specific group of low-power consumers. This particular case includes measuring sensors and obstacle lights on a meteorological mast for wind measurements requiring an uninterrupted power supply in cold climate conditions. Although these low-power (100 W) measuring sensors and obstacle lights use little energy, their energy consumption is not the same as the available solar energy obtained on a daily or seasonal basis. In the paper, complementarity of renewable energy sources was analysed, as well as one of short-term lead-acid battery-based storage and seasonal, hydrogen-based (electrolyser, H2 tank, and fuel cells) storage. These relatively complex power systems were proposed earlier for high-power consumers only, while this study specifically highlights the role of the hydrogen system for supplying low-power consumers. The analysis employed a numerical simulation method using the HOMER software tool. The results of the analysis suggest that solar and wind-solar systems, which involve meteorological conditions as referred to in this paper, include a relatively large number of lead-acid batteries. Additionally, the analysis suggests that the use of hydrogen power systems for supplying low power-consumers is entirely justifiable, as it significantly reduces the number of batteries (two at minimum in this particular case). It was shown that the increase in costs induced by the hydrogen system is acceptable.

The mixed forest of fir, spruce, and beech (Piceo-Abietetum Colic 1965) is an important and widespread plant community on the Balkan Peninsula. Within the Dinarides, it occupies the upper zone of the beech-fir forest belt, establishing a regional belt of vegetation in the Illyrian province. This community occupies significant areas in western and southwestern Serbia where it also creates a regional belt, thus confirming that this part of Serbia belongs to the Illyrian floral-geographical province. This paper compares the floristic composition of the fir-spruce-beech forests in Serbia and Bosnia-Herzegovina in order to determine the differences between the study stands. A total of 29 releves were analyzed, 17 from the mountain of Lisina (Bosnia-Herzegovina) and 12 from the Pester plateau (Serbia). Cluster analysis revealed a clear differentiation between the study stands and species in Bosnia-Herzegovina and those in Serbia. The main difference is in the dominant species: Fagus moesiaca (K. Maly) Czecz. in Serbia and Fagus sylvatica L. in Bosnia-Herzegovina. In Bosnia-Herzegovina, the forest grows under conditions of a uniform, maritime and humid climate, while in Serbia it grows under conditions of a continental climate with less rainfall and a strong zoo-anthropogenic impact. Regarding the spectrum of life forms, there are more phanerophytes and geophytes in Bosnia-Herzegovina than in Serbia. On the other hand, the spectrum of floral elements in Serbia is richer in xerophilous, Balkan and sub-Mediterranean floral elements.

Stress calculation of steam pipeline is presented, focused on the welded joint. Numerical calculation was performed using the finite element method to obtain stress distribution in the welded joint made while replacing the valve chamber. Dissimilar materials were used, namely steel 10CrMoV9-10 according to EN 10216-2 for the valve chamber, the rest of steam pipeline was steel X20, whereas the transition piece material was steel X22. Residual stresses were calculated, in addition to design stresses, indicating critical regions and necessity for post-weld heat treatment.

A miniature inertial sensor placed on fingertip of index finger while performing finger tapping test can be used for an objective quantification of finger tapping motion. Temporal and spatial parameters such as cadence, tapping duration, and tapping angle can be extracted for detailed analysis. However, the mentioned parameters, although intuitive and simple to interpret, do not always provide all the necessary information regarding the subject?s motor performance. Analysis of frequency content of the finger tapping movement can provide crucial information about the patient's condition. In this paper, we present parameters extracted from spectral analysis that we found to be significant for finger tapping assessment. With these parameters, tapping?s intra-variability, movement smoothness and anomalies that may occur within the tapping performance can be detected and described, providing significant information for further diagnostics and monitoring progress of the disease or response to therapy.

Traminer is a well-known grapevine cultivar. It is thought to originate from Tramin, Italy, wherefrom it has been introduced to many European countries (France, Switzerland, Austria, Germany). Researches included two Traminer cultivar forms: White Traminer and Red Traminer. Examinations were carried out in a collection vineyard of the Viticulture and Wine Production Center of Nis. The collection vineyard was planted in 1995, with planting space of 3 x 1.2 m. Examinations took three years (2004-2006) and encompassed phenological observations, fertility, vegetative potential of a vine, resistance to Botrytis cinerea and wine quality. A detailed ampelographic description of two Traminer cultivar forms was also provided according to O.I.V. descriptors. The purpose of this paper is to determine growth, fertility, yield, and grape and wine quality of the examined Traminer cultivar forms in the viticultural subregion of Nis. According to the results obtained, the examined forms could be successfully grown in this region. Average grape yield varied depending on conditions of the particular year. White Traminer recorded higher yield, while Red Traminer recorded better quality. In addition, the best vines have been selected within the forms, and they will be used in further studies and multiplication.

The paper presents the design and operating characteristics of a model of reversible axial fan with only one impeller, whose reversibility is achieved by changing the direction of rotation. The fan is designed for the purpose of providing alternating air circulation in wood dryers in order to reduce the consumption of electricity for the fan and increase energy efficiency of the entire dryer. To satisfy the reversibility of flow, the shape of the blade profile is symmetrical along the longitudinal and transversal axes of the profile. The fan is designed with equal specific work of all elementary stages, using the method of lift forces. The impeller blades have straight mean line profiles. The shape of the blade profile was adopted after the numerical simulations were carried out and high efficiency was achieved. Based on the calculation and conducted numerical simulations, a physical model of the fan was created and tested on a standard test rig, with air loading at the suction side of the fan. The operating characteristics are shown for different blade angles. The obtained maximum efficiency was around 0.65, which represents a rather high value for axial fans with straight profile blades.

The motivation for this study is the disagreement of statistical and literature data about potential quantities of biomass in Serbia. This difference is mainly caused by changed status in practice due to several reasons: changes in ownership caused by transition, different application of technologies in practices, organization of work and economic reasons. The main aim is to precisely establish sorts and amounts of organic biomass in Serbia that can be transformed into heat and electricity. So far, data about the quantities of biomass residues in agriculture, forestry and communal services have been collected and published. Data collection methods are different and generally based on statistical data. The paper explains in detail methods of data collection and processing of crop production, fruit growing and viticulture, livestock, forestry and communal services. On the basis of precise data collection, it has been established that there are 26.3 million tons of biomass residue in Serbia every year. The total amount of biomass is reduced by 20-30% in relation to the period of 10 and more years ago. On the basis of the situation in agriculture and forest production in Serbia, it is estimated that out of the total amount of biomass, some 30-40% can be used for the production of heat energy, electricity and biofuel. The remaining biomass can be used in order to increase soil fertility, as cattle spread, for vegetable production, means for polishing in metal industry, for insulation in civil engineering, in cosmetics industry, production of animal feed, and so on.

Cholinergic receptors of parasitic nematodes are one of the most important possible sites of action of antiparasitic drugs. This paper presents some of our own results of electrophysiological and pharamcological examinations of nicotinic and muscarinic receptors of nematodes, as well as data from literature on a new class of anthelmintics that act precisely on cholinergic receptors. The nicotinic acetylcholine receptor (nAChR) is located on somatic muscle cells of nematodes and it is responsible for the coordination of parasite movement. Cholinomimetic anthelmintics act on this receptor, as well as acetylcholine, an endogenic neurotransmitter, but they are not sensitive to enzyme acetylcholineesterase which dissolves acetylcholine. As opposed to the nicotinic receptor of vertebra, whose structure has been examined thoroughly, the stoichiometry of the nicotinic receptor of nematodes is not completely known. However, on the grounds of knowledge acquired so far, a model has been constructed recently of the potential composition of a type of nematodes nicotinic receptor, as the site of action of anthelmintics. Based on earlier investigations, it is supposed that a conventional muscarinic receptor exists in nematodes as well, so that it can also be a new pharamocological target for the development of antinematode drugs. The latest class of synthesized anthelmintics, named aminoacetonitriles (AAD), act via the nicotinic receptor. Monepantel is the first drug from the AAD group as a most significant candidate for registration in veterinary medicine. Even though several groups of cholinomimetic anthelmintics (imiodazothiazoles, tetrahydropyrimidines, organophosphat anthelmintics) have been in use in veterinary practice for many years now, it is evident that cholinergic receptors of nematodes still present an attractive place in the examinations and development of new antinematode drugs. .

Mushrooms like Ganoderma lucidum have been used for thousands of years as a traditional medicine in the Far East. Ganoderma received wide popularity as an eating mushroom with high nutritive value, but even more as medical fungi. It has been used for the treatment of various diseases: hepatitis, hypertension, insomnia, and even cancer. Due to its extraordinary action, it is often called 'Elixir of life', 'Food of gods' and 'Mushroom of universe'. The intracellular and extracellular polysaccharides (b-glucane) inhibit the growth of several types of cancer. Mushroom produces triterpenes of which especially ganoderic acid showed cytotoxicity on primary tumor liver cells, inhibition of histamine release, hepatoprotective effect, stimulation of the immune system functions, inhibition of the aggregation of blood plates, etc. On the other hand, beer as a purely natural beverage obtained in the process of fermentation, contains a number of ingredients which are important for human organism, and in moderate usage has favorable reaction on the general health condition of the body. As such, beer is a very good basis for the development of a number of new products with defined pharmacodynamics influence. In this work, we have investigated the possibilities of using extracts of mushroom Ganoderma lucidum in the production of special beer types. The composition of mushroom, properties of the most important active ingredients, extraction procedures, and sensory characteristics of the beers on the basis of such extracts were determined. The most important parameters of quality and possibility of adjustments using extracts of different medicinal herbs were investigated. Gljive poput Ganoderma lucidum korišćene su hiljadama godina u tradicionalnoj narodnoj medicini Dalekog istoka. Svoju veliku popularnost Ganoderma je stekla kao jestiva gljiva sa visokom nutritivnom vrednošću, ali još više kao medicinska gljiva. Korišćena je za lečenje raznih bolesti, između ostalih i hepatitisa, hipertenzije, insomnije, pa i karcinoma. Upravo zbog svog izvanrednog delovanja nazivana je 'Eliksir života', 'Hrana bogova', 'Gljiva univerzuma'. Njeni intracelularni i ekstracelularni polisaharidi (b-glukani) dokazano inhibiraju rast nekoliko vrsta karcinoma, a triterpeni koje produkuje, posebno ganoderinska kiselina, pokazuju citotoksičnost na primarne tumorne ćelije jetre, inhibiciju oslobađanja histamina, hepatoprotektivni efekat, stimulaciju funkcije imunog sistema, inhibiciju agregacije krvnih pločica itd. Sa druge strane, pivo kao potpuno prirodno piće dobijeno fermentacijom, sadrži mnogobrojne sastojke od značaja za organizam i u umerenoj količini pokazuje povoljno delovanje na opšte zdravstveno stanje organizma. Kao takvo, pivo je veoma dobra podloga za razvoj niza novih proizvoda definisanog farmakodinamičkog delovanja. U radu je ispitana mogućnost korišćenja ekstrakata gljive Ganoderma lucidum u proizvodnji specijalnih piva. Dati su sastav gljive, svojstva najvažnijih aktivnih sastojaka, postupci ekstrakcije i senzorne karakteristike piva dobijenih na bazi datih ekstrakata. Ispitani su najvažniji parametri kvaliteta i mogućnost korigovanja upotrebom ekstrakata različitog lekovitog bilja.

Economic, social and expert-scientific factors determine activities in connection with the development of the control of parasitic infections in the upcoming period of the 21st century. The primary research activities are directed at studies of the physiological functions of parasites and the ecological relations between the parasite and the host, and all that is undertaken with the objective of securing adequate pharmacotherapy/pharmacoprophylaxis and immunoprophilaxis. As there is a huge expansion in the synthesis of chemical compounds, there is a great number of potential substances for use in the form of a medicine. Along these lines, activities concerning the development of new antiparasitics and/or modification of existing ones are primarily based on securing a quality target spot for its action. Another possibility in the area of research is connected to the problem of resistance of parasites and intensive studies of the biochemical-physiological characteristics of parasites, as well as the development of an active epidemiological-episootiological network for monitoring resistance. In parallel with the development of medicines, the results of investigations of physiological functions of parasites and their mutual relations with their host, are intensely used for the development of immunological control, and the development of vaccines (for example, the development of vaccines for the control of coccidiosis, babesiosis, echinococcosis). The second important approach is related to studies of parasitic zoonoses, the effect of global warming on the epidemiological-episootiological characteristics of parasitic diseases and the selection of resistant animal breeds/hybrids. Animal welfare is also of importance, the perfecting of reliable, rapid and less-costly methods for diagnosing parasitic diseases and the development of in vitro methods for the examination of resistance to antiparasitics. Ekonomski, socijalni i stručno-naučni faktori uslovljavaju aktivnosti vezane za razvoj kontrole parazitskih infekcija, u predstojećem periodu 21.veka. Primarne istraživačke aktivnosti usmerene su ka izučavanju fizioloških funkcija parazita i ekološkog odnosa parazit domaćin, a sve u cilju obezbeđenja adekvatne farmakoterapije/farmakoprofilakse i imunoprofilakse. Kako je sinteza hemijskih jedinjenja u ogromnoj ekspanziji, postoji veliki broj potencijalnih supstanci za primenu u vidu leka. U skladu sa time, i aktivnosti razvoja novih antiparazitika i/ili modifikacije postojećih se zasnivaju prvenstveno na 'obezbeđivanju' kvalitetnog ciljnog mesta delovanja. Druga mogućnost na istraživačkom planu je vezana za problem rezistencije parazita i intenzivno izučavanje biohemijsko-fizioloških karakteristika parazita, kao i razvijanje aktivne epidemiološko epizootiološke mreže za praćenje rezistencije. Paralelno sa razvojem lekova, rezultati ispitivanja fizioloških funkcija parazita i njihovog međusobnog odnosa sa domaćinom, intenzivno se koriste za razvoj imunološke kontrole, odnosno razvoj vakcina (na primer, razvoj vakcina za kontrolu kokcidioze, babezioze, ehinokokoze i sl.). Drugi važan pristup je proučavanje parazitskih zoonoza, uticaja globalnog zagrevanja na epidemiološko-epizootiološke karakteristike parazitskih bolesti i selekcije otpornijih rasa/hibrida životinja. Od značaja je i dobrobit životinja, usavršavanje pouzdanih, brzih i jeftinih metoda za dijagnostikovanje parazitskih bolesti i razvoj in vitro metoda za ispitivanje rezistencije na antiparazitike.

Stomach diseases have an important place in the clinical pathology of dogs. Etiological factors can be nutritive, chemical, or infective, but treatment implies certain common general principles and a certain number of therapy protocols which are most often used. On the other hand, a part of the medicines used in the pharmacotherapy of stomach diseases in dogs are taken from the palette of medicines intended for human use, so that a regular dosage and regime of implementation are the main precondition for the success of the applied therapy. Drugs used in the treatment of stomach diseases include antiemetics, prokinetics, antacids, mucoprotectives, anticholinergics, H2-antagonists, proton pump inhibitors, semisynthetic derivatives of prostaglandin E1, and others. The therapy of stomach diseases implies the simultaneous application of several drugs from different pharmacodynamic groups (for instance, an antiemetic, a prokinetic, an antacid, and an Hg antagonist or a proton pump inhibitor) when it is necessary to establish a correct regime of implementation because of possible interaction, which will also be discussed in this work. Oboljenja želuca zauzimaju značajno mesto u kliničkoj patologiji pasa. Etiološki faktori mogu da budu nutritivni, hemijski ili infektivni, ali lečenje podrazumeva neke zajedničke opšte principe i određeni broj terapijskih protokola koji se najčešće primenjuju. Sa druge strane, jedan deo lekova koji se koriste u farmakoterapiji oboljenja želuca pasa preuzima se iz palete lekova namenjenih humanoj medicini, pa su pravilno doziranje i režim primene osnovni preduslov za uspeh terapije. Od lekova se u lečenju oboljenja želuca koriste antiemetici, prokinetici, antacidi, mukoprotektivi, antiholinergici, H2-antagonisti, inhibitor, protonske pumpe, polusintetski derivati prostanglandina E1 i drugi. Terapija oboljenja želuca podrazumeva istovremenu aplikaciju nekoliko lekova različitih framakodinamskih grupa (recimo antiemetik, prokinetik, antacid i H2 antagonista ili inhibitor protonske pumpe), kada je zbog moguće interakcije neophodno da se uspostavi pravilan rezim primene o čemu ćemo, takođe, govoriti u ovom radu.

We examined the effect of 20-hydroxyecdysone (20-HE), a neurosteroid found in insects that is involved in their developmental process, on both tonic convulsion and absence-like seizure in spontaneously epileptic rat (SER). When 20-HE was given orally to SER at 25-200 mg/kg, significant decreases of the tonic convulsion were observed with 100 and 200 mg/kg. Pretreatment of the animal with bicuculline (1 mg/kg, i.p.) antagonized the inhibitory effects of 20-HE. However, absence-like seizures were not affected by 20-HE. These findings indicate that 20-HE produces antiepileptic effects on tonic convulsion by acting on the modulatory site of GABA(A) receptors.

Spontaneously epileptic rats (SER), which represent a double mutation (zi/zi, tm/tm), spontaneously exhibit both tonic and absence-like seizures. We examine the long-term effects of a thyrotropin-releasing hormone (TRH) analogue, CNK-602A, acute administration of which was effective inhibiting both types of seizures in SER, to determine if this agent could be used to treat epilepsy for long periods. Food pellets containing 0.001% CNK-602A were given ad libitum to SER from age 7 weeks. CNK-602A significantly inhibited tonic convulsions and prolonged survival. There were no alterations in body weight or plasma levels of triiodotHyronine (T3) and thyroxine (T4). These findings indicate that chronic intake of CNK-602A in a dose that does not affect plasma levels of T3 and T4 inhibits tonic convulsions in SER and suggest that this drug may be an effective treatment for convulsive seizures in patients with epilepsy.

The effects of topiramate, a novel antiepileptic drug, on tonic and absence-like seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) and on sound-induced seizures in DBA/2 mice were investigated. Topiramate (20 and 40 mg/kg i.p.) inhibited both tonic and absence-like seizures in a dose-dependent manner, whereas phenytoin (20 mg/kg i.p.) and zonisamide (40 mg/kg i.p.) inhibited only the tonic seizures. The inhibitory effects of topiramate on absence-like seizures were antagonized by pretreatment with haloperidol (0.5 mg/kg i.p.), but those on the tonic seizures remained unaffected. Topiramate inhibited sound-induced seizures in DBA/2 mice (ED50 = 8.6 mg/kg p.o.). These findings suggest that topiramate may be effective for treatment of both convulsive and absence seizures of human epilepsy. The inhibitory effect of topiramate on absence-like seizures in SER may be mediated through the central dopaminergic system.

To achieve an ultra low flying height, a multi-functional PFPE lubricant was synthesized. The molecule was achieved by combining several PFPE unit molecules. The novel lubricant contains extra polar functional-groups in the middle of the molecule. These functional-groups enhance the lubricant and substrate interaction, which results in reduction of the lubricant monolayer thickness. Through this molecular designing, we were able to reduce the monolayer thickness by 30% compared with the commercially available lubricants. The reduction of lubricant monolayer thickness would provide an ultra low flying height.

Effects of 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine D3-receptor agonist, on neuronal activities of the nucleus accumbens (Acc) were examined in chloral hydrate-anesthetized rats. Spikes elicited by stimulation of the parafascicular nucleus were dose-dependently inhibited by microiontophoretic application of dopamine and 7-OH-DPAT. Glutamate-induced firing was also inhibited by these drugs. These findings suggest that D3 receptors are also involved in the postsynaptic inhibition of Acc neuron by dopamine.

This review article focused on the primary neurotransmitters involved in transmission from the otolith to the vestibular nucleus (VN), especially in relation to the neurotransmission to the VN neurons (gravity-sensitive neurons) activated by tilt stimulation. The medial vestibular nucleus (MVN) neurons were classified in 8 types (alpha-theta) according to the patterns in response to the clockwise and counterclockwise tilt-stimulations. The tilt-induced firing was inhibited by GDEE (a non-selective glutamate receptor antagonist) and/or atropine (a muscarinic receptor antagonist). Thus, glutamate and/or acetylcholine may serve as the primary neurotransmitters. This conclusion is supported by the previous findings that glutamate exists in the vestibular nerve and is released from the nerve besides the presence of glutamate receptor subtypes in the VN. In addition, acetylcholine induced atropine-reversible firing of MVN neurons, and the enzymes involved in acetylcholine synthesis/metabolism are also found in the VN. Furthermore, serotonin was found to inhibit the MVN neuronal activities via the 5-HT1A receptors. As such, the 5-HT1A agonist, tandospirone, may be effective in preventing and/or treating motion sickness and/or space sickness.

Monoamine transporters include plasma membrane and vesicular monoamine transporters(VMAT). The former selectively and Na+/Cl(-)-dependently transport dopamine, noradrenaline and serotonin into the cytoplasma, and the latter non-selectively carries monoamine into the vesicle. These transporters are composed of amino acid groups containing 12 folds more transmembrane components. Cytoplasmic transporters are a target site of certain drugs. Antiepileptic drugs such as SSRI and tricyclic antidepressants bind with serotonin transporter(SERT), noradrenaline transporter(NET) and/or dopamine transporters(DAT) to inhibit transport of monoamines into the cytoplasma, thereby increasing monoamine levels within the synaptic cleft. However, amphetamine, known to induce drug dependence, is transported by DAT and inhibit VMAT to induce reverse-transport of monoamines into the synaptic area, thereby producing psychiatric and behavioral alterations. Thus, monoamine transporters are target sites of drugs, and functional changes in the transporters may be involved in the pathogenesis of affective diseases, schizophrenia and/or personality disorders including neurogenerative diseases such as Parkinson's disease.

The effectiveness of mammographic screening in women aged over 50 years has been confirmed in the United States and Europe, but its effectiveness in women aged from 40 to 49 years remains controversial. The optimum age for effective screening of subjects for breast cancer by mammography in Japan was studied based on the results of mammographic screening.The benefit of breast cancer screening in women was examined by stratifying the results of mammographic screening in a Tokushima trial on the basis of age: under 50 years and 50 years or older. The results of conventional screening by physical examination alone, which we performed in a Zentsuji trial, were used as the control.The examinees numbered 13,982 and 18,619 in mammographic screening and screening by physical examination, respectively. Breast cancer was detected in 43 and 22 patients, respectively. The detection rate of breast cancer was 0.31% by mammographic screening, which is about 3 times higher than that (0.12%) by screening using physical examination. Mammographic screening thus showed significantly higher sensitivity (93.5% vs 73.3%, p = 0.015). The proportion of stage I cancer and the absence of nodal involvement were 67.4% and 79.1% by mammographic screening, compared with 31.8% and 59% by physical examination. Our results obtained with mammographic screening were equal to or higher than the results obtained in the United States and Europe. The clinical stage of the breast cancers detected by mammographic screening in the subjects aged under 50 years was stage 0 (DCIS) in one case and stage I in 10 cases, while the group aged 50 years or older showed stage 0 in 11 cases and stage I in 19 cases. There were three cases of false-negative; two false-negative cases were aged under 50 year, while one case was aged 50 years or older. The detection rates of cancer in the group under 50 years and that of 50 years or more were 0.19% and 0.39% by mammograpic screening and 0.09% and 0.15% by the physical examination. The sensitivities in the group under 50 years and that of 50 years or more were 84.6% and 97.0% by mammographic screening and 72.7% and 73.7% by physical examination, showing no significant difference. In the results of mammograms by Wolfe's classification with respect to the age groups, the proportion of DY (dense breast) pattern decreased significantly from 3.5% to 0.2% in women of 50 years or more and from 16.6% to 2.4% in those under 50 years when the values were compared between the period from 1992 to 1995 and the period from 1998 to 1999, respectively (p0.0001).The above findings suggested the possible effectiveness of mammographic screening not only in women aged 50 years or more but also in those aged under 50 years, in Japan. Therefore, introduction of mammography should be considered at an early date, even for women aged from 40 to 49 years.

The relationship between human papillomavirus (HPV) infection and breast cancer is controversial. In this study, paraffin-embedded tissue blocks prepared from 72 patients with benign, premalignant or malignant mammary lesions were randomly collected from the Shanghai region of China and Tokushima in Japan. DNA specimens extracted from all tissues were amplified by the polymerase chain reaction (PCR) using HPV16, 18 and 33 primers. Southern blot hybridization showed 19 cases to be positive for HPV33 DNA: The positive rate for HPV33 DNA in Chinese (41.7%) was significantly higher than in Japanese (11.1%) (P0.01): The positive rate for HPV33 DNA in invasive ductal carcinoma (34.1%) was higher than in benign or borderline mammary lesions (5%) (P0.02). There were no statistically significant difference among the relationship of the nuclear grade of breast cancers with HPV33 DNA-positivity. This is the first report of a positive correlation between HPV33 DNA and breast lesions in Chinese and Japanese populations. These results suggest that the infection by HPV33, but not HPV 16 or HPV 18, may be involved in breast hyperplastic lesions, especially breast cancer, in humans.

Fine needle aspiration (FNA) samples were obtained from 176 breast tumors suspected of malignancy, which were then subjected to conventional cytological and fluorescence in situ hybridization (FISH) analyses using the centromeric probes for chromosomes 1, 11, and 17. Histological examination revealed 157 breast cancers and 19 benign diseases (ten fibroadenomas, six intraductal papillomas, one intracystic papilloma, and two ADH). Sensitivity, specificity, and diagnostic accuracy were 85.4% 94.7%, and 86.4%, respectively, for cytology and 90.4%, 100%, and 91.5%, respectively, for FISH. These results demonstrate that FISH diagnosis of FNA samples has a diagnostic accuracy comparable to that of conventional cytology.

For the development of new drugs for hitherto untreatable epilepsy, it is necessary to clarify the basic pathophysiology involved in such epileptic seizures and find the target site. This review focused on molecular events related to the expression and expansion of the epileptic focus which are the target of novel antiepileptics. Immediate early genes such as c-fos followed by expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been evidenced as initial important phenomena in the cascade of molecular systems that develop and complement the transient neuronal excitation to long-term neuronal plasticity. Non-receptor type tyrosine kinase Fyn in the Src family has been suggested to promote kindling development via tyrosine phosphorylation of the NMDA-receptor subunit, NR2B. The cause of abnormality in the inhibitory system is induced by lowering of glutamate-dependent GABA release in the epileptic focus within the hippocampus in human temporal epilepsy. This is probably attributed to a decrease in GABA transporters. Regarding abnormality of the excitatory system, there is an increase in glutamate release prior to convulsive seizures, an enhancement of NMDA receptor responsiveness and high levels of AMPA receptors related to convulsion after completion of kindling. In gene analysis of human familiar epilepsy, abnormalities and point mutations have recently been found in the following genes: KCNQ 2 and KCNQ3, coding for K+ channels; CHRNA4 of the nicotinic receptor subunit alpha 4; and the cystatin B gene. In epilepsy model mice, EL mice with several gene mutations known to be involved in the seizures, the El-1 gene contains an abnormality of the ceruloplasmin gene. SER (spontaneously epileptic rat: zi/zi, tm/tm), a double mutant, manifests a deletion of the region containing the aspartoacylase gene related to the tm gene. Since an increase in N-acetyl-L-aspartate (NAA) is observed in the SER brain, NAA may serve to evoke seizures.

The functions of sigma (sigma) receptors were reviewed based on electrophysiological studies. Systemic administration of sigma ligands reportedly produces a variety of effects on dopamine (DA) neurons. In the mesolimbic DA system, (+)SKF-10,047 suppressed activities of the ventral tegmental area. In the substantia nigra, DTG also suppressed these activities, while BMY-14802 increased the activity of neurons. In the cerebellum, however, activities of Purkinje cells were suppressed by locally applied DTG, with probable involvement of the catecholaminergic system. This effect on Purkinje cells may explain the action of sigma ligands on the motor system. In the hippocampus, neuronal activities were inhibited by SR31742A in vivo (CA3 region) and by (+)SKF10,047 in vitro (CA1 region). DTG at high concentration (1 mM) completely suppressed population spikes (PS) in the CA1 region of hippocampal slice preparations. In our experiments, a novel sigma ligand, OPC-24439, suppressed PS in CA1 at concentrations of 1-100 microM. However, NMDA-induced neuronal firings in CA3 in vivo were augmented by low doses of DTG in a haloperidol-sensitive manner, but high doses were ineffective. In contrast, non-NMDA responses were not affected by DTG. In addition, several sigma ligands having no effect on the NMDA response have been reported. In addition, endogenous ligands, neuropeptide Y and dehydroepiandrosterone, augmented the NMDA-induced firing. In whole-cell patch clamp recording, NMDA-induced currents were suppressed by a relatively higher concentration of DTG in a concentration-dependent manner, while non-NMDA responses were only slightly suppressed. These findings suggest that effects of sigma ligands on NMDA receptor responses are biphasic, and sigma ligands may modulate memory and learning and suppress neuronal death by anoxia. In addition, sigma ligands are also reported to suppress Ca2+ channels in hippocampal culture neurons and induce current by closing K+ channels in NCB-20 cells. Thus, sigma receptors may be involved in the modulation of a variety of neurons that relate to psychiatric function and plasticity.

Rotational and functional motor behavioral changes were studied in five MPTP lesioned chronic hemiparkinsonian Macaca nemestrina monkeys after i.m. pramipexole, a predominant D2 subfamily agonist. Pramipexole induced contraversive rotations in a dose-dependent manner with an optimal dose of 56 microg/kg for approximately 2 to 4 hr after injection. Three different rating scales were used to determine drug-induced functional improvement. They included a monkey parkinsonism rating scale, volitional responses to fruit presentations, and number of hand movements that appeared volitional. A dose of 56 microg/kg of pramipexole produced functional improvements on hand disability, and on a parkinsonian rating scale for monkeys in a dose-dependent manner from 32 to 100 microg/kg. These doses produced an increase in significant hand movements in the affected (contralateral) as well as in the normal (ipsilateral) hand to the side of the brain lesion compared with 5% dextrose in water vehicle control. With a dose of 100 microg/kg, the therapeutic effects of pramipexole on hand movements were less than with 56 microg/kg, due to side effects such as scratching.

Effects of ethanol on acutely dissociated medial vestibular nucleus (MVN) neurons were examined using whole-cell patch clamp technique to elucidate the mechanism underling the inhibitory effects of this drug on the neurons observed in in vivo studies. Dissociated MVN neurons obtained from male Wistar rats were superfused with extracellular solution continuously at a flow rate of 1-3 ml/min. Whole-cell patch clamp recording was performed according to standard procedures. GABA was applied by pressure from a pipette placed near the neuron recorded. Ethanol was applied via pipette by pressure or through bath perfusion. Acutely dissociated MVN neurons regularly showed spontaneous firing. Under current-clamp conditions, bath application of ethanol at 0.1% caused hyperpolarization and reduced spontaneous firing in MVN neurons, while 0.1% ethanol did not affect spontaneous firing. Pulse application of higher concentrations of ethanol (0.1-1%) caused similar hyperpolarization. Under voltage-clamp conditions at a holding potential of -30 mV, GABA induced outward currents in a concentration-dependent manner. GABA-induced currents were potentiated in the presence of 0.01% ethanol. These results indicate that high concentrations of ethanol (0.1-1%) directly induce inhibition of spontaneous firing and low concentrations (0.01%) enhance GABA-induced inhibition in the MVN neurons.

The role of D2/D3 receptors in striatum was electrophysiologically examined in vitro in chloralose-anesthetized rats. In addition, in vitro patch clamp method with rat brain slices was followed. Stimulations of the substantia nigra pars compacta (SN) in vivo elicited spike generation which was inhibited by microiontophoretically applied domperidone, a D2 antagonist. These domperidone-sensitive neurons were activated by microiontophoretic application of D2 agonists such as talipexole, quinpirole and bromocriptine as well as the D2 agonist, 7-OH-DPAT. They were also excited by either intravenous injection of bromocriptine or talipexole in a dose-dependent manner. Furthermore, the SN-induced increases in neuronal firing were blocked during microiontophoretic application of domperidone. In patch clamp whole-cell recording large-sized cells, identified visually under Ramanosky microscope, were depolarized with repetitive firing on bath application of talipexole and 7-OH-DPAT at a current clamp mode. Talipexole-induced depolarization in the large-sized cell was similarly observed in the presence of TTX and high Mg2+ in Ca(2+)-free physiological solution. In contrast, the medium-sized cells were hyperpolarized on bath application of talipexole without being affected by 7-OH-DPAT. These findings suggest that the large-sized cells, which were presumably cholinergic interneurons, are activated by dopamine derived from the SN via D2 and/or D3 receptors, while the medium-sized cells are inhibited by dopamine via D2 receptors.

A mutant showing convulsive seizures spontaneously in a CJ: Wistar colony was named the Noda epileptic rat (NER). The NER exhibits tonic-clonic convulsion without any external stimuli once every 30 h. However, we succeeded in inducing similar convulsive seizures by applying priming sound stimuli (95 dB, 8 kHz, 30 sec) from 3 weeks of age in all 24 NER examined. When the effects of clinically available antiepileptics were tested on the seizures of such primed NER, the most potent agents were carbamazepine, diazepam, valproate, phenobarbital and trimethadione, while phenytoin and zonisamide showed lower potency. Furthermore, ethosuximide was not effective in inhibiting the seizures. In hippocampal slices of NER with convulsive seizures, repetitive firing accompanied by long-lasting depolarization was observed when a single stimulation was delivered to the mossy fibers in the CA3 pyramidal cell. This depolarization shift was completely blocked with a Ca2+ antagonist (nicardipine 10 nM). The long-lasting hyperpolarization that followed the repetitive firing was also observed with mossy fiber stimulation in the hippocampal CA3 pyramidal cells of the NER. These findings suggest that Ca2+ channel abnormality of the hippocampal CA3 pyramidal cells may be involved in the convulsive seizures.

When asakusanori was incubated in artificial seawater, it released a significant amount of vitamin B12. The rate of release was very high at the beginning of incubation and steeply decreased. Four-fifths of the released B12 was a macromolecule-bound form and the rest was free form, of which some were taken up by the asakusanori tissue. Asakusanori took up the free form B12 from the incubation medium by concentration- and temperature-dependent processes. The amount of uptake increased with the time of incubation and did not attain a plateau after 4 h. The capacity was retained even after storage in frozen state for 11 months.

Comparison of acquired mutations in the p53 tumor suppressor gene can illuminate factors contributing to carcinogenesis among cancer cohorts. Japan has an ethnically homogeneous population with a low incidence of breast cancer. Previously we reported an unusual frequency, allelic status, and clustering of mutations in breast cancers from the northern part of the main Japanese island. To extend these findings, exons 2-11 and adjacent intronic sequences were analysed in tumors of women from northern (Hokkaido) and southern (Tokushima) Japan. The frequency of breast cancers with p53 gene mutations in the Hokkaido group is the highest reported (81%) while that in Tokushima (28%) is similar to most other populations. Thirteen of the 19 mutations (68.4%) in the Hokkaido cohort were heterozygous, an unusually high frequency for p53 mutations in any tumor type. There were three missense mutations at codon 175, a known hotspot for alterations in the p53 gene, and three missense mutations at codon 179, a rare site for p53 changes. In addition, the patterns of p53 gene mutation differed between the two Japanese cohorts (P=0.04). The multiple differences in acquired p53 mutations suggest unsuspected biological differences among breast cancers in northern and southern Japan. In addition, the high frequency of p53 mutations in breast cancers from Hokkaido predicted a poorer prognosis for this population which was confirmed on examination of mortality data.

Effects of a neurosteroid, 20-hydroxyecdysone (20-HE), on epileptic seizures of spontaneously epileptic rat (SER: zi/zi, tm/tm), medial vestibular nucleus (MVN) neurons and GABA-induced currents in primarily cultured cortical neurons were examined. 20-HE (10–50mg/kg) inhibited tonic convulsions in SER without affecting the absence-like seizures. The inhibition was antagonized by pretreatment with bicuculline. The rotation-induced firing of the MVN neuron was inhibited by microiontophoretically applied 20-HE. Similarly this inhibition was antagonized by bicuculline. Using whole-cell patch clamp method application of 20-HE with the U-tube system did not affect the membrane potential, but potentiated GABA-induced hyperpolarization and current at all membrane potentials without affecting the reversal potential of approximately—18mV. These results suggest that 20-HE acts on GABAA receptor, probably at a modulatory site to inhibit the seizure and response of MVN neurons.

To examine the effects of Zn2+ on glutamate-induced neurotoxicity in cultured retinal neurons.Primary cultures obtained from fetal rat retinas (16 to 19 days gestation) were used. The neurotoxic effects of excitatory amino acids were quantitatively assessed using the trypan blue exclusion method.A brief exposure of retinal cultures to glutamate or N-methyl-D-aspartate (NMDA) induced delayed cell death. Zn2+ at concentrations of 3 to 30 microM ameliorated glutamate- and NMDA-induced neurotoxicity in a dose-dependent manner. By contrast, neurotoxicity induced by a 1-hour exposure to kainate was not affected by Zn2+.These findings demonstrate that Zn2+ protects retinal neurons from NMDA receptor-mediated glutamate neurotoxicity.

Summary: We examined the effects of conventional antiepileptic drugs (AEDs) on absence-like seizures in homozygous tremor rats (tm/tm) to determine if they corresponded pharmacologically to human absence seizures and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tdtm) with both tonic convulsive and absence-like seizures. Cortical and hippocampal EEG activity was recorded with chronically implanted electrodes. The effects of AEDS on seizures of the tremor rat showed profiles similar to those observed in human absence seizures and also in absence-like seizures of SER. The absence-like seizures, associated with paroxysmal bursts of 5–7–Hz spike-wave complexes, were inhibited by trimethadione (TMO 200 mg/kg intraperitoneally, i.p.), ethosuximide (ESM100 and 200 mg/kg, i.p.), valproate (VPA100 mg/kg, i.p.), and phenobarbital (PB10 and 20 mg/kg, i.p.1. Phenytoin (PHT 20 mg/kg, i.p.) was ineffective. These results are consistent with the conclusion that the tremor rat is a useful model for evaluating new AEDS for human absence seizures.

The effects of nicardipine, a Ca2+ channel antagonist, on the abnormal excitability of hippocampal CA3 neurons in spontaneously epileptic rats (SER), a double mutant (zi/zi, tm/tm), were examined to elucidate whether or not the abnormality was due to that of Ca2+ channels. An intracellular recording study was performed using brain slice preparations of SER 12–15 weeks of age, when SER showed both tonic convulsions and absence-like seizures. Bath application of nicardipine (10 nM) completely inhibited the depolarizing shifts lasting for 60–120 ms and accompanying repetitive firings on mossy fiber stimulation in SER. However, this drug did not affect the single action potential induced by the mossy fiber stimulation in CA3 neurons of SER and normal Wistar rats. In the CA3 pyramidal neurons of SER, the Ca2+ spikes induced by the depolarizing pulse applied in the cell in the presence of tetrodotoxin and tetraethylammonium had a different configuration from that in normal Wistar rats. Nicardipine also inhibited the Ca2+ spikes in SER CA3 neurons at a concentration (1 nM) that had no effect on those in normal Wistar rats, while the Ca2+ spikes in Wistar rat CA3 neurons were inhibited by 10 nM nicardipine. These findings suggest that the abnormal excitability of CA3 pyramidal neurons in SER might be attributed to abnormalities of the Ca2+ channels, and that the Ca2+ channel antagonist may be effective as an antiepileptic drug.

The patient was a 38-year-old woman who was diagnosed as having right breast cancer (T1aN1bM0, stage II) at the age of 36 when she underwent right mastectomy. Postoperative adjuvant therapy was performed using UFT and tamoxifen. After 2 years and 4 months, pulmonary metastasis was diagnosed from elevated tumor markers and chest X-P. After the relapse, treatment with goserelin acetate (Zoladex) and CPA was started. After 2 months of this treatment, the tumor in the lung had shrunk in size, and after 5 months partial remission (PR) was evaluated from improvements in chest X-P and normalization of tumor markers, This PR condition continues at present. A case report is presented of a patient with premenopausal recurrent breast cancer in whom good results were obtained by concomitant administration of Zoladex and CPA.

At age 35, the patient was diagnosed with left breast carcinoma (T4bN0M0, Stage IIIb) during her first pregnancy, and underwent mastectomy of the left breast and bilateral oophorectomy. Although CPA was administered as adjuvant chemotherapy after the operation, left pelvic pain developed about a year after the operation, and bone metastasis was detected from the imaging diagnosis. Then, the therapy was switched to UFT (600 mg/day) and tamoxifen (20 mg/day), which markedly relieved the pain along with bone scintiscan (NC) and simple X-P (NC). Five years have passed since the operation, and the progress is excellent. There is neither increase of pain nor adverse reactions to drugs. Furthermore, the patient received breast reconstruction operation at her strong insistence in the third year after operation, and has achieved a high quality of life (QOL).

A mass screening trial for breast cancer using mammography was carried out in Tokushima Prefecture, either itinerant screening in the communities or center screening at the workplace. Craniocaudal and lateral oblique imagings of the breast using two-view film mammography were performed at the first stage of screening. In addition, physical examination of the breast was also performed on subjects independently. A total of 8 cases with breast cancer were found in these trials by mammography alone, and no cases with breast cancer were detected by physical examination. The detection rates were 0.19% in itinerant screening, and 0.92% in center screening, respectively. This was much higher than the level (0.10%) obtained by mass screening using physical examination alone in Japan. Moreover, in elderly patients (age over 50 years), the detection rates were higher (0.54%, 1.21%). The number of clinical stage for cases with breast cancer detected by these screening were 5 cases in TIS and 3 in stage I. Thus, all cases were patients with early-stage breast cancer. From these results, mass screening using mammography should be mandatory for elderly women (over 50 years) with asymptomatic breasts.

The electrophysiologic study using patch-clamp techniques demonstrated that NMDA-induced currents had properties similar to those recorded in the brain.Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. Immunocytochemical and electrophysiologic studies were done to identify the cultured cells. The neurotoxic effects of glutamate or N-methyl-D-aspartate (NMDA) on the retinal cultures were quantitatively assessed using the trypan blue exclusion method.The immunocytochemical study revealed that the major component of the rat retinal cultures was neurons including amacrine cells. The electrophysiologic study using patch-clamp techniques demonstrated that exposure to NMDA-induced currents with properties characteristic of those recorded in the brain. Brief exposure of these neurons to glutamate or NMDA induced delayed cell death. Glutamate neurotoxicity was prevented by the application of dopamine and forskolin. The protective action of dopamine was antagonized by a D1 receptor antagonist (SCH 23390) but not by D2 receptor antagonists (domperidone and sulpiride). A D1 receptor agonist (SKF 38393) protected glutamate-induced neurotoxicity in a concentration-dependent manner, whereas a D2 receptor agonist (quinpirole) did not affect it.These findings demonstrate that dopamine protects retinal neuronal cells against NMDA receptor-mediated glutamate neurotoxicity via D1 receptors.

Neuroprotective effects of ifenprodil, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, against glutamate cytotoxicity were examined in cultured rat cortical neurons. The viability of the cultures was markedly reduced by a 10-min exposure to glutamate followed by incubation with glutamate-free medium for 60 min. Ifenprodil and its derivative SL 82.0715 dose-dependently prevented cell death induced by glutamate. The NMDA antagonists MK-801 and 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid also prevented glutamate cytotoxicity with a potency similar to that of ifenprodil. Ifenprodil as well as MK-801 prevented NMDA-induced cytotoxicity, but did not affect kainate-induced cytotoxicity. Glutamate cytotoxicity was inhibited by removing extracellular Ca++ during and immediately after glutamate exposure. Ifenprodil and MK-801 reduced NMDA-induced Ca++ influx measured with rhod-2. Either spermidine, a polyamine modulatory site agonist, or glycine, a strychnine-insensitive glycine site agonist, potentiated NMDA- and glutamate-induced cytotoxicity. The protective effects of ifenprodil against NMDA- and glutamate-induced cytotoxicity were significantly reduced by spermidine, but not by glycine. These findings indicate that ifenprodil protects cortical neurons against glutamate cytotoxicity by selective antagonism of the polyamine modulatory site of the NMDA receptor complex.