Powder Injection Moulding of Tool Materials and Materials Containing One-Dimensional Nanostructural Elements

As modern manufacturing methods have been developing, the application methods of powders have changed, and they do not always have to be moulded prior to sintering. The powder injection moulding (PIM) method is suitable for large-lot and mass production; still, powder consumption is not too high. The metal injection moulding (MIM) is an advanced technology and not as developed as classical pressing and sintering but constantly and dynamically developing. The technology is developing towards micro-MIM, that is, production of very small parts for miniaturised devices. The chapter presents the overview of powder injection moulding as specialist powder metallurgy method and its application for fabrication of tool materials. Specially, the fabrication of high-speed steels and carbide-steels on their matrix by powder injection moulding is descripted. In last part of the chapter, the results of own investigations of the structure with nanostructural elements of high-speed steels and carbide-steels on their matrix fabricated by powder injection moulding are presented

Fabrication Technologies of the Sintered Materials Including Materials for Medical and Dental Application

This chapter of the book presents the basis of classical powder metallurgy technologies and discusses powder fabrication, preparation, preliminary moulding, sintering and finish treatment operations. A general description of the materials and products manufactured with the classical powder metallurgy methods is presented. New variants are characterised along with special and hybrid technologies finding their applications in powder metallurgy. Special attention was drawn to microporous titanium and to TiAl6V4 alloy fabricated using hybrid rapid manufacturing technologies with selective laser sintering/selective laser melting (SLS/SLM) used for innovative implant scaffolds in medicine and regenerative dentistry. Laser deposition, thermal spraying and detonation spraying of powders are also discussed as special methods in which powders of metals and other materials are used as raw materials

Bidirectional plasticity of GABAergic tonic inhibition in hippocampal somatostatin- and parvalbumin-containing interneurons

GABAA receptors present in extrasynaptic areas mediate tonic inhibition in hippocampal neurons regulating the performance of neural networks. In this study, we investigated the effect of NMDA-induced plasticity on tonic inhibition in somatostatin- and parvalbumin-containing interneurons. Using pharmacological methods and transgenic mice (SST-Cre/PV-Cre x Ai14), we induced the plasticity of GABAergic transmission in somatostatin- and parvalbumin-containing interneurons by a brief (3 min) application of NMDA. In the whole-cell patch-clamp configuration, we measured tonic currents enhanced by specific agonists (etomidate or gaboxadol). Furthermore, in both the control and NMDA-treated groups, we examined to what extent these changes depend on the regulation of distinct subtypes of GABAA receptors. Tonic conductance in the somatostatin-containing (SST+) interneurons is enhanced after NMDA application, and the observed effect is associated with an increased content of α5-containing GABAARs. Both fast-spiking and non–fast-spiking parvalbumin-positive (PV+) cells showed a reduction of tonic inhibition after plasticity induction. This effect was accompanied in both PV+ interneuron types by a strongly reduced proportion of δ-subunit-containing GABAARs and a relatively small increase in currents mediated by α5-containing GABAARs. Both somatostatin- and parvalbumin-containing interneurons show cell type-dependent and opposite sign plasticity of tonic inhibition. The underlying mechanisms depend on the cell-specific balance of plastic changes in the contents of α5 and δ subunit-containing GABAARs

Composite Materials Infiltrated by Aluminium Alloys Based on Porous Skeletons from Alumina, Mullite and Titanium Produced by Powder Metallurgy Techniques

The infiltration technology with reinforcement in the form of porous skeletons fabricated with powder metallurgy methods has been presented in relation to the general characteristics of metal alloy matrix composite materials. The results of our own investigations are presented pertaining to four alternative technologies of fabrication of porous, sintered skeletons, and their structure and their key technological properties are presented. Porous skeletons made of Al2O3 aluminium are sintered reactively using blowing agents or are manufactured by ceramic injection moulding (CIM) from powder. Porous skeletons made of 3Al2O3⋅2SiO2 mullite are achieved by sintering a mixture of halloysite nanotubes together with agents forming an open structure of pores. Titanium porous skeletons are achieved by selective laser sintering (SLS). The structure and properties of composite materials with an aluminium alloy matrix—mainly EN AC-AlSi12 and also EN AC-AlSi7Mg0.3 alloys—reinforced with the so manufactured skeletons are also described. A unique structure of the achieved composite materials, together with good mechanical properties and abrasive wear resistance at low density, ensured by an aluminium alloy matrix, are indicating broad application possibilities of such composites

The newest methods of treatment of Alzheimer's disease

Choroba Alzheimera (AD) jest postępującą, neurodegeneracyjną chorobą powodującą deteriorację funkcji poznawczych. Jest najbardziej rozpowszechnioną formą demencji. W obrazie neuropatologicznym choroby Alzheimera obserwuje się obecność dwóch głównych czynników patologicznych – blaszek starczych złożonych z β-amyloidu oraz splotów neurofibrylarnych, rdzeniem których jest białko tau. Obecnie brak jest skutecznej terapii przeciwko AD – stosowane leki wykazują tylko krótkotrwałe działanie objawowe, nie wpływając na przyczyny choroby. Rozwój badań podstawowych umożliwił stworzenie wielu teoretycznych podejść do przyczynowej terapii AD. Na ich bazie opracowywane są związki, których bezpieczeństwo użycia i skuteczność sprawdzana jest w badaniach klinicznych.Alzheimer's disease (AD) is a progressive neurodegenerative disease which cause deterioration in cognition. AD is the most prevalent form of dementia. The two main neuropathological hallmarks of Alzheimer's disease are senile plaques consist of β-amyloid and neurofibrillary tangles composed of the tau protein. Right now there is no efficient therapy against Alzheimer's disease – drugs being currently in medical use demonstrate only short-term symptomatic effects and do not interfere with pathological causes responsible for clinical symptoms. Progress in basic research have enabled to develop many theoretical disease-modifying treatment approaches. According to these approaches new drugs against Alzheimer's disease are designed and their efficiancy and safety are verified in clinical trials

"Research on animal model of Parkinson's disease induced by intracerebral injection with proteasome inhibitor - lactacystin"

Choroba Parkinsona jest nieuleczalną, postępującą chorobą neurodegeneracyjną. Jedyne dostępne leki wykazują wyłącznie właściwości symptomatyczne, łagodząc objawy choroby. W celu opracowania nowych leków o potencjale terapeutycznym wykorzystuje się zwierzęce modele choroby Parkinsona. Obecnie prowadzi się badania nad modelami, które najwierniej odzwierciedlają patogenezę choroby. Jednym z nich wydaje się model oparty o zahamowanie proteasomu.Celem prezentowanej pracy było sprawdzenie, czy po jednostronnym podaniu laktacystyny (10 μg/4μl), nieodwracalnego inhibitora proteasomu, do pęczka przyśrodkowego przodomózgowia (MFB) szczura dochodzi do wystąpienia charakterystycznych cech parkinsonizmu (deficytów behawioralnych i zmian biochemicznych). Zbadano katalepsję oraz zachowania rotacyjne wywołane amfetaminą (5 mg/kg) i apomorfiną (0,25 mg/kg). Po dekapitacji szczurów oszacowano poziom dopaminy i innych neuroprzekaźników w prążkowiu i istocie czarnej oraz sprawdzono poziom ekspresji mRNA dla proenkefaliny w prążkowiu.Wykazano katalepsję u szczurów w 1. i 3. dniu po podaniu laktacystyny, która zanikała po 7. dniu od podania toksyny. Zaobserwowano nasilone rotacje ipsilateralne wywołane podaniem amfetaminy oraz brak rotacji kontralateralnych wywołanych podaniem apomorfiny, co sugeruje odmienny w porównaniu do innych modeli mechanizm neurodegeneracyjny laktacystyny. Po raz pierwszy w badanym modelu stwierdzono wzrost ekspresji mRNA dla proenkefaliny w prążkowiu, sugerujący wzrost aktywności „szlaku pośredniego” wychodzącego z prążkowia. Pokazano, że laktacystyna powoduje wysoki spadek poziomu dopaminy w prążkowiu (88%) oraz umiarkowany w istocie czarnej (69%). Otrzymane wyniki podają jednak wysoki poziom zasadności modelu laktacystynowego wywołanego jednostronnym podaniem do MFB w wątpliwość.Parkinson's disease is incurable, progressive and degenerative disorder of central nervous system. Unfortunately, drugs being used to treat Parkinson's disease demonstrate only symptomatic effects, and temporarily alleviate motor symptoms. Animal models of Parkinson's disease are being used to investigate new anti-parkinsonian drugs. Nowadays, scientists make an attempt to build animal models that mimic pathogenesis of Parkinson's disease accurately. The animal model based on inhibition of the proteasome seems to be promising.The aim of the study was to determine if unilateral injection with irreversible proteasome inhibitor, lactacystin (10 μg/4μl), into the rat medial forebrain bundle (MFB) can induce parkinsonian-like symptoms (motor deficits as well as biochemical changes). Rats were tested for catalepsy and rotational behavior induced by amphetamine (5 mg/kg) and apomorphine (0.25 mg/kg). After obtaining behavioral data, rats were killed by decapitation and the levels of dopamine and other neurotransmitters in the substantia nigra and striatum were assayed. Striatal proenkephalin mRNA expression was also determined.Lactacystin evoked catalepsy on the first and third day after injection that decreased starting on seventh day after surgery. High number of ipsilatetral rotations induced by amphetamine and no contralateral rotations induced by apomorphine were demonstrated, what can indicate the difference in mechanism between lactacystin and other toxins used for modelling Parkinson's disease. For the first time increased striatal proenkephalin mRNA expression was found in lactacystin-lesioned rats, indicating hyperactivation of striatal "indirect" pathway. Lactacystin induced high dopamine decrease in striatum (88%) and modest decrease in substantia nigra (69%). All data indicates moderate validity of animal model of Parkinson's disease induced by unilateral injections with lactacystin into medial forebrain bundle

Alpha1-adrenergic receptor blockade in the VTA modulates fear memories and stress responses

Activity of the ventral tegmental area (VTA) and its terminals has been implicated in the Pavlovian associative learning of both stressful and rewarding stimuli. However, the role of the VTA noradrenergic signaling in fear responses remains unclear. We aimed to examine how alpha1-adrenergic receptor (α1-AR) signaling in the VTA affects conditioned fear. The role of α1-AR was assessed using the micro-infusions into the VTA of the selective antagonists (0.1-1 µg/0.5 µl prazosin and 1 µg/0.5 µl terazosin) in acquisition and expression of fear memory. In addition, we performed control experiments with α1-AR blockade in the mammillary bodies (MB) - a brain region with α1-AR expression adjacent to the VTA. Intra-VTA but not intra-MB α1-AR blockade prevented formation and retrieval of fear memories. Importantly, local administration of α1-AR antagonists did not influence footshock sensitivity, locomotion or anxiety-like behaviors. Similarly, α1-AR blockade in the VTA had no effects on negative affect measured as number of 22 kHz ultrasonic vocalizations during fear conditioning training. We propose that noradrenergic signaling in the VTA via α1-AR regulates formation and retrieval of fear memories but not other behavioral responses to stressful environmental stimuli. It enhances the encoding of environmental stimuli by the VTA to form and retrieve conditioned fear memories and to predict future behavioral outcomes. Our results provide novel insight into the role of the VTA α1-AR signaling in the regulation of stress responsiveness and fear memory

Noradrenergic signaling in the VTA modulates cocaine craving

Exposure to drug-associated cues evokes drug-seeking behavior and is regarded as a major cause of relapse. Conditional stimulus upregulates noradrenaline (NA) system activity, but the drug-seeking behavior depends particularly on phasic dopamine signaling downstream from the ventral tegmental area (VTA). The VTA dopamine-ergic activity is regulated via the signaling of alpha1-adrenergic and alpha2-adrenergic receptors (α1-ARs and α2-ARs); thus, the impact of the conditional stimulus on drug-seeking behavior might involve NAergic signaling in the VTA. To date, the role of VTA ARs in regulating cocaine seeking was not studied. We found that cocaine seeking under extinction conditions in male Sprague-Dawley rats was attenuated by intra-VTA prazosin or terazosin-two selective α1-AR antagonists. In contrast, cocaine seeking was facilitated by intra-VTA administration of the selective α -AR agonist phenylephrine as well as α2-AR antagonist RX 821002, whereas the selective β-AR antagonist propranolol had no effects. In addition, blockade of α1-AR in the VTA prevented α2-AR antagonist-induced enhancement of cocaine seeking. Importantly, the potential non-specific effects of the VTA AR blockade on cocaine seeking could be excluded, because none of the AR antagonists influenced sucrose seeking under extinction conditions or locomotor activity in the open field test. These results demonstrate that NAergic signaling potently and selectively regulates cocaine seeking during early cocaine withdrawal via VTA α1-AR and α2-AR but not β-AR. Our findings provide new insight into the NAergic mechanisms that underlie cocaine craving

Bionic Organs: Shear Forces Reduce Pancreatic Islet and Mammalian Cell Viability during the Process of 3D Bioprinting

Background: 3D bioprinting is the future of constructing functional organs. Creating a bioactive scaffold with pancreatic islets presents many challenges. The aim of this paper is to assess how the 3D bioprinting process affects islet viability. Methods: The BioX 3D printer (Cellink), 600 μm inner diameter nozzles, and 3% (w/v) alginate cell carrier solution were used with rat, porcine, and human pancreatic islets. Islets were divided into a control group (culture medium) and 6 experimental groups (each subjected to specific pressure between 15 and 100 kPa). FDA/PI staining was performed to assess the viability of islets. Analogous studies were carried out on α-cells, β-cells, fibroblasts, and endothelial cells. Results: Viability of human pancreatic islets was as follows: 92% for alginate-based control and 94%, 90%, 74%, 48%, 61%, and 59% for 15, 25, 30, 50, 75, and 100 kPa, respectively. Statistically significant differences were observed between control and 50, 75, and 100 kPa, respectively. Similar observations were made for porcine and rat islets. Conclusions: Optimal pressure during 3D bioprinting with pancreatic islets by the extrusion method should be lower than 30 kPa while using 3% (w/v) alginate as a carrier