Normal strength (NSC) and high-performance concretes (HPC) are being used extensively in the construction of structures that might be subjected to elevated temperatures. The behaviour of concrete structures at elevated temperatures is of significant importance in predicting the safety of structures in response to certain accidents or particular service conditions. This paper deals with the mechanical properties of concrete made with ground granulated blast furnace slag (GGBFS) subjected to temperatures up to 350 °C. For this purpose, normal concrete having compressive strength of 34 MPa was designed using GGBFS as partial replacement of cement. Cylindrical specimens (150 × 300 mm) were made and subjected to temperatures of 100, 200 and 350 °C. Measurements were taken for mass loss, compressive strength, splitting tensile strength, and modulus of elasticity. This investigation developed some important data on the properties of concrete exposed to elevated temperatures up to 350 °C.

Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were targeted to symptomatic patients. However, dopamine loss is at least 60% by the time PD is symptomatically detectable, therefore lack of effect of MAO-B inhibition in these patients does not negate a role for MAO-B in pre-symptomatic dopaminergic loss. In order to directly evaluate the role of age-related elevations in astroglial MAO-B in the early initiation or progression of PD, we created genetically engineered transgenic mice in which MAO-B levels could be specifically induced within astroglia in adult animals. Elevated astrocytic MAO-B mimicking age related increase resulted in specific, selective and progressive loss of dopaminergic neurons in the substantia nigra (SN), the same subset of neurons primarily impacted in the human condition. This was accompanied by other PD-related alterations including selective decreases in mitochondrial complex I activity and increased mitochondrial oxidative stress. Along with a global astrogliosis, we observed local microglial activation within the SN. These pathologies correlated with decreased locomotor activity. Importantly, these events occurred even in the absence of the PD-inducing neurotoxin MPTP. Our data demonstrates that elevation of murine astrocytic MAO-B by itself can induce several phenotypes of PD, signifying that MAO-B could be directly involved in multiple aspects of disease neuropathology. Mechanistically this may involve increases in membrane permeant H(2)O(2) which can oxidize dopamine within dopaminergic neurons to dopaminochrome which, via interaction with mitochondrial complex I, can result in increased mitochondrial superoxide. Our inducible astrocytic MAO-B transgenic provides a novel model for exploring pathways involved in initiation and progression of several key features associated with PD pathology and for therapeutic drug testing.

Impairment of the ubiquitin proteasome system (UPS) and iron accumulation in the substantia nigra (SN) have both been implicated in the pathogenesis of Parkinson's disease (PD). We previously reported that chemical iron chelation can protect against proteasome inhibitor lactacystin-induced dopamine (DA) neurodegeneration in vivo. Here, we tested potential neuroprotection via genetic expression of the iron chelator human ferritin heavy chain (H-ferritin). We found that overexpression of H-ferritin in DA neurons significantly reduced lactacystin-induced nigral DA neuron loss and striatal DA depletion. Overexpression of H-ferritin also attenuated elevated levels of total and ferrous iron as well as the divalent metal ion transporter 1 (DMT1) in the SN following lactacystin treatment. In addition, overexpression of H-ferritin alleviated the inhibitory effects of lactacystin on proteasome activity in the nigral tissues. These results suggest that H-ferritin exerts neuroprotection possibly by modulating iron homeostasis and restoring proteasome activity.

Glutathione depletion is one of the earliest detectable events in the Parkinsonian substantia nigra (SN), but whether it is causative for ensuing molecular events associated with the disease is unknown. Here we report that reduction in levels of glutathione in immortalized midbrain-derived dopaminergic neurons results in increases in the cellular labile iron pool (LIP). This increase is independent of either iron regulatory protein/iron regulatory element (IRP/IRE) or hypoxia inducible factor (HIF) induction but is both H202 and protein synthesis-dependent. Our findings suggest a novel mechanistic link between dopaminergic glutathione depletion and increased iron levels based on translational activation of TfR1. This may have important implications for neurodegeneration associated with Parkinson's disease in which both glutathione reduction and iron elevation have been implicated.

While ferritin elevation within dopaminergic (DA) neurons of the substantia nigra (SN) is protective against neurodegeneration elicited by two toxin models of Parkinson's disease (PD), MPTP and paraquat, in young animals, its prolonged elevation results in a selective age-related neurodegeneration.A similar age-related neurodegeneration has been reported in iron regulatory protein 2-deficient (IRP2 -/-) mice coinciding with increased ferritin levels within degenerating neurons.This has been speculated to be due to subsequent reductions in the labile iron pool (LIP) needed for the synthesis of iron-sulfur-containing enzymes.In order to assess whether LIP reduction is responsible for age related-neurodegeneration in our ferritin transgenics, we examined LIP levels in ferritin-expressing transgenics with increasing age.While LIP levels were reduced within DA SN nerve terminals isolated from young ferritin transgenics compared to wildtype littermate controls, they were found to be increased in older transgenic animals at the age at which selective neurodegeneration is first noted.Furthermore, administration of the bioavailable iron chelator, clioquinol (CQ), to older mice was found to protect against both increased LIP and subsequent dopaminergic neurodegeneration.This suggests that age-related neurodegeneration in these mice is likely due to increased iron availability rather than its reduction.This may have important implications for PD and other related neurodegenerative conditions in which iron and ferritin have been implicated.

Parkinson's disease (PD) is characterized by early glutathione depletion in the substantia nigra (SN). Among its various functions in the cell, glutathione acts as a substrate for the mitochondrial enzyme glutaredoxin 2 (Grx2). Grx2 is involved in glutathionylation of protein cysteine sulfhydryl residues in the mitochondria. Although monothiol glutathione-dependent oxidoreductases (Grxs) have previously been demonstrated to be involved in iron-sulfur (Fe-S) center biogenesis, including that in yeast, here we report data suggesting the involvement of mitochondrial Grx2, a dithiol Grx, in iron-sulfur biogenesis in a mammalian dopaminergic cell line. Given that mitochondrial dysfunction and increased cellular iron levels are two important hallmarks of PD, this suggests a novel potential mechanism by which glutathione depletion may affect these processes in dopaminergic neurons. We report that depletion of glutathione as substrate results in a dose-dependent Grx2 inhibition and decreased iron incorporation into a mitochondrial complex I (CI) and aconitase (m-aconitase). Mitochondrial Grx2 inhibition through siRNA results in a corresponding decrease in CI and m-aconitase activities. It also results in significant increases in iron-regulatory protein (IRP) binding, likely as a consequence of conversion of Fe-S-containing cellular aconitase to its non-Fe-S-containing IRP1 form. This is accompanied by increased transferrin receptor, decreased ferritin, and subsequent increases in mitochondrial iron levels. This suggests that glutathione depletion may affect important pathologic cellular events associated with PD through its effects on Grx2 activity and mitochondrial Fe-S biogenesis.

Ferritin elevation has been reported by some laboratories to occur within the substantia nigra (SN), the area of the brain affected in Parkinson's disease (PD), but whether such an increase could be causatively involved in neurodegeneration associated with the disorder is unknown. Here, we report that chronic ferritin elevation in midbrain dopamine-containing neurons results in a progressive age-related neurodegeneration of these cells. This provides strong evidence that chronic ferritin overload could be directly involved in age-related neurodegeneration such as occurs in Parkinson's and other related diseases.

Parkinson's disease is a neurodegenerative disorder characterized by the preferential loss of midbrain dopaminergic neurons in the substantia nigra (SN). One of the earliest detectable biochemical alterations that occurs in the Parkinsonian brain is a marked reduction in SN levels of total glutathione (glutathione plus glutathione disulfide), occurring before losses in mitochondrial complex I (CI) activity, striatal dopamine levels, or midbrain dopaminergic neurodegeneration associated with the disease. Previous in vitro data from our laboratory has suggested that prolonged depletion of dopaminergic glutathione results in selective impairment of mitochondrial complex I activity through a reversible thiol oxidation event. To address the effects of depletion in dopaminergic glutathione levels in vivo on the nigrostriatal system, we created genetically engineered transgenic mouse lines in which expression of γ-glutamyl cysteine ligase, the rate-limiting enzyme in de novo glutathione synthesis, can be inducibly downregulated in catecholaminergic neurons, including those of the SN. A novel method for isolation of purified dopaminergic striatal synaptosomes was used to study the impact of dopaminergic glutathione depletion on mitochondrial events demonstrated previously to occur in vitro as a consequence of this alteration. Dopaminergic glutathione depletion was found to result in a selective reversible thiol-oxidation-dependent mitochondrial complex I inhibition, followed by an age-related nigrostriatal neurodegeneration. This suggests that depletion in glutathione within dopaminergic SN neurons has a direct impact on mitochondrial complex I activity via increased nitric oxide-related thiol oxidation and age-related dopaminergic SN cell loss.

Selective dopaminergic cell loss in Parkinson's disease is correlated with increased levels of cellular iron. It is still hotly debated as to whether the increase in iron is an upstream event which acts to promote neurodegeneration via formation of oxidative stress or whether iron accumulates as a by-product of the neuronal cell loss. Here we review evidence for loss of iron homeostasis as a causative factor in disease-associated neurodegeneration and the primary players which may be involved. A series of recent studies suggest that iron regulatory proteins (IRPs) coordinate both cellular iron levels and energy metabolism, both of which are disrupted in Parkinson's disease (PD) and may in turn contribute to increased levels of oxidative stress associated with the disease. Iron has also been recently been implicated in promotion of α-synuclein aggregation either directly or via increasing levels of oxidative stress suggesting an important role for it in Lewy body formation, another important hallmark of the disease.

Studies on postmortem brains from Parkinson's patients reveal elevated iron in the substantia nigra (SN). Selective cell death in this brain region is associated with oxidative stress, which may be exacerbated by the presence of excess iron. Whether iron plays a causative role in cell death, however, is controversial. Here, we explore the effects of iron chelation via either transgenic expression of the iron binding protein ferritin or oral administration of the bioavailable metal chelator clioquinol (CQ) on susceptibility to the Parkinson's-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrapyridine (MPTP). Reduction in reactive iron by either genetic or pharmacological means was found to be well tolerated in animals in our studies and to result in protection against the toxin, suggesting that iron chelation may be an effective therapy for prevention and treatment of the disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease involving neurodegeneration of dopaminergic neurons of the substantia nigra (SN), a part of the midbrain. Oxidative stress has been implicated to play a major role in the neuronal cell death associated with PD. Importantly, there is a drastic depletion in cytoplasmic levels of the thiol tripeptide glutathione within the SN of PD patients. Glutathione (GSH) exhibits several functions in the brain chiefly acting as an antioxidant and a redox regulator. GSH depletion has been shown to affect mitochondrial function probably via selective inhibition of mitochondrial complex I activity. An important biochemical feature of neurodegeneration during PD is the presence of abnormal protein aggregates present as intracytoplasmic inclusions called Lewy bodies. Oxidative damage via GSH depletion might also accelerate the build-up of defective proteins leading to cell death of SN dopaminergic neurons by impairing the ubiquitin–proteasome pathway of protein degradation. Replenishment of normal glutathione levels within the brain may hold an important key to therapeutics for PD. Several reports have suggested that iron accumulation in the SN patients might also contribute to oxidative stress during PD.

Levels of iron are increased in the brains of Parkinson's disease (PD) patients compared to age-matched controls. This has been postulated to contribute to progression of the disease via several mechanisms including exacerbation of oxidative stress, initiation of inflammatory responses and triggering of Lewy body formation. In this minireview, we examine the putative role of iron in PD and its pharmacological chelation as a prospective therapeutic for the disease.

Several exciting new scientific advances have been made in the past decade toward both understanding the causes of and finding a cure for Parkinson’s disease. Heartened by an acceleration in research findings in the past several years, the government has recently called for an infusion of funds from both the National Institutes of Health and private foundations into this burgeoning area of biomedical research. Most currently available conventional treatments for the disease only temporarily delay symptom presentation while doing nothing to halt disease progression. However, the rapidly accelerating pace of research in this field has left researchers hopeful that Parkinson’s will be the first major age-related neurodegenerative disease for which we have a viable cure. In this article, advances in various areas of Parkinson’s disease research are reviewed.

Eight local, nondescript adult donkeys, sero-negative to EHV-1, were experimentally infected in two different experiments with EHV-1 of horse origin to study the establishment of viral infection in donkeys along with four pony mares as the control. The virus persisted up to 7 days along with clinical manifestations in pony mares in both the experiments. The virus was also detected by PCR from the spleen of one of the pony mares, but both virus isolation and PCR studies carried out on nasal discharges, peripheral blood lymphocytes and tissues of the animals sacrificed at the end of the experiment, negated the presence of EHV-1 in donkeys. The infectivity and viability of EHV-1 used as the inoculum in both donkey and pony mares was confirmed by isolation of EHV-1and detection of its DNA by PCR from the nasal swabs of pony mares. The use of dexamethasone as an immunosuppresant, failed to indicate the establishment of EHV-1 infection in the donkeys as the virus could not be revived, isolated and detected in PCR studies.

The nutrient profile and levels of antinutritional factors of five high yielding varieties of rice bean (Vigna umbellata) and one variety each of green gram and black gram were investigated. The proximate compositions of rice bean varieties did not vary significantly among themselves and were comparable with those of green gram and black gram, except for protein content, which was significantly lower in rice bean. However, the concentrations of riboflavin and ascorbic acid varied significantly among the rice bean varieties and were comparable with those of green gram and black gram. Amounts of unsaturated fatty acids were higher than saturated. There were some significant differences among the rice bean varieties in their total and extractable mineral contents, which were comparable with those of green gram and black gram, except for calcium, which was twice as great in rice bean than in black gram and green gram. The trypsin inhibitor activity and contents of phytic acid, polyphenolic compounds and saponins varied significantly.

The present investigation was conducted to study the in-vitro starch and protein digestibility of five high-yielding varieties (RB-4, RB-32, RB-37, RB-40 and RB-53) of rice bean (Vigna umbellata) and one variety each of green gram (K-851) and black gram (MT-9) as affected by various domestic processing and cooking methods which included soaking in tap water for 6, 12 and 18 h; sprouting for 40 and 60 h; ordinary cooking of unsoaked seeds and seeds soaked for 12 h; and autoclaving of unsoaked and soaked seeds. In-vitro starch digestibility (mg maltose released/g meal) and protein digestibility (per cent) of raw rice bean varied from 29·3 to 36·5, and 57·2 to 62·8, respectively. Both starch and protein digestibilities improved significantly on soaking, sprouting, cooking and autoclaving. There was a progressive and significant increase in starch and protein digestibility with successive increase in soaking and sprouting period.

The present investigation was conducted to study the concentration of polyphenols, phytic acid and saponins of five high-yielding varieties of rice bean (Vigna umbellata) and one variety each of green gram and black gram as affected by various domestic processing and cooking methods which included soaking in tap water for 6, 12 and 18 h; sprouting for 40 and 60 h; ordinary cooking of unsoaked and soaked seeds; and autoclaving of unsoaked and soaked seeds. There was a successive and significant reduction in the contents of antinutritional factors with increase in soaking and sprouting period. A markedly greater reduction in these factors was observed when soaked seeds were cooked and autoclaved than when unsoaked seeds were cooked and autoclaved. Among the various domestic processing and cooking methods, maximum reduction of antinutritional factors was observed when soaked seeds were autoclaved.