Aluminum as a Possible Cause Toward Dyslipidemia.

Aluminum, the third most abundant metal present in the earth's crust, is present almost in all daily commodities we use, and exposure to it is unavoidable. The interference of aluminum with various biochemical reactions in the body leads to detrimental health effects, out of which aluminum-induced neurodegeneration is widely studied. However, the effect of aluminum in causing dyslipidemia cannot be neglected. Dyslipidemia is a global health problem, which commences to the cosmic of non-communicable diseases. The interference of aluminum with various iron-dependent enzymatic activities in the tri-carboxylic acid cycle and electron transport chain results in decreased production of mitochondrial adenosine tri-phosphate. This ultimately contributes to oxidative stress and iron-mediated lipid peroxidation. This mitochondrial dysfunction along with modulation of α-ketoglutarate and L-carnitine perturbs lipid metabolism, leading to the atypical accumulation of lipids and dyslipidemia. Respiratory chain disruption because of the accumulation of reduced nicotinamide adenine di-nucleotide as a consequence of oxidative stress and the stimulatory effect of aluminum exposure on glycolysis causes many health issues including fat accumulation, obesity, and other hepatic disorders. One major factor contributing to dyslipidemia and enhanced pro-inflammatory responses is estrogen. Aluminum, being a metalloestrogen, modulates estrogen receptors, and in this world of industrialization and urbanization, we could corner down to metals, particularly aluminum, in the development of dyslipidemia. As per PRISMA guidelines, we did a literature search in four medical databases to give a holistic view of the possible link between aluminum exposure and various biochemical events leading to dyslipidemia.

Short Peptoid Evolved from the Key Hydrophobic Stretch of Amyloid-ß42 Peptide Serves as a Potent Therapeutic Lead of Alzheimer's Disease.

Amyloid-ß 42(Aß42), an enzymatically cleaved (1-42 amino acid long) toxic peptide remnant, has long been reported to play the key role in Alzheimer's disease (AD). Aß42 also plays the key role in the onset of other AD-related factors including hyperphosphorylation of tau protein that forms intracellular neurofibrillary tangles, imbalances in the function of the neurotransmitter acetylcholine, and even generation of reactive oxygen species (ROS), disrupting the cytoskeleton and homeostasis of the cell. To address these issues, researchers have tried to construct several strategies to target multiple aspects of the disease but failed to produce any clinically successful therapeutic molecules. In this article, we report a new peptoid called RA-1 that was designed and constructed from the hydrophobic stretch of the Aß42 peptide, 16KLVFFA21. This hydrophobic stretch is primarily responsible for the Aß42 peptide aggregation. Experimental study showed that the RA-1 peptoid is stable under proteolytic conditions, can stabilize the microtubule, and can inhibit the formation of toxic Aß42 aggregates by attenuating hydrophobic interactions between Aß42 monomers. Furthermore, results from various intracellular assays showed that RA-1 inhibits Aß42 fibril formation caused by the imbalance in AchE activity, reduces the production of cytotoxic reactive oxygen species (ROS), and promotes neurite outgrowth even in the toxic environment. Remarkably, we have also demonstrated that our peptoid has significant ability to improve the cognitive ability and memory impairment in in vivo rats exposed to AlCl3 and d-galactose (d-gal) dementia model. These findings are also validated with histological studies. Overall, our newly developed peptoid emerges as a multimodal potent therapeutic lead molecule against AD.

A Dysfunctional Descending Pain Modulation System in Chronic Nonspecific Low Back Pain: A Systematic Review and ALE Meta-Analysis.

Pain, a physiological protective mechanism, turns into a complex dynamic neural response when it becomes chronic. The role of neuroplastic brain changes is more evident than the peripheral factors in the maintenance, modulation and amplification of chronic low back pain (cLBP). In this background, we summarise the brain changes in cLBP in a coordinate-based activation likelihood estimation (ALE) meta-analysis of previous functional magnetic resonance imaging (fMRI) studies. Databases ('PubMed', 'Scopus' and 'Sleuth') were searched till May 2022 and the activity pattern was noted under the 'without stimulation' and 'with stimulation' groups. A total of 312 studies were selected after removing duplicates. Seventeen (553 cLBP patients, 192 activation foci) studies were fulfilled the eligibility criteria and included in the 'without stimulation' group. Twelve statistically significant clusters are localized in the prefrontal cortex, primary somatosensory cortex, primary motor cortex, parietal cortex, anterior cingulate cortex, caudate, putamen, globus pallidus amygdala, occipital lobe, temporal lobe and associated white matter in this group. Ten studies (353 cLBP patients, 125 activation foci) were selected in the' with stimulation' groups. In this group, seven statistically significant clusters were found in the frontal cortex, orbitofrontal cortex, premotor cortex, parietal cortex, claustrum and insula. These statistically significant clusters indicate a probable imbalance in GABAergic modulation of brain circuits and dysfunction in the descending pain modulation system. This disparity in the pain neuro-matrix is the source of spontaneous and persisting pain in cLBP.

Poor sleep and the metabolic derangements associated with obesity in adult males.

Context: Short sleep and obesity have a causal association with each other. Obesity is also associated with metabolic imbalances. However, a subset of 20%-30% of obese population have only few metabolic complications, known as metabolically healthy obese (MHO) and rest with worsened metabolic profile are known as metabolically abnormal obese (MAO). Aims: To find the association between sleep quality and metabolic health of adult obese males. Settings and Design: The study was a cross-sectional study conducted at medicine out-patient department of the institute. Methods and Material: In this study, hundred adult obese males of age group 25-60 years, with Body mass index (BMI) ≥ 25 Kg/m2, were divided into MHO and MAO, based on their metabolic health using Joint Interim criteria. Sleep quality was assessed using Pittsburgh sleep questionnaire index (PSQI). Statistical analysis used: The data obtained were analyzed using PAST statistical software. Results: The two groups MHO and MAO presented with significant differences in their mean age and BMI (P = 0.0001). The global score of PSQI was significantly high for MAO than MHO with mean values of 8.24 ± 3.60 and 6.65 ± 3.58, respectively (P = 0.016). Sleep disturbances score was significantly high in MAO (P = 0.0001). Significant associations were observed for global score with age, BMI, waist circumference, fasting blood sugar, and triglycerides. Conclusions: Poor sleep quality was significantly associated with detrimental metabolic profile and BMI. The metabolic health worsened with increasing age and obesity.

Critical Self-Appraisal Towards the Better Use of a Webinar Series as an Online Tool for Postgraduate Teaching.

INTRODUCTION: The current coronavirus disease 2019 (COVID-19) pandemic adversely affected the conventional teaching mode, resulting in an exponential rise in online modalities such as webinars. Simultaneously, the lockdown provided substantial time to pursue potential academic content on the web. It is known that newly admitted postgraduate students of Physiology require a structured program that can guide them to conduct research for the completion of the course. METHODS: Gauging the opportunity, a webinar series was conducted on basic research methodology and thesis writing in Physiology. The series comprised hourly lectures delivered between 4:00 and 5:00 pm for seven consecutive days. Suggestions for future topics for webinars were sought through open-ended questions. Additionally, feedback for increment in students' knowledge at the end of the webinar was also inquired on a Likert scale. Open-ended answers were pooled into fields, and Likert scale scores were evaluated. RESULTS: There were 364 (35.8%) postgraduate students who registered for the webinar. The remaining were faculty (51.6%), research scholars (8.8%), and senior residents (3.8%). Among the postgraduate students who submitted the feedback, a majority (98.4%) of them agreed that their knowledge was enhanced at the end of the series. Most of the postgraduate students (31%) chose Biostatistics for future webinars. CONCLUSION: Webinars are a useful tool for postgraduate teaching. They should be constructed with engaging infrastructure and relevant examples. The availability of recorded content on the online forum is beneficial for asynchronous learners. Having an idea about students' choice for essential topics helps in the advanced planning of a demanding webinar.

Dissimilar Anxiety-like Behavior in Prepubertal and Young Adult Female Rats on Acute Exposure to Aluminium.

BACKGROUND: Puberty is a developmental transition in which an estrogenic surge occurs, mediating the release of xenoestrogens, like aluminium. Aluminium's effect on anxiety in rodents at the different developmental stages is inconsistent. AIMS: This study aimed at investigating the effect of the metalloestrogenic property of aluminium on anxiety-like behavioral changes in prepubertal and young adult female rats. OBJECTIVE: Considering this aim, our objective was to evaluate the anxiety-like behavior by the elevated plus maze in prepubertal and young adult female rats with or without acute exposure to aluminium. METHODS: To address this property of aluminium, 5mg/Kg body weight (Al-5) and 10 mg/Kg body weight (Al-10) of aluminium was administered intraperitoneally to female rats at two developmental stages, prepubertal (PP; n = 8 for each dose) and young adult (YA; n = 6 for each dose) for two weeks. Post-treatment, three days behavioral assessment of the rats was done employing elevated plus maze. RESULTS: Reduced escape latency was seen in Al-5, Al-10 pre-pubertal rats, and Al-5 young-adult rats on day 3. A significant reduction in open arm time was seen in the Al-5 young-adult rats. Aluminium treatment in the pre-pubertal rats reduced their head dipping and grooming. Reduced sniffing, head dipping, and stretch-attended posture in the treated young-adult female rats showed that they had impaired risk-taking tendency. CONCLUSION: Differential effect on the anxiety-like behavior in the pre-pubertal and young-adult female rats might be due to the metalloestrogenic property of aluminium, acting differently on the two age groups.

Downregulation of Candidate Gene Expression and Neuroprotection by Piperine in Streptozotocin-Induced Hyperglycemia and Memory Impairment in Rats.

There is accumulating evidence showing that hyperglycemia conditions like diabetes possess a greater risk of impairment to the neuronal system because high glucose levels exacerbate oxidative stress, accumulation of amyloid-beta peptides, and mitochondrial dysfunction, and impair cognitive functions and cause neurodegeneration conditions like Alzheimer's diseases. Due to the extensive focus on pharmacological intervention to prevent neuronal cells' impairment induced by hyperglycemia, the underlying molecular mechanism that links between Diabetes and Alzheimer's is still lacking. Given this, the present study aimed to evaluate the protective effect of piperine on streptozotocin (STZ) induced hyperglycemia and candidate gene expression. In the present study, rats were divided into four groups: control (Vehicle only), diabetic control (STZ only), piperine treated (20 mg/kg day, i.p), and sitagliptin (Positive control) treated. The memory function was assessed by Morris water maze and probe test. After treatment, biochemical parameters such as HOMA index and lipid profile were estimated in the serum, whereas histopathology was evaluated in pancreatic and brain tissue samples. Gene expression studies were done by real-time PCR technique. Present data indicated that piperine caused significant memory improvement as compared to diabetic (STZ) control. The assessment of HOMA indices in serum samples showed that piperine and sitagliptin (positive control, PC) caused significant alterations of insulin resistance, ß cell function, and insulin sensitivity. Assessment of brain and pancreas histopathology shows significant improvement in tissue architecture in piperine and sitagliptin treated groups compared to diabetic control. The gene expression profile in brain tissue shows significantly reduced BACE1, PSEN1, APAF1, CASPASE3, and CATALASE genes in the piperine and sitagliptin (PC) treated groups compared to Diabetic (STZ) control. The present study demonstrated that piperine not only improves memory in diabetic rats but also reduces the expression of specific AD-related genes that can help design a novel strategy for therapeutic intervention at the molecular level.

Live Imaging and Analysis of Vasoactive Properties of Drugs Using an in-ovo Chicken Embryo Model: Replacing and Reducing Animal Testing.

Vasodilation occurs as a result of the relaxation of the smooth muscle cells present in the walls of blood vessels. Various suitable models are available for the analysis of the vasoactive properties of drugs with therapeutic applications. But all these models have limitations, such as ethical issues and high cost. The purpose of this study is to develop an alternative model for studying the vasoactive properties of drugs using an in-ovo chicken embryo model. In the preliminary experiment, we used a well-known vasoconstrictor (adrenaline) and a vasodilator (spermine NoNoate) in the chick embryo area vasculosa and evaluated their concentration-response curve. Adrenaline (10 µM) and spermine NoNoate (10 µM) were administered in different arteries and veins and different positions of the right vitelline artery of the chick embryo. Results showed the middle of the vessel bed of the right vitelline artery having the best vasoactive effect compared to others. Finally, anti-hypertensive drugs, calcium channel blockers, and NOS agonists were administered in the chick embryo area vasculosa to validate the model. Results demonstrate that the chick embryo area vasculosa can be an alternative, robust, and unique in-ovo model for screening of anti-hypertensive drugs in real time.

Alpha-Tocopherol Supplementation Restricts Aluminium- and Ethanol-Induced Oxidative Damage in Rat Brain but Fails to Protect Against Neurobehavioral Damage.

The concurrent presence of oxidative stress (OS) and aluminium exposure is an inducer of neurodegenerative changes. Aluminium can augment OS in a pro-oxidant dominant condition. Antioxidative property of α-tocopherol may be useful in restricting these degenerative changes in the brain. OS parameters are tested in frontal cortex (FC), hippocampus (HC), and cerebellum (CL) of α-tocopherol-supplemented (5 IU/day) male Wistar rats exposed to aluminium (10 mg Al/Kg/day; "Al"), ethanol (0.6 g ethanol/Kg/day; "Et"), and both ("Al-Et") and vehicle-treated control ("C") for 4 weeks. The α-tocopherol supplementation restricted regional alterations of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. Accordingly, the regional superoxide and peroxide handling capacities (SPHC) also remain unaltered. Al-Et group demonstrated significant elevation in the lipid peroxidation level in FC and CL regions compared to the group C; similar elevations in lipid peroxidation were noted in all the tested brain regions of Al group. Likewise, declines in glutathione reductase activity were noted in HC (versus Et group) and CL (versus Al and Et groups) of Al-Et group. Interestingly, changes in behavioral patterns of all the treatment groups are comparable while differing from that of the control group. Significant difference with group C is observed during first through fourth weeks, third to fourth weeks, and second to third weeks in terms of spontaneous motor activity, Rota Rod performance, and Hebb-Williams maze performance, respectively. Hence, the current dose and duration of α-tocopherol supplementation failed to provide full protection against the aluminium-induced neurodegeneration; nevertheless, it could provide only partial protection toward aluminium-induced augmentation of OS in specific brain regions.

Effect of Tocotrienol on medium dose ethanol-induced alternations in serum superoxide and peroxide handling capacities (SPHC) in rat.

Tocotrienols are members of vitamin E family present in low concentrations and possess high antioxidant activity. Consumption of ethanol is a common problem and induces oxidative stress. In this study, we evaluated the effect of tocotrienol against ethanol-induced oxidative stress. Male albino Wistar rats were divided into two sets; one set of rats were exposed with low to moderate doses of ethanol for 4 weeks, while another set was exposed to tocotrienol orally (10 mg/day) in addition to the 'low to moderate doses of ethanol for 4 weeks'. Oxidative stress parameters, like levels of reduced glutathione and lipid peroxidation, activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were determined in serum before the initiation of treatment protocol and at the end of 2nd and 4th week of treatment. Serum levels of superoxide and peroxide handling capacities were also calculated in those three time points. Tocotrienol-treated rats showed statistically significant enhancement in reduced glutathione level, glutathione peroxidase and glutathione reductase activities. Glutathione-dependent superoxide and peroxide handling capacity of those rats were found to be higher. The current study suggests that the tocotrienol-induced protection against the oxidative stress is most likely mediated by glutathione-based system.

Thalamic superoxide and peroxide handling capacity (SPHC): An experimental study with aluminum, ethanol and tocopherol in rats.

Superoxide and peroxide handling capacity (SPHC) is an important determinant of oxidative stress. Neurotoxic impacts of aluminum are associated with oxidant imbalance. Here, we studied the influence of aluminum on oxidative stress parameters, antioxidative enzymes and SPHC of thalamic area on pro-oxidant (ethanol) and antioxidant (α-tocopherol) exposure. Two sets of male Wistar rats were divided into 8 groups (6 each) and exposed to aluminum (10 mg/Kg body wt.), ethanol (0.6 g/Kg body wt.) and α-tocopherol (5 IU/day) for 4 wk, each having respective control group. Levels of reduced glutathione (GSH), lipid peroxidation (TBARS) along with activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) of thalamic area were estimated for each group. Glutathione-independent superoxide peroxide handling capacity (GI-SPHC) and glutathione-dependent superoxide peroxide handling capacity (GD-SPHC) were calculated from the GPx, CAT and SOD values. Concomitant exposure to aluminum and ethanol demonstrated significant increase in SOD activity and significant decrease in GPx activity compared to the control group, while lone aluminum-exposed rats showed raised GR activity, without alterations in GPx and SOD activities. However, significant reduction of both GI- and GD- SPHC were found in ethanol-exposed groups. α-Tocopherol supplementation could resist most of the alterations. In addition, current antioxidant exposure reduced the inherent GD-SPHC, and thus, made thalamic area more vulnerable to oxidant threat. The present study corroborates the thalamic susceptibility to aluminum-augmented oxidant imbalance and suggests cautious use of antioxidant supplementation against neurodegenerative disorders.

Aluminum and ethanol induce alterations in superoxide and peroxide handling capacity (SPHC) in frontal and temporal cortex.

Aluminum is an omnipresent neurotoxicant and has been associated with several neuropathological disorders. Cerebrum and cerebellum have been shown to face augmented oxidative stress when animals are exposed to aluminum and high doses of ethanol. To establish the link between oxidative stress and neurobehavioral alterations, the present study was conducted to determine the extent of oxidative stress in low levels of pro-oxidant (ethanol exposure) status of the functionally discrete regions of the cerebrum. Male Wistar rats were exposed to aluminum (10 mg/kg body wt) and ethanol (0.2-0.6 g/kg body wt) for 4 weeks. Spontaneous motor activity (SMA) and Rota-Rod performances (RRP) were recorded weekly during the period of exposure. At the end of 4th week, oxidative stress parameters were determined from the homogenized cerebral tissue. GSH-independent superoxide peroxide handling capacity (GI-SPHC) and GSH-dependent superoxide peroxide handling capacity (GD-SPHC) were determined for FC and TC upon exposure to ethanol in the absence and presence of aluminum exposure. Aluminum was found to augment the oxidative stress at higher doses (0.6 g Ethanol/kg body wt) of ethanol, particularly in FC. The SPHC of FC was also found to be compromised significantly in aluminum-ethanol co-exposed animals. It was concluded that even though the manifestation of oxidative stress was not observed as revealed by assaying the widely used oxidative stress biochemical markers (indices), aluminum and ethanol (low doses) exposure induced alterations in the handling capacity of oxidant imbalance that could be recognized by studying the SPHC of FC. Comparison of GD-SPHC and GI-SPHC offered a possible mechanism of compromised SPHC in FC. This observation is likely to offer insights into the mechanism of association between aluminium exposure and behavioral changes in neurodegenerative disorders towards therapeutic strategies for these disorders.

Effect of aluminum exposure on superoxide and peroxide handling capacities by liver, kidney, testis and temporal cortex in rat.

Oxidant imbalance is one of the causative mechanisms of aluminum-induced neurotoxicity. In this study, we investigated aluminum-induced oxidant imbalance in non-neuronal tissues (liver, kidney and testis) and temporal cortex in rats. The differences in adaptations to superoxide and peroxide handling capacities (SPHC) of studied organs due to aluminum insult were also evaluated. Male Wistar rats were exposed to aluminum (10 mg/Kg body wt/day) for 4 weeks through orogastric intubation. Liver showed significant decrease in reduced glutathione level, while significant alteration in lipid peroxidation was observed in temporal cortex in aluminium-exposed animals. Superoxide dismutase activity was significantly altered in liver and temporal cortex and catalase activity significantly reduced in the liver due to aluminum exposure, while glutathione reductase and glutathione peroxidase activities were altered in all the tested organs. Among the organs, glutathione-independent SPHC was relatively higher in liver and kidney, while glutathione-dependent SPHC was relatively higher in testis and temporal cortex. As compared to control, aluminum-exposed rats demonstrated reduction in glutathione-dependent SPHC in temporal cortex and increment of the same in testis, while increment in glutathione-independent SPHC was observed in liver. In conclusion, aluminum-induced alteration in oxidant handling capacity could be the cause of oxidative stress both in the neuronal and non-neuronal tissues.

Augmentation of aluminum-induced oxidative stress in rat cerebrum by presence of pro-oxidant (graded doses of ethanol) exposure.

Both aluminum and ethanol are pro-oxidants and neurotoxic. Considering the possibilities of co-exposure and sharing mechanisms of producing neurotoxicity, the present study was planned to identify the level of aluminum-induced oxidative stress in altered pro-oxidant (ethanol exposure) status of cerebrum. Male rats were coexposed to aluminum and ethanol for 4 weeks. After the exposure period, cerebral levels of protein, reduced glutathione (GSH), lipid peroxidation (TBARS) were measured. Activities of catalase, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione perioxidase (GPx) of cerebrum were estimated. In most of the cases significant correlations were observed between the alterations and graded ethanol doses, suggesting a dose-dependency in pushing the oxidant equilibrium toward pro-oxidants. Aluminum is found to influence significantly all the studied parameters of oxidative stress. Likewise, ethanol also influenced these parameters significantly, except GR, while the interaction between ethanol and aluminum could significantly influence only the GSH content and GR activity of cerebrum. Present study demonstrate that coexposure of aluminum with pro-oxidant might favor development of aluminum-induced oxidative stress in cerebrum. This observation might be helpful in understanding of mechanism of neurodegenerative disorders and ameliorate them.

Alpha-tocopherol supplementation on chromium toxicity: a study on rat liver and kidney cell membrane.

Membrane damage is one of the important consequence of chromium, an environmental toxicant, to produce cytotoxicity, alpha-tocopherol, a membrane protectant can be used to reduce the chromium-induced membrane damage. In the present study, the impact of chromium in presence and absence of alpha-tocopherol was studied on plasma membrane of liver and kidney in male Wistar rats (80-100 g body weight). Significant increase in membrane cholesterol level as well as significant decrease in membrane phospholipid level in chromium exposed (0.8 mg/100 g body weight/d, i.p., for 4 weeks) animals suggest structural alteration of both liver and kidney plasma membrane. The alkaline phosphatase, total ATPase and Na(+)-K(+)-ATPase activities of plasma membrane were significantly decreased in both liver and kidney after chromium treatment. However, alpha-tocopherol (30 mg/100 g diet) supplementation can restrict the changes in these membrane-bound enzyme activities. Thus, the usefulness of dietary supplementation of alpha-tocopherol to restrain the chromium-induced membrane damage is suggested.

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain.

BACKGROUND: Alteration of glutamate and gamma-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and gamma-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and gamma-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. RESULTS: Protein restriction does not have any significant impact on regional aluminum and gamma-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate alpha-decarboxylase and gamma-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. CONCLUSION: The alterations of regional brain glutamate and gamma-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders.

Biochemical markers for alcohol consumption.

A variety of laboratory tests are available to assist in the diagnosis of alcohol consumption and related disorders. The levels of intake at which laboratory results become abnormal vary from person to person. Laboratory tests are particularly useful in settings where cooperativeness is suspected or when a history is not available. Several biochemical and hematological tests, such as γ-glutamyltransferase (GGT) activity, aspartate aminotransferase (AST) activity, high-density lipoprotein cholesterol (HDL-C) content of serum, and erythrocyte mean corpuscular volume (MCV) are established markers of alcohol intake. Their validity as markers is based largely on correlations with recent intake at a single time point and on decreases in elevated values when heavy drinkers abstain from alcohol. These readily available laboratory tests provide important prognostic information and should be integral part of the assessment of persons with hazardous alcohol consumption. There are several other markers with considerable potential for more accurate reflection of recent alcohol intake. These include carbohydrate deficient transferrin, ß-hexosaminidase, acetaldehyde adducts and the urinary ratio of serotonin metabolites, 5-hydroxytryptophol and 5-hydroxyindoleacetic acid. These markers provide hope for more sensitive and specific aids to diagnosis and improved monitoring for intake.

Response of regional brain glutamate transaminases of rat to aluminum in protein malnutrition.

BACKGROUND: The mechanism of aluminum-induced neurotoxicity is not clear. The involvement of glutamate in the aluminium-induced neurocomplications has been suggested. Brain glutamate levels also found to be altered in protein malnutrition. Alterations in glutamate levels as well as glutamate-alpha-decarboxylase in different regions of rat brain has been reported in response to aluminum exposure. Thus the study of glutamate metabolising enzymes in different brain regions of rats maintained on either normal or restricted protein diet may be of importance for understanding the neurotoxicity properties of aluminium. RESULTS: Dietary protein restrictions does not have an significant impact on regional aluminum content of the brain. The interaction of aluminum intoxication and protein restriction is significant in the thalamic area and the midbrain-hippocampal region in cases of glutamate oxaloacetate transaminase. In the case of glutamate pyruvate transaminase, this interaction is significant only in thalamic area. CONCLUSION: The metabolism of amino acids, as indicated by activities of specific transaminases, of brain is altered in response to aluminum exposure. These alterations are region specific and are dependent on dietary protein intake or manipulation of the brain amino acid homeostasis.

Aluminum: impacts and disease.

Aluminum is the most widely distributed metal in the environment and is extensively used in modern daily life. Aluminum enters into the body from the environment and from diet and medication. However, there is no known physiological role for aluminum within the body and hence this metal may produce adverse physiological effects. The impact of aluminum on neural tissues is well reported but studies on extraneural tissues are not well summarized. In this review, the impacts of aluminum on humans and its impact on major physiological systems are summarized and discussed. The neuropathologies associated with high brain aluminum levels, including structural, biochemical, and neurobehavioral changes, have been summarized. In addition, the impact of aluminum on the musculoskeletal system, respiratory system, cardiovascular system, hepatobiliary system, endocrine system, urinary system, and reproductive system are discussed.