Vanadium in Bipolar Disorders-Reviving an Old Hypothesis.

Bipolar disorder (BD) is a severe and common chronic mental illness. The biological basis of the disease is poorly understood and its treatment is unsatisfactory. Our previous studies supported the notion that alterations in Na+, K+-ATPase activity were involved in the etiology of BD. As various chemical elements inhibit Na+, K+-ATPase, we determined the concentration of 26 elements in the serum of BD patients before and after treatment and in postmortem brain samples from BD patients, and compared them with matched controls. The only element that was reduced significantly in the serum following treatment was vanadium (V). Furthermore, the concentration of V was significantly lower in the pre-frontal cortex of BD patients compared with that of the controls. Intracerebroventricular administration of V in mice elicited anxiolytic and depressive activities, concomitantly inhibited brain Na+, K+-ATPase activity, and increased extracellular signal-regulated kinase phosphorylation. A hypothesis associating V with BD was set forth decades ago but eventually faded out. Our results are in accord with the hypothesis and advocate for a thorough examination of the possible involvement of chemical elements, V in particular, in BD.

Chemical Element Profiling in the Sera and Brain of Bipolar Disorders Patients and Healthy Controls.

Bipolar Disorder (BD) is a severe recurrent affective mood disorder characterized by a wide range of lifelong mood swings, varying between depressive and manic states. BD affects more than 1% of the world's population irrespective of nationality, ethnic origin, or socioeconomic status and is one of the main causes of disability among young people, leading to cognitive and functional impairment and raised mortality, particularly death by suicide. Trace elements play a vital role in many biochemical and physiological processes. Compelling evidence shows that element toxicity might play a crucial role in the onset and progression of neurodegenerative disorders, but their involvement in mood disorders has been scarcely studied. In the present investigation, we determined the concentration of 26 elements in the serum of BD patients before and after treatment and in postmortem brain samples from BD patients and compared them with matched controls. The only element that was reduced significantly in the serum following treatment was vanadium (V). Furthermore, the concentration of Al, B, Cu, K, Mg and V were significantly lower in the pre-frontal cortex of BD patients compared with those of the controls. A comparison of Spearman's rank correlation coefficients between the elements in the serum and brain of BD patients and control groups pointed to boron and aluminum as being involved in the disease. These results suggest that there is a disturbance in the elements' homeostasis and the inter-elements' relationship in the brain of BD patients and advocate a thorough examination of the possible involvement of chemical elements in different stages of the disease.

Lead in Archeological Human Bones Reflecting Historical Changes in Lead Production.

Forty years ago, in a seminal paper published in Science, Settle and Patterson used archeological and historical data to estimate the rates of worldwide lead production since the discovery of cupellation, approximately 5000 years ago. Here, we record actual lead exposure of a human population by direct measurements of the concentrations of lead in petrous bones of individuals representing approximately 12 000 years of inhabitation in Italy. This documentation of lead pollution throughout human history indicates that, remarkably, much of the estimated dynamics in lead production is replicated in human exposure. Thus, lead pollution in humans has closely followed anthropogenic lead production. This observation raises concerns that the forecasted increase in the production of lead and other metals might affect human health in the near future.

Exposure to metals and morbidity at eight years follow-up in women of childbearing age.

This exploratory study was aimed to investigate the link between toxic metal content in women's urine and their morbidity 2 years before and 6 years after the test. Concentrations of 25 metals in urine were analyzed for 111 pregnant women collected prior to delivery. All women were of Arab-Bedouin origin. Information on primary care and hospital visits during the study period was obtained. In a Poisson regression model, a health outcome was regressed over metal exposure and other factors. A Weighted Quantile Sum Regression (WQS) approach was used to indicate metals dominating in their possible impact on women's morbidity. Obesity was the most frequently diagnosed condition in this population (27.9%). Diagnoses in a neurological category accounted for 36.0%, asthma or respiratory-25.2%, psychiatric-12.6%, cardiovascular-14.4% and cancer or benign growth-for 13.5%. Based on WQS analysis, cancer and benign growth were mostly attributed to the increased levels of cadmium, cardiovascular outcomes were linked with lead, and obesity was found associated with elevated levels of nickel. Hematological, neurological and respiratory outcomes were attributed to multiple non-essential metals. The health and exposure profile of women in the study warrants a periodic biomonitoring in attempt to identify and reduce exposure to potentially dangerous elements.

Maternal metal concentration during gestation and pediatric morbidity in children: an exploratory analysis.

BACKGROUND: The majority of studies linking exposure to metals with certain health outcomes focus on known toxic metals. Alternatively, this study assesses the extent to which exposure to a wider range of metals during gestation is associated with childhood morbidity. METHODS: We analyzed the concentrations of 25 metals found in urine samples of 111 pregnant women of Arab-Bedouin origin collected prior to birth. In addition, we collected medical records on their offspring for six years following birth, including every interaction with HMOs, local hospitals, and pharmacies. RESULTS: The main types of morbidities diagnosed and treated during this period were preterm births, malformations, asthma-like morbidity, cardiovascular and behavioral problems, and obesity. Multivariable analysis showed that offspring born before term were more likely to have been exposed to elevated maternal concentrations of zinc, thallium, aluminum, manganese, and uranium, all with adjusted relative risk above 1.40 for an increase by each quintile. Likewise, children with asthma had been exposed to higher levels of magnesium, strontium, and barium at gestation, while behavioral outcomes were associated with elevated biometals, i.e., sodium, magnesium, calcium, selenium, and zinc, as well as higher levels of lithium, cobalt, nickel, strontium, cadmium, vanadium, arsenic, and molybdenum. A heatmap of adjusted relative risk estimates indicates the considerable implications that exposure to metals may have for preterm birth and developmental outcomes. CONCLUSIONS: The current study shows that perinatal exposure to metals is adversely associated with pediatric morbidity. Further such analyses on additional samples are warranted.

Ancient technology and punctuated change: Detecting the emergence of the Edomite Kingdom in the Southern Levant.

While the punctuated equilibrium model has been employed in paleontological and archaeological research, it has rarely been applied for technological and social evolution in the Holocene. Using metallurgical technologies from the Wadi Arabah (Jordan/Israel) as a case study, we demonstrate a gradual technological development (13th-10th c. BCE) followed by a human agency-triggered punctuated "leap" (late-10th c. BCE) simultaneously across the entire region (an area of ~2000 km2). Here, we present an unparalleled, diachronic archaeometallurgical dataset focusing on elemental analysis of dozens of well-dated slag samples. Based on the results, we suggest punctuated equilibrium provides an innovative theoretical model for exploring ancient technological changes in relation to larger sociopolitical conditions-in the case at hand the emergence of biblical Edom-, exemplifying its potential for more general cross-cultural applications.

Lead isotopes in silver reveal earliest Phoenician quest for metals in the west Mediterranean.

When and why did the Phoenicians initiate long-term connections between the Levant and western Europe? This is one of the most hotly debated questions in ancient Mediterranean history and cultural research. In this study, we use silver to answer this question, presenting the largest dataset of chemical and isotopic analyses of silver items from silver hoards found in Phoenician homeland sites. Intertwining lead isotope analysis of silver items with precise archaeological context and chronology, we provide analytical evidence for the onset of Phoenician westward expansion. We suggest that the quest for silver instigated a long, exploratory phase, first in Anatolia (Asia Minor) and Sardinia, and subsequently in the Iberian Peninsula. This phase preceded the establishment of sustainable, flourishing Phoenician colonies in the West by over a century. In so doing, our results buttress the "precolonization" theory, accord it a firm chronological framework, and demonstrate that the quest for silver (and probably other metals) was an incentive for Phoenician westward expansion. Furthermore, our results show that the Phoenicians introduced innovative silver production methods to historic Europe.

The Earliest Lead Object in the Levant.

In the deepest section of a large complex cave in the northern Negev desert, Israel, a bi-conical lead object was found logged onto a wooden shaft. Associated material remains and radiocarbon dating of the shaft place the object within the Late Chalcolithic period, at the late 5th millennium BCE. Based on chemical and lead isotope analysis, we show that this unique object was made of almost pure metallic lead, likely smelted from lead ores originating in the Taurus range in Anatolia. Either the finished object, or the raw material, was brought to the southern Levant, adding another major component to the already-rich Late Chalcolithic metallurgical corpus known to-date. The paper also discusses possible uses of the object, suggesting that it may have been used as a spindle whorl, at least towards its deposition.