Measurement of Plasma Tryptophan Metabolites: Clinical and Experimental Application for Depression and Stress States Assessment

There are three pathways in tryptophan (TRP) metabolism. Serotonin (5-hydroxytryptamine; 5-HT) pathway is important in mood, anxiety, memory, and cognition and is impaired in depression. Kynurenine (KYN) pathways are involved in immunity, inflammation, muscles movement, and mental health. We investigated changes in TRP metabolites in plasmas of stressed rats and in depressive patients. TRP metabolite levels in 5-HT and KYN pathways in various brain areas and plasma were increased soon after electric foot shock given to rats but returned to normal 24 h later. Plasma levels of 5-HT were very low or undetectable in patients of monopolar depression. 5-hydroxyindole acetic acid (5-HIAA)/TRP ratios or KYN/TRP ratios were not different between healthy controls and depressive patients, indicating 5-HT quickly being degraded into 5-HIAA in patients of depression but KYN levels were not changed in depression. These results indicate that TRP metabolism changes upon stress application and in patients of depression

Studies on Tryptophan Metabolites in Patients of Major Monopolar Depression

Plasma levels of tryptophan metabolites were compared between healthy volunteers and patients of major monopolar depression at various ages and genders. An ultrahigh-speed liquid chromatography/mass spectrometry has been used for analysis. There are significant gender and age differences in TRP metabolites of healthy volunteers. At the upper stream of metabolism, metabolites of young women and old men are higher, but at the lower stream of metabolism, their levels are higher in young men and old women. Such differences disappear in plasma of patients of major monopolar depression except for kynurenine (KYN). Daily variation of blood serotonin (5-HT) levels showed that 5-HT levels were low in the morning and increased toward evening, but blood levels of 5-HT were higher in healthy people than depressive people in the morning and decreased to ward evening. Significant age and gender differences of plasma levels of tryptophan metabolites in healthy volunteers disappear in patients of major monopolar depression. Blood levels of 5-HT were higher in healthy people than depressive patients

Evaluation of recharge areas of Arusha Aquifer, Northern Tanzania: application of water isotope tracers

This research article published by IWA Publishing, 2020In Arusha urban, northern Tanzania, groundwater contributes about 80% of the water supply. However, elevated fluoride levels and evidence of anthropogenic pollution have been reported in the groundwater around Mount Meru which is a water source for Arusha urban. This study aims at understanding the recharge areas and flow pathways of groundwater in what has been a poorly monitored area. The study uses the isotopic ratio of oxygen and hydrogen to estimate the groundwater recharge area and flow pathway. The results show the recharge elevation of groundwater is between 1,800 and 3,500 m above mean sea level on the slopes of Mount Meru. The average fluoride contents in the study area are 5.3 ± 0.4 mg/L greater than the limits of 1.5 mg/L set by the World Health Organization (WHO) and Tanzania. The nitrate concentration of 83.9 mg/L at the lower elevation areas (<1,400 m above mean sea level) exceeds the 50 mg/L WHO limit. The relationship of F− with δ18O and NO3− suggests the leaching of fluoride in high altitudes and dilution in lower altitudes

Five-year follow-up of Japanese patients with Paget's disease of the bone after treatment with low-dose oral alendronate: a case series

<p>Abstract</p> <p>Introduction</p> <p>Paget's disease of the bone is characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton. Although this disease is rare in Japan, it is common in western and southern Europe, and among British migrants in Australia and New Zealand. Bisphosphonates have been widely used for the treatment of Paget's disease of the bone and are considered to be the treatment of choice. However, there have been few reports on the long-term follow-up examination of patients after their treatment with bisphosphonates.</p> <p>Case presentation</p> <p>We report the treatment with a low dose of oral alendronate (5 mg per day) which was effective in reducing bone turnover and pain over the five-year follow-up period in two Japanese patients, a 66-year-old man and a 68-year-old woman, with Paget's disease of the bone. Furthermore, in one patient, no clinical symptoms, such as bone pain or increases in serum total alkaline phosphatase and urinary N-terminal telopeptide of type I collagen as markers of bone turnover, were observed over the patient's five-year follow-up period.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first report of a long-term follow-up of patients with Paget's disease of the bone after a six-month treatment with low-dose oral alendronate (5 mg per day).</p

Validation of the physical and RBE-weighted dose estimator based on PHITS coupled with a microdosimetric kinetic model for proton therapy

The microdosimetric kinetic model (MKM) is widely used for estimating relative biological effectiveness (RBE)-weighted doses for various radiotherapies because it can determine the surviving fraction of irradiated cells based on only the lineal energy distribution, and it is independent of the radiation type and ion species. However, the applicability of the method to proton therapy has not yet been investigated thoroughly. In this study, we validated the RBE-weighted dose calculated by the MKM in tandem with the Monte Carlo code PHITS for proton therapy by considering the complete simulation geometry of the clinical proton beam line. The physical dose, lineal energy distribution, and RBE-weighted dose for a 155 MeV mono-energetic and spread-out Bragg peak (SOBP) beam of 60 mm width were evaluated. In estimating the physical dose, the calculated depth dose distribution by irradiating the mono-energetic beam using PHITS was consistent with the data measured by a diode detector. A maximum difference of 3.1% in the depth distribution was observed for the SOBP beam. In the RBE-weighted dose validation, the calculated lineal energy distributions generally agreed well with the published measurement data. The calculated and measured RBE-weighted doses were in excellent agreement, except at the Bragg peak region of the mono-energetic beam, where the calculation overestimated the measured data by ~15%. This research has provided a computational microdosimetric approach based on a combination of PHITS and MKM for typical clinical proton beams. The developed RBE-estimator function has potential application in the treatment planning system for various radiotherapies

The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes

A failing heart shows severe energy insufficiency, and it is presumed that this energy shortage plays a critical role in the development of cardiac dysfunction. However, little is known about the mechanisms that cause energy metabolic alterations in the failing heart. Here, we show that the novel RING-finger protein 207 (RNF207), which is specifically expressed in the heart, plays a role in cardiac energy metabolism. Depletion of RNF207 in neonatal rat cardiomyocytes (NRCs) leads to a reduced cellular concentration of adenosine triphosphate (ATP) and mitochondrial dysfunction. Consistent with this result, we observed here that the expression of RNF207 was significantly reduced in mice with common cardiac diseases including heart failure. Intriguingly, proteomic approaches revealed that RNF207 interacts with the voltage-dependent anion channel (VDAC), which is considered to be a key regulator of mitochondria function, as an RNF207-interacting protein. Our findings indicate that RNF207 is involved in ATP production by cardiomyocytes, suggesting that RNF207 plays an important role in the development of heart failure