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This study investigated factors that could be related to drinking water contamination in urban areas in order to obtain quality profiles that characterized presence of the glyphosate and nitrate contaminants. Thus, in a period of one year, 4,853 tap water samples from 89 cities in the northeastern region of the State of São Paulo, Brazil, were analyzed in 21 physicochemical and 2 microbiological parameters. Additionally, 4 demographic variables were also included in multivariate data analysis. Principal Component Analysis of physicochemical and microbiological data showed that glyphosate concentration is positively correlated with nitrate concentration, especially in cities that make exclusive use of groundwater, besides correlating with conductivity and with concentrations of calcium, magnesium, fluoride, chloride, phosphate and free residual chlorine. The inclusion of demographic variables in Principal Component Analysis did not significantly change waters physicochemical profiles, but in cities that exclusive use groundwater for public supply the number of hospitalizations for diarrhea correlated positively with glyphosate, nitrate and chloride concentrations, in addition to conductivity. Linear Discriminant Analysis models involving 5 variables (conductivity and concentrations of calcium, magnesium, chloride and nitrate) were able to predict the cities vulnerability to groundwater contamination by nitrate.

Background Sleep disturbance is a common psychiatric disorder in patients with cancer. However, many patients with incurable cancer have difficulty receiving oral administrations, which limits treatment options during disease progression. The aim of the present study was to assess the efficacy and safety of intravenous chlorpromazine treatment for sleep disturbances in patients with incurable cancer, with oral administration difficulty. Methods A prospective observational study was conducted among 52 patients with incurable cancer, with oral administration difficulty received daily intravenous chlorpromazine treatment for sleep disturbance from 2018 to 2020 at a single-unit university hospital. St. Mary's Hospital Sleep Questionnaire (SMHSQ) compared sleep before and after intravenous chlorpromazine administration. The primary endpoint was the efficacy rate of sleep quality [defined as a score of ≥4 (range: 1-6)] 7 days after receiving chlorpromazine. Results Beginning the day after receiving chlorpromazine, sleep quality significantly improved from a mean score of 1.6±0.7 to 4.3±1.2, and 80.8% [95% confidence interval (CI): 66.5-89.1%] and 69.2% (95% CI: 53.8-79.6%) of patients reported good sleep quality 3 and 7 days after receiving chlorpromazine, respectively. The patients reported increased total sleep time and fewer awakenings during sleep, and satisfaction with sleep and difficulty falling asleep improved. Some adverse events occurred [akathisia (n=2), dry mouth (n=2), and somnolence (n=3)]; all were Grade 1 (CTCAE ver5.0) and improved with chlorpromazine discontinuation. Systolic blood pressure and heart rate displayed no clinically problematic changes. Conclusions Intravenous chlorpromazine has a high tolerability and effectively treats sleep disturbances in patients with incurable cancer with oral administration difficulties.

Activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2 related factor 2 (Nrf2) system plays a role in repression of xenobiotic toxicity. The Coriandrum sativum L. leaf extract (CSLE) contains various aliphatic electrophiles such as (E)-2-decenal and (E)-2-dodecenal. In the present study, we examined the activation of Nrf2 coupled to chemical modification of Keap1 mediated by (E)-2-alkenals in CSLE, and the protective role of CSLE and (E)-2-alkenals against inorganic arsenite (iAsIII) cytotoxicity. Ultra-performance liquid chromatography-elevated collision energy mass spectrometry analysis revealed that (E)-2-decenal modified recombinant Keap1 at Cys241, Cys249, Cys257 and His274. Exposure of HepG2 cells to CSLE, (E)-2-decenal, or (E)-2-dodecenal upregulated Nrf2-related downstream signaling such as expression of phase-II xenobiotic-metabolizing enzymes and phase-III transporters involved in cytoprotection against iAsIII. Pretreatment with CSLE or (E)-2-butenal, a prototype of (E)-2-alkenal, prior to iAsIII exposure suppressed accumulation of iAsIII significantly and reduced iAsIII-induced cytotoxicity in cells. Oral administration of CSLE to C57BL/6 mice upregulated downstream proteins of Nrf2 and reduced accumulation of arsenic in liver tissue. The present study indicates that CSLE containing (E)-2-alkenals activates Nrf2, leading to a reduction in arsenic accumulation in vivo.

A new programme of general family and consumer science for all high school students that can contribute to career education was proposed. The programme had three sessions: ‘single life’, ‘family life’ and ‘retired life’ from the typical three main life stages. Students were challenged to think about their future with regard to real life issues such as housing, location, budgeting time and finances, and family issues. Students were able to consider their future life concretely and specifically from various viewpoints after taking part in this programme. Students also found value in home economics education in developing life skills and knowledge, in considering their actual life and in considering their future life.

The children's perception of dinner and dinner conversation with their parents was surveyed for sixth-grade students of elementary school in Japan. The data were analysed from the gender of children and attending parents. The children had dinner and dinner conversation more frequently with their mother than with their father. With father attendance, girls and boys had the same frequency of dinner and dinner conversation, although, with mother attendance, girls had dinner conversation more frequently than boys. Most of the children felt happy when they had dinner with their parents. However, a lower percentage of children felt happy when having dinner conversation with their parents, thought that they were important to their parents and thought dinner conversation was useful. More children felt happy during dinner and dinner conversation with their mother than with their father. However, there was no perceived difference in the usefulness of the conversation based on the father or the mother attending. The contents of conversation were greatly affected by which parent was attending. Subjects concerning children's manners were talked about more frequently in conversation with mothers than with fathers. Children had more frequent conversations with their father about ‘social issues’ and the ‘parents’ surroundings’ than with their mother. Girls had more frequent conversations on a wider variety of subjects with their mothers than boys. Girls could more easily share in their mothers’ knowledge or sense of values through dinner conversation. Boys were, for the most part, excluded from this process in conversation with either parent.

Previously, we established for the first time an in vivo monitoring assay system conjugated with random mutagenesis in order to study the structure-function relationship of the antimicrobial peptide, apidaecin [Taguchi et al. (1996) Appl. Environ. Microbiol. 62, 4652-4655]. In the present study, this methodology was used to carry out the functional mapping of a second target, thanatin, a 21-residue peptide that exhibits the broadest antimicrobial spectrum so far observed among insect defense peptides [Fehlbaum et al. (1996) Proc. Natl. Acad. Sci. USA 93, 1221-1225]. First, a synthetic gene encoding thanatin was expressed in a fused form with Streptomyces protease inhibitor protein, SSI, under the control of tac promoter in Escherichia coli JM109. Expression of the thanatin-fused protein was found to depend on the concentration of the transcriptional inducer, isopropyl-beta-D-thio-galactopyranoside (IPTG), and to parallel the degree of growth inhibition of the transformant cells. When a PCR random mutation was introduced into the structural gene for thanatin, diminished growth inhibition of the IPTG-induced transformed cells was mostly observed in variants as measured by colony size (plate assay) or optical density (liquid assay) in comparison with the wild-type peptide, possibly depending on the decreased antimicrobial activity of each variant. Next, wild-type thanatin and three variants screened by the in vivo assay, two singly mutated proteins (C11Y and M21R) and one doubly mutated protein (K17R/R20G), were stably overproduced with a fusion partner protein resulting in the efficient formation of inclusion bodies in E. coli BL21(DE3). The products were isolated in large amounts (yield 30%) from the fused protein by successive chemical and enzymatic digestions at the protein fusion linker site. Anti-E. coli JM109 activities, judged by minimum inhibitory concentration, of the purified peptides were in good agreement with those estimated semi-quantitatively by the in vivo assay. Based on the NMR solution structure and molecular dynamics, the structure-function relationship of thanatin is discussed by comparing the functional mapping data obtained here with the previous biochemical data. The functional mapping newly suggests the importance of a hydrogen bonding network formed within the C-terminal loop joining the beta-strands arranged antiparallel to one another that are supposed to be crutial for exhibiting anti-E. coli activity.

Glaucoma is a major cause of blindness characterized by progressive degeneration of the optic nerve and elevated intraocular pressure. Recent studies have revealed a genetic basis for a substantial proportion of cases of familial primary open-angle glaucoma (POAG) and the gene causing the abnormality has been identified. Sequence variations that meet the criteria for a probable disease-causing mutation have been found in the American and European populations. In this study, we examined 58 cases of sporadic glaucoma from Japan to clarify the relationship between the mutations of the GLC1A gene and sporadic glaucoma in Japan. We have examined 33 POAG, 17 primary closed-angle glaucomas, 6 normal-tension glaucomas and 2 steroid-induced glaucomas for mutation of the GLC1A gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct DNA sequencing studies. We identified a previously unreported GGT right curved arrow GAT transition at codon 451 in exon 3, resulting in a glycine to asparagine substitution in one POAG patient. No other mutations of the GLC1A gene were found in other types of glaucoma. These findings further emphasize the importance of GLC1A mutation in the development of POAG.

Background: Recent studies have revealed that administration of nitric oxide (NO) donors increases the release of neurotransmitters in various brain regions. In the retina, NO synthetase (NOS) is found in retinal amacrine and ganglion cells, and it is evident that NO is involved in encoding visual information. In the present study, therefore, NO donors were used to study the effect of exogenous NO on the high K+-evoked release of endogenous acetylcholine (ACh) in the rat retina. Methods: Isolated rat retinal preparations were superfused with modified Krebs-Ringer bicarbonate buffer solution. In each experiment, stimulation for 10 min with 30 mM KCl was done twice. The amounts of ACh released by the first or second KCl stimulation were termed S1 and S2 respectively. Test agents were applied just before the second KCl stimulation. The effects of test agents were evaluated as S2 divided by S1. ACh was converted to hydrogen peroxide and electrochemically assayed by high-performance liquid chromatography. Results: S-Nitro-N-acetyl-DL-penicillamine (SNAP), an NO donor, dose-dependently inhibited the high K+-evoked release of endogenous ACh. Such inhibition by NO was confirmed also by another NO donor, (±)-(E)-4-ethyl-2-[(E)-hydroxy imino]-5-nitro-3-hexenamide (NOR3). The inhibitory effect of SNAP was abolished by both carboxy-PTIO, an NO scavenger, and bicuculline, an antagonist of GABAA receptors. Conclusions: The NO-induced decrease of ACh release is probably due to an NO-induced increase of GABAergic system inhibition.

Background: Retinitis pigmentosa is a hereditary disease characterized by gradually developing degeneration of photoreceptors. The Royal College of Surgeons (RCS) rat is an experimental model of retinitis pigmentosa. However, there is a paucity of information concerning neurotransmitter contents in the retina of RCS rats. Thus, we determined the retinal contents of neurotransmitters in RCS rats at 4 and 23 weeks postnatally and in age-matched congenic control rats. Methods: Dopamine (DA) and acetylcholine (ACh) were electrochemically measured by high-performance liquid chromatography (HPLC). Neuroactive amino acids, including γ-aminobutyric acid (GABA) and taurine, were determined by means of an HPLC-precolumn derivatization method. Results: Contents of DA, ACh, glutamate, aspartate and GABA in the retina of RCS rats 4 weeks postnatally were within normal ranges. At 23 weeks, the retinal contents of DA, glutamate and aspartate in the RCS rats were significantly lower than in the age-matched control rats, while the contents of ACh and GABA were unaffected even at this later stage. On the other hand, the retinal content of glycine in the RCS rats at 23 weeks was significantly higher than that in the age-matched control rats. It is interesting to note that the content of taurine in the RCS rats had already decreased at 4 weeks postnatally and the decrease was more marked at 23 weeks. Conclusion: The decrease in taurine content is probably the first sign of degeneration revealed by the retinal neurotransmitters of RCS rats.

In this paper the electronic spreadsheets built in Microsoft ExcelR software are presented, and these parameters enable to estimate the decision limit (CCα) and the detection capability (CCβ) at the detection limit and of the maximum permitted value (MVP) regions. The estimates are evaluated from linear and homoscedastic analytical curves obtained in calibration procedures based on ISO standards and IUPAC guidelines. After validating by means of manual data processing, the electronic spreadsheets were used for determining the nitrite in bottled waters (MVP = 0.02 mg/L) and the fluoride contents in public supply waters (compliance interval = 0.6 to 0.8 mg/L). For fluoride analysis there are the minimum required value (0.6 mg/L) and the maximum acceptable value (0.8 mg/L) for its concentration; therefore, the spreadsheet computes the critical concentration at both limits with a probability of a type I error equal to 0.05. On that account, the electronic spreadsheets provide the rapid decision between compliant and non-compliant data in the interpretation of results.

We examined the properties of voltage-gated calcium channels mediating endogenous dopamine (DA) and acetylcholine (ACh) release in the isolated rat retina. Application of 30 mM KCl elicited the release of DA and ACh, and these releases were abolished in Ca(2+)-free medium. The high K(+)-evoked DA release was largely blocked by both of omega-agatoxin IVA and omega-conotoxin MVIIC, P- and Q-type calcium channel antagonists, and partly blocked by isradipine, and L-type calcium channel antagonist, and omega-conotoxin GVIA, an N-type calcium channel antagonist. omega-Agatoxin IVA at a small dose, sufficient to block P-type channels alone, was however without effect. On the other hand, the high K(+)-evoked ACh release was partly blocked by omega-agatoxin IVA and omega-conotoxin MVIIC, but was resistant to isradipine and omega-conotoxin GVIA. Flunarizine, a non-selective T-type calcium channel antagonist, did not inhibit the release of DA and ACh. Cd2+ markedly blocked the release of both DA and ACh, Co2+ and Ni2+ slightly blocked the release of DA, and the release of ACh was not blocked by these two divalent cations. These results suggest that the high K(+)-evoked release of retinal DA is largely mediated by omega-agatoxin IVA and omega-conotoxin MVIIC sensitive calcium channels (probably Q-type channels), while the release of retinal ACh is largely mediated by as yet uncharacterized Cd2+ sensitive calcium channels. The properties of voltage-gated calcium channels involved in the release of ACh in the rat retina differ from those of DA.