Search

Objective: To assess health-related quality of life and associated factors in patients treated with atypical antipsychotics, as well as to determine utility values using the EuroQol-5D-3L instrument. Methods: A cross-sectional study was conducted at a state-run pharmacy in the Brazilian National Health System. Individuals were included if they were using a single atypical antipsychotic and completed the EuroQol-5D-3L. Sociodemographic, behavioral, and clinical data were collected. The dependent variable was the EuroQol-5D-3L utility score. Associations between the independent variables and the dependent variable were analyzed in a multiple linear regression model. Results: A total of 394 patients were included, and their mean utility score was 0.664±0.232. Patients treated with clozapine had the highest mean score (0.762 [0.202]), followed by olanzapine (0.687 [0.230]), risperidone (0.630 [0.252]), ziprasidone (0.622 [0.234]), and quetiapine (0.620 [0.243]). The following variables were related to higher utility scores: income, employment, clozapine use, no illicit psychoactive substance use, no suicide attempts, and no comorbidities. Conclusion: Evaluating health-related quality of life differences in the available atypical antipsychotics can facilitate the choice of treatment, improve health outcomes, and ensure rational prescriptions.

A região Norte de Minas possui a produção de leite limitada, principalmente em função da seca, no entanto, esta é a base econômica da agricultura familiar que sustenta a região. Assim, realizou-se um estudo com o objetivo de avaliar o efeito do ambiente térmico sobre as respostas fisiológicas de vacas ¾ Holandês-Zebu, na região do semiárido mineiro a fim de se verificar a adaptabilidade destes animais. O experimento foi conduzido no verão e inverno, na fazenda Bela Vista localizada no município de Verdelândia (MG), onde foram avaliadas 10 vacas ¾ Holandês x Zebu (HxZ), em cada época. O ambiente térmico foi caracterizado por meio de medições diárias da temperatura do ar, umidade relativa do ar, índice de temperatura de globo e umidade e carga térmica radiante. Os parâmetros fisiológicos: frequência respiratória e cardíaca, temperatura de superfície corporal e temperatura retal, espessura, cor e densidade do pelame, e comprimento dos pelos foram mensurados antes da ordenha matutina, em função das estações do ano, diariamente, durante 15 dias. As variáveis e índices climáticos foram superiores no verão e no período da tarde. A frequência respiratória e a espessura do pelame não diferiram estatisticamente, no entanto as demais variáveis foram superiores no verão. As variáveis climáticas induziram diferenças nos parâmetros fisiológicos, mas foram assimiladas pelos animais, o que permite concluir que as vacas ¾ HxZ adaptam-se ao clima do semiárido mineiro sem manifestarem situação de estresse térmico.

Objective: Analyze the factors associated with the occurrence of falls in the elderly with low bone mineral density. Methods: Study performed between July 2014 and January 2016. Involved a cross sectional secondary data collection and telephone survey to counterreferred elderly patients from a secondary care service for primary care service in Belo Horizonte, Minas Gerais. Results: Were analyzed data from 2.020 patients and, among them, 1.120 were selected to participation in telephone survey phase. Respondents were predominantly female, aged 70-79 years, with normal or overweight body mass index, diagnosed with osteoporosis and family history of fractures. Regarding habits, the greater proportion did not practice physical activities, did not drink and smoke, did not sunbathe and had low intake of dark green vegetables. In addition, most of them had a fixed income, had been contacted by primary care after counterreferral and depended exclusively on the National Unified Health System. Higher proportion of falls was observed among women, in patients diagnosed with osteoporosis, with advanced age, who did not receive contact to return to the health center and in those with individual and family history of fractures. Statistical analysis demonstrate female gender, advanced age, individual or family history of fractures and low or no intake of dark green vegetables were factors that increased the risk of falls. Conclusion: Recommendations for improving health habits are simple actions and should be encouraged because they contribute to reducing the occurrence of falls and, consequently, it may lead to decrease morbidity and mortality of elderly patients.

Capsicum baccatum is one of the main pepper species grown and consumed in South America. In Brazil, it is commonly cultivated by family farmers, using mostly the genotypes bishop's hat genotypes (locally cambuci) and red chili pepper (dedo-de-moça). This study had the objective of characterizing 116 C. baccatum accessions from different regions of Brazil, based on morphological fruit descriptors and AFLP (Amplified Fragment Length Polymorphisms) markers. Broad phenotypic variability among the C. baccatum accessions was detected when using morphological fruit descriptors. The Ward modified location model (Ward-MLM) discriminated five groups, based mainly on fruit shape. Six combinations of AFLP primers detected polymorphism in 97.93% of the 2466 identified bands, indicating the high genetic variability in the accessions. The UPGMA coincided with the Bayesian clustering analysis and three large groups were formed, separating the wild variety C. baccatum var. praetermissum from the other accessions. There was no relation between genetic distance and geographical origin of the accessions, probably due to the intense exchange of fruits and seeds between farmers. Morphological descriptors used together with AFLP markers proved efficient in detecting the levels of genetic variability among the accessions maintained in the germplasm collections. These results can be used as an additional source of helpful information to be exploited in C. baccatum breeding programs.

Parapiptadenia rigida is a tropical early secondary succession tree characteristic of the Tropical Atlantic Rainforest. This species is of great ecological importance in the recovery of degraded areas. In this study we investigated the variability and population genetic structure of eight populations of P. rigida. Five AFLP primer combinations were used in a sample of 159 individuals representing these eight populations, rendering a total of 126 polymorphic fragments. The averages of percentage of polymorphic loci, gene diversity, and Shannon index were 60.45%, 0.217, and 0.322, respectively. A significant correlation between the population genetic variability and the population sizes was observed. The genetic variability within populations (72.20%) was higher than between these (22.80%). No perfect correlation was observed between geographic and genetic distances, which might be explained by differences in deforestation intensities that occurred in these areas. A dendrogram constructed by the UPGMA method revealed the formation of two clusters, these also confirmed by Bayesian analysis for the number of K cluster. These results show that it is necessary to develop urgent management strategies for the conservation of certain populations of P. rigida, while other populations still preserve reasonably high levels of genetic variability.

We isolated and characterized eleven polymorphic microsatellite loci for Aegiphila sellowiana an outcrossing pioneer tree species that is frequently used in reforestation programs of tropical riparian forests in Brazil. A total of 38 alleles were detected across a sample of 45 individuals of A. sellowiana, with an average number of 3.45 alleles per locus. The average polymorphic information content (PIC) was 0.430 and the observed (HO) and expected (HE) heterozygosity values varied from 0.156 to 1.000 and 0.145 to 0.730, respectively. Eight loci exhibited significant deviation from Hardy-Weinberg equilibrium (P ≤ 0.001) and 32 pair combinations of loci showed significant linkage disequilibrium (P ≤ 0.001). All 11 primers were tested for cross amplification in 12 species belonging to the family Lamiaceae and 5 species belonging to the related family Verbenaceae. The sequence and diversity information obtained using these microsatellites and their cross-transferability to other species of Lamiaceae as well as Verbenaceae will increase our understanding of genetic structures and species relationships within Aegiphyla and other genera of these families.

The genetic relationships among 81 maize accessions consisting 79 landraces and two improved varieties, maintained by farmers in southern Brazil were investigated using Random Amplified Polymorphic DNA (RAPD). Thirty-two highly informative primers amplified 255 markers of which 184 (72.2%) were polymorphics. Based on the RAPD markers, a dendrogram was constructed using the UPGMA method. The range of genetic similarity was from 0.78 to 0.91. The molecular data grouped the accessions into two main clusters, which were correlated according to kernel colors. Small clusters were seen associated to characteristics, such as kernel morphology. The analysis of the molecular data revealed that maize management adopted by small-scale farmers has contributed to the maintenance of genetic variability and since field isolation is a regular practice, variety identities have been preserved. These results will be useful to establish and maintain a germplasm collection of landrace maize and may guide us in designing strategies that maximize the utility of maize genetic resources.

Inter-simple sequence repeat (ISSR) markers were used to evaluate genetic divergence among eight Coffea species and to identify the parentage of six interspecific hybrids. A total of 14 primers which contained different simple sequence repeats (SSR) were used as single primers or combined in pairs and tested for PCR amplifications. Two hundred and thirty highly reproducible fragments were amplified, which were then used to estimate the genetic similarity and to cluster the Coffea species and hybrids. High levels of interspecific genetic variation were revealed. The dinucleotide motif (GA)9T combined with other di- tri- and tetra-nucleotides produced a greater number of DNA fragments, mostly polymorphics, suggesting a high frequency of the poly GA microsatellite motifs in the Coffea genomes. The genetic similarity ranged from 0.25 between C. racemosa and C. liberica var. dewevrei to 0.86 between C. arabica var. arabica and Hybrid N. 2. The C. arabica species shared most of its markers with five of the six hybrids suggesting that it is the most likely candidate as one of the progenitors of those hybrids. These results revealed that ISSR markers could be efficiently used for genetic differentiation of the Coffea species and to identify the parentage of Coffea interspecific hybrids.

MEN2A is an autossomal dominant cancer syndrome characterised by the presence of medullary thyroid cancer, pheochromocytoma and primary hyperparathyroidism. Germline mutations of the RET protooncogene constitute the molecular defect and can be identified in affected individuals. Genetic screening of family members at risk allows early diagnosis and preventive measures before the appearance of the disease. We present a family with several members affected with MEN2A, their molecular characterisation and the clinical implications of genetic testing.We studied 18 members distributed among three generations of a family of which four members were clinically affected with MEN2A and cutaneous lichen amyloidosis. RET gene mutations were screened for in affected individuals and their offspring by PCR-RFLP techniques.Genetic testing revealed a point mutation at codon 634 (TGC>TGG), in the heterozygous state, in all affected individuals. The same mutation was also found in a five years old asymptomatic child which after total thyroidectomy showed to have multifocal medullary thyroid carcinoma.Genetic screening is the most suitable method for pre-symptomatic diagnosis of MEN2A allowing an efficient and early identification of individuals who will later develop the disease. These can be monitored more closely and be submitted to a prophylactic thyroidectomy before the appearance of medullary thyroid carcinoma. The ideal moment for this intervention is still under discussion although the results of this study suggest that it should be undertaken before the age of five.

To assess GH secretion in young adults treated with GH replacement therapy in childhood.From the 38 patients who concluded treatment with GH, we studied 20 (52.6%), 9 girls and 11 boys. Thirteen had Growth Hormone Deficiency (GHD)-65%, while 7 had Multiple Pituitary Hormone Deficiency (MPHD)-35%. The patients were retested within 6 months to 6 years after completing GH therapy. The mean age (+/- SD) at retesting was 18.1 +/- 2.6 years for those with GHD and 20.8 +/- 2.8 for those with MPHD. At reassessment we performed two provocative tests: insulin tolerance test (ITT) and clonidine test.Seven of the 20 patients retested, retained GH deficiency. Of the 13 patients with GHD, only one maintained the deficiency, while of the 7 patients with MPHD, 6 maintained the deficiency.Young adults with GH deficiency treated with this hormone should be retested in order to identify those who are truly GH insufficient adults and may benefit from replacement therapy.

A total of 618 patients with end-stage renal disease received kidney transplants between 1980 and September 1996. Twenty eight of them were diabetics. Better results were achieved for type 1 diabetic patients than for type 2 (mortality: 5.9% vs 27.3%; functioning graft: 88.2% vs 72.7%). The morbility was also higher in those patients (infections: 81.8% vs 29.4%; vascular complications: 45.5% vs 17.6%). Actuarial patient and graft survival were lower for type 2 than for non diabetic patients. For type 1 diabetics the results are similar to those for non diabetics. Better results can probably be achieved by restricting the selection criteria. The decision to transplant or maintain on dialysis should be made on a case by case basis.

To analyse the type and frequency of cranial CT and NMR imaging anomalies in children of short stature. Patients and Interventions: We studied 57 children of short stature with a mean age (+/-SD) of 10.1 +/- 3.8 years, 34 boys and 23 girls, all of them with auxometric criteria of GH deficiency. After studying the pituitary function and determination of karyotype in the girls, the children were classified in to five groups:-Isolated GHD (IGHD) (n = 32), multiple pituitary hormone deficiency (MPHD) (n = 6), neurosecretory dysfunction (NSD) (n = 8), Turner syndrome (n = 7) and idiopathic short stature (ISS) (n = 4). The imaging methods used were cranial CT or NMR.Of the 57 children studied the CT/NMR was abnormal in 37(64.9%) children. We found anomalies in 65.6% of IGHD patients, 62.5% of NSD patients, 100% of MPHD patients and 57.1% and 25% in the Turner s. patients and ISS patients respectively. The most frequent anomaly was hypoplastic pituitary found in 50% of IGHD patients, 37.5% of NSD patients and 33.3% of MPHD patients. None of the cases of Turner s. or ISS had hypoplastic pituitary. An empty sella was the second most frequent anomaly found in 7 patients (IGHD-3, MPHD-3, DNS-1). Of the 25 children in which NMR was performed, 8 had hypoplastic pituitary and stalk and 2 had interruption of the pituitary stalk and ectopic neurohypophysis.These results strengthen the necessity for CT/NMR imaging in children of short stature which, besides allowing identification of tumors, also permits the diagnosis of idiopathic GHD because of its frequent association with cranial imaging anomalies, mainly hypoplastic pituitary.

To estimate the prevalence of hypertension (HT) in a group of patients with acromegaly at the moment of diagnosis and after treatment.Fifty-seven patients, 43 females and 14 males with a mean age of 45.19 +/- 11.9 years were studied retrospectively. In the last visit 9 patients (15.7%) were in remission and 47 (84.2%) had active acromegaly. We considered hypertensive the patients with systolic BP > or = 140 and/or diastolic BP > or = 90 mmHg. Hypertension was classified in four stages:- mild, moderate, severe and very severe.The prevalence of hypertension at the moment of diagnosis was 35%. The hypertensive patients had a mean age of 51.75 +/- 9.3 years and normotensive patients 41.65 +/- 11.6 years (p < 0.001). In females the prevalence of HT was 27.9% and in males it was 57% (p = NS). In hypertensive patients (n = 20), the mean BP was 159 +/- 15 (syst.)/97.2 +/- 9.8 (diast.), 16 patients (80%) had mild to moderate HT and the remainder had severe (n = 2) and very severe (n=1) HT. In the last visit, 22.2% of patients were cured and 46.8% of those with active acromegaly were hypertensive. None of the patients cured and initially normotensive developed HT; among those that were hypertensive (n = 3), 2 remained hypertensive and 1 became normotensive. Among patients with active acromegaly and initially normotensive, 7 developed HT 4.85 +/- 2.03 years later; of those hypertensive at diagnosis (n = 16), only one became normotensive. The last case was 27 years old. The patients that remained hypertensive had a mean age of 53.8 +/- 6.85 years (41-62 years).The prevalence of hypertension at the moment of diagnosis was 35%, similar to the majority of studies published and higher than the general population. The hypertensive patients were significantly older the normotensive patients and most of them had mild to moderate HT. We observed an increase in the prevalence of HT over the years in the cases that maintained active acromegaly. In our series only one of the three patients cured became normotensive, therefore, we concluded that HT in acromegaly is frequently irreversible. The chances of normalization seems higher in younger patients and probably with a shorter duration of acromegaly.

The aim of the study was to assess, in patients with non insulin dependent diabetes mellitus (NIDDM), either with previous failure to sulphonylureas or insulin treated since the disease started, if the combination of gliclazide to insulin therapy might induce a reduction of daily insulin requirement. 30 caucasian type II patients used to self-monitoring (11 female, 19 male, mean age 55.78 +/- 8.07) with residual pancreatic function (glucagon induced C-peptide release = 1.01 +/- 0.70 microgram/ml) entered the study. 8 were excluded for non compliance or for high antiinsulin antibodies levels and 4 are still under study. Each patients was given, for 3 months, 240 mg of gliclazide in addition to usual daily dose of insulin. Data presented as mean +/- s.e.m. were analysed with analysis of variance (p less than 0.05). Mean initial values of main parameters were as follows: glycaemia 192.7 +/- 33.1 mg/100 ml, insulinaemia 9.5 +/- 4.5 microUI/ml, daily insulin requirements 33.11 +/- 10.47 U/d, HbA1 C 7.5 +/- 1.7%. Total cholesterol 240.1 +/- 52.2 mg/10 ml, triglycerides 120.6 +/- 60.3 mg/100 ml. After 3 months treatment significant reduction in mean daily insulin requirements (20.78 +/- 16.15 U/d) was observed. In 13 patients (72.2%) while keeping good metabolic control (HbA1 C 7.46 +/- 1.63), insulin therapy was reduced (9 patients) or even stopped (4 patients). In the other 5, insulin was maintained or slightly increased. The increase in glucagon induced C-peptide release (1.41 +/- 0.99 micrograms/ml) did not reach significance, while glycaemia and insulinaemia were not changed (196.0 +/- 34.1 mg/100 ml, 11.02 +/- 5.05 microUI/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract  This paper deals with the local study of invariants of analytic curve singularities. For monomial curves we obtain a numerical description of the $${\mathcal{A}}_e$$ -codimension of parametrized curves in terms of classical invariants of the theory of curves, like the delta invariant, the Tjurina number and the Cohen-Macaulay type of its local ring. [ABSTRACT FROM AUTHOR]

The concept of water as a necessary and indispensable commodity is permanent, but its symbolic value has evolved to a certain extent throughout the ages. Its heritage from the past is as a commodity supplied by nature and found in nature. This is a primary statement without any bearing on the ecological positions subsisting in some sectors and strata of society. It is characterized by the concept of water as auniversal, necessary and indispensable commodity. [ABSTRACT FROM AUTHOR]

The Musa Germplasm Information System (MGIS) stands as a pivotal database for managing global banana genetic resources information. In our latest effort, we have expanded MGIS to incorporate in situ observations. We thus incorporated more than 3000 in situ observations from 133 countries primarily sourced from iNaturalist, GBIF, Flickr, Pl@ntNet, Google Street view and expert curation of the literature. This addition provides a more comprehensive and detailed view of banana diversity and its distribution. Additional graphical interfaces, supported by new Drupal modules, were developed, allowing users to compare banana accessions and explore them based on various filters including taxonomy and geographic location. The integrated maps present a unified view, showcasing both in situ observations and the collecting locations of accessions held in germplasm collections. This enhancement not only broadens the scope of MGIS but also promotes a collaborative and open approach in documenting banana diversity, to allow more effective conservation and use of banana germplasm. Furthermore, this work documents a citizen-science approach that could be relevant for other communities. Database URL: https://www.crop-diversity.org/mgis/musa-in-situ., (© The Author(s) 2024. Published by Oxford University Press.)

Crop landraces have unique local agroecological and societal functions and offer important genetic resources for plant breeding. Recognition of the value of landrace diversity and concern about its erosion on farms have led to sustained efforts to establish ex situ collections worldwide. The degree to which these efforts have succeeded in conserving landraces has not been comprehensively assessed. Here we modelled the potential distributions of eco-geographically distinguishable groups of landraces of 25 cereal, pulse and starchy root/tuber/fruit crops within their geographic regions of diversity. We then analysed the extent to which these landrace groups are represented in genebank collections, using geographic and ecological coverage metrics as a proxy for genetic diversity. We find that ex situ conservation of landrace groups is currently moderately comprehensive on average, with substantial variation among crops; a mean of 63% ± 12.6% of distributions is currently represented in genebanks. Breadfruit, bananas and plantains, lentils, common beans, chickpeas, barley and bread wheat landrace groups are among the most fully represented, whereas the largest conservation gaps persist for pearl millet, yams, finger millet, groundnut, potatoes and peas. Geographic regions prioritized for further collection of landrace groups for ex situ conservation include South Asia, the Mediterranean and West Asia, Mesoamerica, sub-Saharan Africa, the Andean mountains of South America and Central to East Asia. With further progress to fill these gaps, a high degree of representation of landrace group diversity in genebanks is feasible globally, thus fulfilling international targets for their ex situ conservation., (© 2022. The Author(s).)

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.

Activation of the egg by the sperm is the first, vital stage of embryogenesis. The sperm protein PLCζ has been proposed as the physiological agent that triggers the Ca 2+ oscillations that normally initiate embryogenesis. Consistent with this, recombinant PLCζ induces Ca 2+ oscillations in eggs and debilitating mutations in the PLCZ1 gene are associated with infertility in men. However, there has been no evidence that knockout of the gene encoding PLCζ abolishes the ability of sperm to induce Ca 2+ oscillations in eggs. Here, we show that sperm derived from Plcz1 -/- male mice fail to trigger Ca 2+ oscillations in eggs, cause polyspermy and thus demonstrate that PLCζ is the physiological trigger of these Ca 2+ oscillations. Remarkably, some eggs fertilized by PLCζ-null sperm can develop, albeit at greatly reduced efficiency, and after a significant time-delay. In addition, Plcz1 -/- males are subfertile but not sterile, suggesting that in the absence of PLCζ, spontaneous egg activation can eventually occur via an alternative route. This is the first demonstration that in vivo fertilization without the normal physiological trigger of egg activation can result in offspring. PLCζ-null sperm now make it possible to resolve long-standing questions in fertilization biology, and to test the efficacy and safety of procedures used to treat human infertility., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR) are Ca 2+ -mobilizing messengers important for modulating cardiac excitation-contraction coupling and pathophysiology. CD38, which belongs to the ADP-ribosyl cyclase family, catalyzes synthesis of both NAADP and cADPR in vitro However, it remains unclear whether this is the main enzyme for their production under physiological conditions. Here we show that membrane fractions from WT but not CD38 -/- mouse hearts supported NAADP and cADPR synthesis. Membrane permeabilization of cardiac myocytes with saponin and/or Triton X-100 increased NAADP synthesis, indicating that intracellular CD38 contributes to NAADP production. The permeabilization also permitted immunostaining of CD38, with a striated pattern in WT myocytes, whereas CD38 -/- myocytes and nonpermeabilized WT myocytes showed little or no staining, without striation. A component of β-adrenoreceptor signaling in the heart involves NAADP and lysosomes. Accordingly, in the presence of isoproterenol, Ca 2+ transients and contraction amplitudes were smaller in CD38 -/- myocytes than in the WT. In addition, suppressing lysosomal function with bafilomycin A1 reduced the isoproterenol-induced increase in Ca 2+ transients in cardiac myocytes from WT but not CD38 -/- mice. Whole hearts isolated from CD38 -/- mice and exposed to isoproterenol showed reduced arrhythmias. SAN4825, an ADP-ribosyl cyclase inhibitor that reduces cADPR and NAADP synthesis in mouse membrane fractions, was shown to bind to CD38 in docking simulations and reduced the isoproterenol-induced arrhythmias in WT hearts. These observations support generation of NAADP and cADPR by intracellular CD38, which contributes to effects of β-adrenoreceptor stimulation to increase both Ca 2+ transients and the tendency to disturb heart rhythm., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Database Url: https://www.crop-diversity.org/mgis/., (© The Author(s) 2017. Published by Oxford University Press.)

Spontaneous Ca 2+ waves, also termed store-overload-induced Ca 2+ release (SOICR), in cardiac cells can trigger ventricular arrhythmias especially in failing hearts. SOICR occurs when RyRs are activated by an increase in sarcoplasmic reticulum (SR) luminal Ca 2+ . Carvedilol is one of the most effective drugs for preventing arrhythmias in patients with heart failure. Furthermore, carvedilol analogues with minimal β-blocking activity also block SOICR showing that SOICR-inhibiting activity is distinct from that for β-block. We show here that carvedilol is a potent inhibitor of cADPR-induced Ca 2+ release in sea urchin egg homogenate. In addition, the carvedilol analog VK-II-86 with minimal β-blocking activity also suppresses cADPR-induced Ca 2+ release. Carvedilol appeared to be a non-competitive antagonist of cADPR and could also suppress Ca 2+ release by caffeine. These results are consistent with cADPR releasing Ca 2+ in sea urchin eggs by sensitizing RyRs to Ca 2+ involving a luminal Ca 2+ activation mechanism. In addition to action on the RyR, we also observed inhibition of inositol 1,4,5-trisphosphate (IP 3 )-induced Ca 2+ release by carvedilol suggesting a common mechanism between these evolutionarily related and conserved Ca 2+ release channels.