Macelignan inhibits bee pathogenic fungi Ascophaera apis growth through HOG1 pathway.

Ascosphaera apis is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility in vitro against A. apis and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC) assay and western blot analysis. Macelignan had 1.56 and 3.125 µg/mL MIC against A. apis after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against A. apis among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O-ß-D-glucopyranoside). Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including A. apis, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat A. apis, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-A. apis activity by inhibiting phosphorylation using S. cerevisiae as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against A. apis infection in bees.

Macelignan inhibits bee pathogenic fungi Ascophaera apis growth through HOG1 pathway

Ascosphaera apis is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility in vitro against A. apis and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC) assay and western blot analysis. Macelignan had 1.56 and 3.125 μg/mL MIC against A. apis after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against A. apis among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O-β-D-glucopyranoside). Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including A. apis, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat A. apis, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-A. apis activity by inhibiting phosphorylation using S. cerevisiae as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against A. apis infection in bees.

Using death certificates to characterize sudden infant death syndrome (SIDS): opportunities and limitations.

OBJECTIVE: To examine cause-of-death terminology written on death certificates for sudden infant death syndrome (SIDS) and to determine the adequacy of this text data in more fully describing circumstances potentially contributing to SIDS deaths. STUDY DESIGN: With 2003 and 2004 US mortality files, we analyzed all deaths that were assigned the underlying cause-of-death code for SIDS (R95). With the terminology written on the death certificates, we grouped cases into SIDS-related cause-of-death subcategories and then assessed the percentage of cases in each subcategory with contributory or possibly causal factors described on the certificate. RESULTS: Of the 4408 SIDS-coded deaths, we subcategorized 67.2% as "SIDS" and 11.0% as "sudden unexplained (or unexpected) infant death." The terms "probable SIDS" (2.8%) and "consistent with SIDS" (4.6%) were found less frequently. Of those death certificates that described additional factors, "bedsharing or unsafe sleep environment" was mentioned approximately 80% of the time. Most records (79.4%) did not mention any additional factors. CONCLUSION: Our death certificate analysis of the cause-of-death terminology provided a unique opportunity to more accurately characterize SIDS-coded deaths. However, the death certificate was still limited in its ability to more fully describe the circumstances leading to SIDS death, indicating the need for a more comprehensive source of SIDS data, such as a case registry.

Dimensions of child punishment in two Central American countries: Guatemala and El Salvador.

OBJECTIVE: Severe physical punishment of children is an important issue in international child health and welfare. This study examines such punishment in Guatemala and El Salvador. METHODS: Data came from nationally representative surveys of women aged 15-49 and men aged 15-59 residing in Guatemala (2002) and El Salvador (2002-2003). The surveys included questions about punishment experienced during childhood, with response options ranging from verbal scolding to beating. In Guatemala, parents were asked how they disciplined their children; questions allowed them to compare how they were punished in their childhood with how they punished their own children. Bivariate and multivariate analyses are presented. RESULTS: In Guatemala, 35% of women and 46% of men reported being beaten as punishment in childhood; in El Salvador, the figures were 42% and 62%, respectively. In both countries, older participants were relatively more likely than younger participants to have been beaten as children. Witnessing familial violence was associated with an increased risk of being beaten in childhood. In Guatemala, having experienced physical punishment as a child increased the chance that parents would use physical punishment on their own children. Multivariate analyses revealed that women who were beaten in childhood were significantly more likely in both countries to be in a violent relationship. CONCLUSIONS: The use of beating to physically punish children is a common problem in Guatemala and El Salvador, with generational and intergenerational effects. Its negative and lingering effects necessitate the introduction of policies and programs to decrease this behavior.

Dimensions of child punishment in two Central American countries: Guatemala and El Salvador / Dimensiones del castigo infantil en dos países de América Central: Guatemala y El Salvador

OBJECTIVE: Severe physical punishment of children is an important issue in international child health and welfare. This study examines such punishment in Guatemala and El Salvador. METHODS: Data came from nationally representative surveys of women aged 15-49 and men aged 15-59 residing in Guatemala (2002) and El Salvador (2002-2003). The surveys included questions about punishment experienced during childhood, with response options ranging from verbal scolding to beating. In Guatemala, parents were asked how they disciplined their children; questions allowed them to compare how they were punished in their childhood with how they punished their own children. Bivariate and multivariate analyses are presented. RESULTS: In Guatemala, 35 percent of women and 46 percent of men reported being beaten as punishment in childhood; in El Salvador, the figures were 42 percent and 62 percent, respectively. In both countries, older participants were relatively more likely than younger participants to have been beaten as children. Witnessing familial violence was associated with an increased risk of being beaten in childhood. In Guatemala, having experienced physical punishment as a child increased the chance that parents would use physical punishment on their own children. Multivariate analyses revealed that women who were beaten in childhood were significantly more likely in both countries to be in a violent relationship. CONCLUSIONS: The use of beating to physically punish children is a common problem in Guatemala and El Salvador, with generational and intergenerational effects. Its negative and lingering effects necessitate the introduction of policies and programs to decrease this behavior.

OBJETIVOS: El castigo físico severo de niños es un tema importante de la salud y el bienestar infantil en el mundo. En el presente estudio se analiza este tipo de castigo en Guatemala y El Salvador. MÉTODOS: Se tomaron los datos de encuestas representativas nacionales realizadas a mujeres de 14 a 59 años y hombres de 15 a 59 años que residían en Guatemala (2002) y El Salvador (2002-2003). Las encuestas contenían preguntas sobre los castigos que sufrieron en su niñez, con posibilidades de respuesta que iban desde regaños verbales hasta golpizas. En Guatemala se preguntó a los padres cómo disciplinaban a sus hijos; las preguntas les permitían comparar cómo ellos eran castigados en su niñez y cómo ellos castigaban a sus hijos. Se presentan los resultados de los análisis bifactorial y multifactorial. RESULTADOS: En Guatemala, 35 por ciento de las mujeres y 46 por ciento de los hombres informaron haber sido golpeados como castigo durante su niñez; en El Salvador, las cifras fueron 42 por ciento y 62 por ciento, respectivamente. En ambos países, los encuestados más viejos tenían una mayor probabilidad de haber sido golpeados en su niñez que los encuestados más jóvenes. Haber presenciado violencia familiar se asoció con un incremento en el riesgo de recibir golpizas durante la niñez. En Guatemala, haber recibido castigos físicos durante la niñez aumentó la probabilidad de que como padres aplicaran castigos físicos a sus hijos. El análisis multifactorial reveló que las mujeres de ambos países golpeadas durante su niñez tenían significativamente más probabilidades de encontrarse en una relación violenta. CONCLUSIONES: El uso de golpes para castigar físicamente a niños es un problema frecuente en Guatemala y El Salvador, con efectos generacionales e intergeneracionales. Sus efectos prolongados y negativos requieren de la aplicación de políticas y programas que permitan reducir este comportamiento.

A cytotoxic diterpene from Alomia myriadenia.

An extract of the aerial parts from Alomia myriadenia Schultz-Bip. ex Baker (Asteraceae) showed significant cytotoxicity against a panel of human cancer cell lines in a screening of extracts from Brazilian Atlantic Forest plant species. Employing a bioassay-linked HPLC-electrospray/MS method, followed by semi-preparative HPLC, the active component was isolated and characterized as a mixture of epimers of the labdane diterpene 12S,16-dihydroxy-ent-labda-7,13-dien-15,16-olide.

A new mutation of the glucose-6-phosphatase gene in a 4-year-old girl with oligosymptomatic glycogen storage disease type 1a.

A 4-year-old German girl was diagnosed as having glycogen storage disease type la and showed no other marked symptoms except hepatomegaly. The glucose-6-phosphatase activity in the liver was approximately 1.5% to 5.0% of normal values, and molecular analysis revealed compound heterozygosity for R83C and the novel mutation N264K. This result indicates that there is a wide clinical variation of glucose-6-phosphatase deficiency. DNA analysis is helpful for confirmation of the diagnosis, as well as establishment of the genotype and phenotype correlation in glycogen storage disease type 1a.

Mutations in the galactose-1-phosphate uridyltransferase gene of two families with mild galactosaemia variants.

Classical galactosaemia, deficiency of galactose-1-phosphate uridyltransferase (GALT), is characterized by acute symptoms of hepatomegaly, jaundice, sepsis, cataracts and growth retardation. Treatment with dietary galactose restriction corrects these complications immediately; however, most of these children develop long-term complications of verbal dyspraxia, mental retardation and ovarian failure. Our previous molecular study showed that the most common mutation of the GALT gene is a missense mutation of Q188R (replacement of glutamine-188 by arginine) in approximately 60-65% of the German galactosaemic population. The coding region of GALT was amplified by the polymerase chain reaction from genomic DNA of classical galactosaemic individuals, who are negative or heterozygous for Q188R, and was further characterized by direct sequencing. Three new disease-causing mutations, two missense and a stop codon mutation, were identified in three patients from two families with mild galactosaemic variants: firstly R67C, replacement of arginine-67 by cysteine and W316X, the stop codon at tryptophan-316 in one male; secondly A330V, replacement of alanine-330 by valine in two female siblings. In the first family the patient was also heterozygous for the polymorphism N314D and in the second family both girls were compound heterozygotes for Q188R and A330V. All three galactosaemic individuals have a considerable amount of the residual GALT activity in RBC and the galactose-1-phosphate (GALP) level decreased much faster on treatment than that of other galactosaemic patients with missense mutations such as Q188R. The clinical and biochemical data of these patients were much more favourable in comparison with those of two female galactosaemic individuals, one homozygous for L195P and the other compound heterozygous for Q188R and L195P. These three missense mutations (R67C, L195P and A330V) also occur in highly conserved regions. These observations suggest that the phenotypic variation in galactosaemic individuals may be due to different molecular aetiologies.

Inhibition of lens-aldose reductase activity by brazilin and haematoxylin.

Brazilin and haematoxylin, plant pigments, were examined for their effects on the Bovine-Lens aldose reductase (LAR)-activity. About 50% inhibition was observed in a concentration of 10 (-4) M-brazilin and 10 (-4) M-haematoxylin, and above 95% inhibition was observed in a concentration of 10 (-3) M-brazilin and 10 (-3)M-haematoxylin. In order to determine the type of inhibition, kinetic studies were also conducted with brazilin and haematoxylin, in which both were found to be noncompetitive inhibitors.