Biallelic gephyrin variants lead to impaired GABAergic inhibition in a patient with developmental and epileptic encephalopathy.

Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition is linked to epilepsy. Gephyrin (Geph) is the principal scaffolding protein at inhibitory synapses and is essential for postsynaptic clustering of glycine (GlyRs) and GABA type A receptors. Consequently, gephyrin is crucial for maintaining the relationship between excitation and inhibition in normal brain function and mutations in the gephyrin gene (GPHN) are associated with neurodevelopmental disorders and epilepsy. We identified bi-allelic variants in the GPHN gene, namely the missense mutation c.1264G > A and splice acceptor variant c.1315-2A > G, in a patient with developmental and epileptic encephalopathy. We demonstrate that the splice acceptor variant leads to nonsense-mediated mRNA decay. Furthermore, the missense variant (D422N) alters gephyrin structure, as examined by analytical size exclusion chromatography and circular dichroism-spectroscopy, thus leading to reduced receptor clustering and sensitivity towards calpain-mediated cleavage. In addition, both alterations contribute to an observed reduction of inhibitory signal transmission in neurons, which likely contributes to the pathological encephalopathy.

Copper and lead ion removal from wastewater using fava d'anta fodder (Dimorphandra gardneriana Tulasne).

The contamination of bodies of water by potentially hazardous elements has in recent decades become an environmental problem that poses serious risks to humans, fauna, flora and microbiota, compromising the quality of life of the present ecosystem. Therefore, effluents must be properly treated in a legally acceptable manner before their disposal in the environment. With this in mind, adsorption presents itself as an inexpensive efficient technique for the removal of potentially hazardous elements from effluents with excellent adsorption capacities when natural adsorbents are used. In this study, fava d'anta fodder was used in its crude and alkalinized form to remove Cu(II) and Pb(II) ions. Equilibrium studies were carried out using adsorption isotherms in batch systems with mono- and multi-elementary systems containing the two ions. The Langmuir and Freundlich models were applied to the isotherm studies, with the ions being better suited to the Langmuir model, with maximum adsorption capacities of 24.45 mg g-1 and 68.49 mg g-1 (crude form) and 11.12 mg g-1 and 35.34 mg g-1 (alkalinized form) in the mono-elementary system for Cu(II) and Pb(II) ions, respectively.

Neonatal mortality associated with sodium monofluoracetate in kids fed with colostrum from goats ingesting Amorimia septentrionalis / Mortalidade neonatal associada ao monofluoroacetato de sódio em cabritos alimentados com colostro de cabras ingerindo Amorimia septentrionalis

Sudden deaths after colostrum ingestion in kids and lambs born to mothers grazing in areas with Amorimia septentrionalis have been reported in the Brazilian northeastern semi-arid region, in Paraíba state. This study aimed to determine whether the sodium monofluoracetate (MF) contained in A. septentrionalis is eliminated in milk, causing the death of kids. After confirming gestation on the 25th day after mating, 26 goats were randomly distributed into three groups. In Group 1, eight goats received fresh leaves of A. septentrionalis in daily doses of 1g/kg body weight, administered at three different periods during gestation: from days 91 to 100, 116 to 125, and from day 140 until delivery day. In Group 2, consisting of 10 females, eight goats received 1g/kg body weight of A. septentrionalis dried and milled leaves, fed daily from the 140th day of gestation until delivery. The other two goats of this group did not ingest the plant during gestation and after delivery the colostrum supplied to their kids was replaced by colostrum of goats from that same group that had ingested the plant. Eight goats from Group 3 (control) did not ingest A. septentrionalis. Seven goats from Group 1 showed signs of poisoning from 2nd to 8th days of plant administration, in all periods, and recovered within 7 to 12 days. Another goat presented severe clinical signs and was submitted to euthanasia in extremis. Two goats aborted. Four kids, from two goats, received colostrum and, after 15 minutes, presented depression, breathing wheezing, lateral recumbence, bleating, and death. Two goats gave birth at night; the two kids were found dead and, at necropsy, it was verified that they were born alive. The last goat in this group gave birth to two kids which showed no signs of poisoning after colostrum ingestion. In Group 2, the eight goats that ingested dry leaves of the plant presented tachycardia and engorgement of the jugular veins; six aborted, and the kids of the other two goats died immediately after delivery without ingesting colostrum. The three kids of the two goats that did not ingest the plant during gestation did not show signs of poisoning after ingesting colostrum from the goats that had ingested the plant. In Group 3, all females kidded normally and the kids showed no signs of poisoning. Ten leaf samples of A. septentrionalis contained 0.00074% ±0.00018 MF. These results demonstrate that the MF of A. septentrionalis is eliminated in colostrum and may cause the death of kids. As in previous reports, the plant also caused abortion.(AU)

Mortes súbitas, após a ingestão do colostro, em cabritos e cordeiros nascidos de mães que pastejam em áreas com Amorimia septentrionalis são relatadas no semiárido da Paraíba. O objetivo deste trabalho foi determinar se o monofluoracetato de sódio (MF) contido em Amorimia septentrionalis é eliminado pelo leite, causando a morte dos cabritos. Após a confirmação da gestação no 25º dia após a cobertura, 26 cabras foram aleatoriamente distribuídas em três grupos. No Grupo 1, oito cabras receberam folhas frescas de A. septentrionalis em doses diárias de 1g/kg de peso vivo, administradas em três períodos diferentes durante a gestação: entre os dias 91 a 100, 116 a 125 e do 140º dia até o parto. No Grupo 2, composto por 10 fêmeas, oito cabras receberam 1g/kg de peso vivo de folhas secas e trituradas de A. septentrionalis, fornecida diariamente do 140º dia de gestação até o parto. As outras duas cabras desse grupo não ingeriram a planta durante a gestação e, ao parirem, o colostro fornecido aos seus cabritos foi substituído pelo colostro de cabras, desse mesmo grupo, que ingeriram a planta. Oito cabras do Grupo 3 (controle) não ingeriram A. septentrionalis. Sete cabras do Grupo 1 apresentaram sinais de intoxicação entre o 2º e 8º dia de administração da planta, em todos os períodos, e se recuperavam em 7 a 12 dias. Outra apresentou sinais clínicos graves e foi eutanasiada in extremis. Duas cabras abortaram. Quatro cabritos, oriundos de duas cabras, receberam colostro e, após 15 minutos, apresentaram depressão, respiração ofegante, decúbito lateral, berros e morte. Dois cabritos, nascidos de duas cabras que pariram durante a noite, foram encontrados mortos e os achados de necropsia permitem afirmar que nasceram vivos. A outra cabra desse grupo pariu dois cabritos que, mesmo mamando o colostro, não apresentaram sinais de intoxicação. No Grupo 2, as oito cabras que ingeriram a planta seca apresentaram taquicardia e ingurgitamento das veias jugulares; seis abortaram e os cabritos das outras duas morreram imediatamente após o parto, sem ingerir colostro. Os três filhotes das duas cabras que não ingeriram a planta durante a gestação não apresentaram sinais de intoxicação após ter ingerido colostro das cabras que tinham ingerido a planta. No Grupo 3, todas as fêmeas pariram normalmente e os filhotes não apresentaram sinais de intoxicação. Dez amostras de folhas de A. septentrionalis continham 0,00074% ± 0,00018 de MF. Estes resultados demonstram que o MF de A. septentrionalis, além de causar abortos, é eliminado pelo colostro podendo causar a morte dos cabritos.(AU)

Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: a prospective cohort study.

BACKGROUND: Molybdenum cofactor deficiency (MoCD) is characterised by early, rapidly progressive postnatal encephalopathy and intractable seizures, leading to severe disability and early death. Previous treatment attempts have been unsuccessful. After a pioneering single treatment we now report the outcome of the complete first cohort of patients receiving substitution treatment with cyclic pyranopterin monophosphate (cPMP), a biosynthetic precursor of the cofactor. METHODS: In this observational prospective cohort study, newborn babies with clinical and biochemical evidence of MoCD were admitted to a compassionate-use programme at the request of their treating physicians. Intravenous cPMP (80-320 µg/kg per day) was started in neonates diagnosed with MoCD (type A and type B) following a standardised protocol. We prospectively monitored safety and efficacy in all patients exposed to cPMP. FINDINGS: Between June 6, 2008, and Jan 9, 2013, intravenous cPMP was started in 16 neonates diagnosed with MoCD (11 type A and five type B) and continued in eight type A patients for up to 5 years. We observed no drug-related serious adverse events after more than 6000 doses. The disease biomarkers urinary S-sulphocysteine, xanthine, and urate returned to almost normal concentrations in all type A patients within 2 days, and remained normal for up to 5 years on continued cPMP substitution. Eight patients with type A disease rapidly improved under treatment and convulsions were either completely suppressed or substantially reduced. Three patients treated early remain seizure free and show near-normal long-term development. We detected no biochemical or clinical response in patients with type B disease. INTERPRETATION: cPMP substitution is the first effective therapy for patients with MoCD type A and has a favourable safety profile. Restoration of molybdenum cofactor-dependent enzyme activities results in a greatly improved neurodevelopmental outcome when started sufficiently early. The possibility of MoCD type A needs to be urgently explored in every encephalopathic neonate to avoid any delay in appropriate cPMP substitution, and to maximise treatment benefit. FUNDING: German Ministry of Education and Research; Orphatec/Colbourne Pharmaceuticals.

EVALUACIÓN DE ETILENGLICOL COMO CRIOPROTECTOR EN LA CRIOCONSERVACIÓN DE SEMEN DE BAGRE BLANCO (Sorubim cuspicaudus, PIMELODIDAE) / Evaluation of Ethylene Glycol as a Cryoprotectant in the Sperm Cryopreservation of Trans-Andean Shovelnose Catfish (Sorubim cuspicaudus, Pimelodidae)

Se evaluó el semen crioconservado de Sorubim cuspicaudus utilizando etilenglicol (ETG) a tres niveles de inclusión (5, 10, 15 %). Machos (n = 13) en fase de espermiación y hembras (n = 6) en maduración final se indujeron con 0,4 ml de Ovaprim®/Kg, después de 12 a 14 horas post-inducción se colectó el semen en viales Eppendorf de 2 ml de capacidad. Las diferentes soluciones crioprotectoras se prepararon con glucosa 6 % (p/v), leche en polvo descremada 5 % (pv) y agua destilada. El semen fue diluido en proporción 1:3 (semen:diluyente), empacado en macrotubos de 2,5 ml y congelado en vapores de nitrógeno líquido (NL) durante 30 minutos y luego almacenados en termos criogénicos sumergidos directamente en NL (- 196°C). El semen crioconservado fue descongelado en baño serológico a 35°C durante 90 segundos. La movilidad total, progresividad y velocidad espermática del semen fresco y descongelado se analizó con el software Sperm Class Analizer SCA® (Microptic SL, España). La fertilidad y eclosión se evaluó con 1,0-1,5 g de ovocitos en incubadoras experimentales de flujo ascendente de dos litros de capacidad. Se utilizó un diseño completamente aleatorizado. El semen fresco registró tasa de eclosión de 51,8°21 %, sin observarse diferencia significativa con la obtenida con el semen crioconservado con ETG 5 % (38,6 ° 13,9 %) (p> 0,05); mientras que ETG 15 % (9,6 ° 2,9 %) reportó la menor eclosión (p < 0,05). Los resultados sugieren que la solución crioprotectora compuesta por ETG 5 %, glucosa 6 % y leche en polvo 5 % es una alternativa viable para la crioconservación de semen de Sorubim cuspicaudus con fecundaciones similares al usar semen fresco.

The catfish Sorubim cuspicaudus cryopreservation semen was evaluated using three levels (5, 10, 15 %) of ethylene glycol (ETG). Males (n = 13) undergoing spermiation and in final maturation females (n = 6) were induced with 0.4 ml Ovaprim®/Kg, after 12 and 14 post-induction the semen was collected in 2 ml Eppendorf vials. The different cryoprotectants solutions were prepared with glucose 6 % (w/v) skimmed milk powder 5 % (w/v) and distilled water. The semen was diluted in ratio 1:3 (semen:extender), packed in macrotubes of 2.5 ml and frozen in liquid nitrogen (NL) vapor for 30 minutes, then the macrotubes were stored in cryogenic tanks submerged directly in NL (-196°C). The sperm were thawed in serological bath to 35°C for 90 seconds. The total motility, total progressivity and velocities in fresh and thawed semen were analyzed with the Sperm Class Analyzer software SCA® (Microptic SL, Spain). Fertility and hatching rates were assessed with 1.0-1.5 g of oocytes in experimental up flow incubators two liters, a completely randomized design was used. The hatching rate of fresh semen was 51,8°21 %, with no significant differences with semen cryopreserved with ETG 5 % (38.6 ° 13.9 %) (p> 0,05), while ETG 15 % (9.6 ° 2.9 %), recorded the lower hatching rate (p < 0.05). The results suggest that the cryoprotectant solution composed of ETG 5 %, glucose 6 % and powdered milk 5 % is a viable alternative for semen cryopreservation of the catfish Sorubim cuspicaudus.

Synthesis of cyclic pyranopterin monophosphate, a biosynthetic intermediate in the molybdenum cofactor pathway.

Cyclic pyranopterin monophosphate (1), isolated from bacterial culture, has previously been shown to be effective in restoring normal function of molybdenum enzymes in molybdenum cofactor (MoCo)-deficient mice and human patients. Described here is a synthesis of 1 hydrobromide (1·HBr) employing in the key step a Viscontini reaction between 2,5,6-triamino-3,4-dihydropyrimidin-4-one dihydrochloride and D-galactose phenylhydrazone to give the pyranopterin (5aS,6R,7R,8R,9aR)-2-amino-6,7-dihydroxy-8-(hydroxymethyl)-3H,4H,5H,5aH,6H,7H,8H,9aH,10H-pyrano[3,2-g]pteridin-4-one (10) and establishing all four stereocenters found in 1. Compound 10, characterized spectroscopically and by X-ray crystallography, was transformed through a selectively protected tri-tert-butoxycarbonylamino intermediate into a highly crystalline tetracyclic phosphate ester (15). The latter underwent a Swern oxidation and then deprotection to give 1·HBr. Synthesized 1·HBr had in vitro efficacy comparable to that of 1 of bacterial origin as demonstrated by its enzymatic conversion into mature MoCo and subsequent reconstitution of MoCo-free human sulfite oxidase-molybdenum domain yielding a fully active enzyme. The described synthesis has the potential for scale up.

[Usefullness of the Kramer's index in the diagnosis of hyperbilirubinemia of the newborn]. / Utilidad diagnóstica del método de Kramer para la detección clínica de la hiperbilirrubinemia neonatal.

The objective of the present study was to correlate seric values of bilirubin with the Kramer's index in a group of newborns with neonatal jaundice, from three different ethnic groups. This was a prospective, randomized, observational, descriptive-analytical, longitudinal, comparative and controlled study of 50 newborns with neonatal jaundice, without complications. They were divided into three groups: A (Control), n = 25, of Caucasian descent; B, n = 15, of local indigenous descent (Wayúu) and C, n = 10, of Afro-American descent. Each newborn was screened at the start of the study for their Kramer's dermic areas and simultaneously, a venous blood sample from the arm was taken for bilirubin quantification. They were compared through a correlation-regression analysis. Values at the beginning of the study were: serum bilirubin 12.02 +/- 3.41 mg/dL, and 62.8% of neonates were at Kramer's level 3. There were no differences among the ethnic groups studied and the correlation bilirubin/Kramer's index was r= 0.93 (p < 0.005). At the third day, both bilirubin and Kramer's indexes started to decrease. There were no ethnic differences. In conclusion, the Kramer's method offers multiple advantages to evaluate a jaundiced newborn; it is a safe, non-invasive method with no cost. Besides, it is of great help in the prevention of the kernicterus. It is recommended to implement the use of the Kramer method in all the newborns units in our Hospitals, preferably in those lacking transcutaneous bilirubinometers.

Utilidad diagnóstica del método de Kramer para la detección clínica de la hiperbilirrubinemia neonatal / Usefullness of the Kramer’s index in the diagnosis of hyperbilirubinemia of the newborn

El objetivo de la presente investigación fue correlacionar los valores séricos de bilirrubina con el índice de Kramer en un grupo de pacientes con ictericia neonatal de tres diferentes etnias. Representa un estudio prospectivo, aleatorio, observacional descriptivo-analìtico, longitudinal, comparativo y controlado en 50 recién nacidos con ictericia neonatal sin complicaciones. Se dividieron en 3 grupos: A (Control), n = 25 de origen caucásico; B, n = 15 de origen indígena local Wayúu y C, n = 10 de origen Afro americano. Al ingreso, a cada neonato se le determinaron las zonas dérmicas de Kramer y se le tomó una muestra de sangre venosa braquial para medir la bilirrubina de ingreso. Los valores al ingreso fueron: bilirrubina sérica 12,02 ± 3,41 mg/dL y el 62,8% estaban en nivel 3 de Kramer. No hubo diferencias entre los grupos étnicos estudiados y la correlación bilirrubina sérica-índice de Kramer fue de r= 0,93 (p < 0,005). Al 3er día se empezó a notar el descenso de la bilirrubina y de los índices de Kramer. El método de Kramer ofrece múltiples ventajas en la evolución del RN ictérico. No se encontraron diferencias raciales. Se recomienda implementar la aplicación de este método de Kramer en todas las unidades de neonatos en los hospitales, preferentemente en aquellas que carezcan de bilirrubinómetros transcutáneos.

The objective of the present study was to correlate seric values of bilirubin with the Kramer’s index in a group of newborns with neonatal jaundice, from three different ethnic groups. This was a prospective, randomized, observational, descriptive-analytical, longitudinal, comparative and controlled study of 50 newborns with neonatal jaundice, without complications. They were divided into three groups: A (Control), n = 25, of Caucasian descent; B, n = 15, of local indigenous descent (Wayúu) and C, n = 10, of Afro-American descent. Each newborn was screened at the start of the study for their Kramer’s dermic areas and simultaneously, a venous blood sample from the arm was taken for bilirubin quantification. They were compared through a correlation-regression analysis. Values at the beginning of the study were: serum bilirubin 12.02 ± 3.41 mg/dL, and 62.8% of neonates were at Kramer’s level 3. There were no differences among the ethnic groups studied and the correlation bilirubin/Kramer’s index was r= 0.93 (p < 0.005). At the third day, both bilirubin and Kramer’s indexes started to decrease. There were no ethnic differences. In conclusion, the Kramer’s method offers multiple advantages to evaluate a jaundiced newborn; it is a safe, non-invasive method with no cost. Besides, it is of great help in the prevention of the kernicterus. It is recommended to implement the use of the Kramer method in all the newborns units in our Hospitals, preferably in those lacking transcutaneous bilirubinometers.

Intoxicação experimental por Passiflora foetida (Passifloraceae) em caprinos / Experimental poisoning by Passiflora foetida (Passifloraceae) in goats

Passiflora foetida is mentioned as a toxic plant by farmers in northeastern Brazil. This research aimed to establish the toxicity of P. foetida for goats, in different seasons of the year, and to determine its toxic compound. Initially, the plant collected two days before administration was non toxic at the daily dose of 40g per kg of body weight (g/kg) given during two days. Furthermore, the plant was administered immediately after collection at a dose of 4-8g/kg to four goats. The animal that ingested 8g/kg showed severe clinical signs, but recovered after treatment with sodium thiosulfate. The other three goats showed mild signs of poisoning and recovered spontaneously. The plant was then administered during different seasons to 23 goats at the dose of 10g/kg. The plant was significantly (P<0.05) more toxic during the dry season than during the rainy season; 11 out of 14 goats that received the plant in the dry season showed clinical signs, but only 3 out of 13 goats that ingested the plant during the rainy season had signs. All goats with clinical signs recovered after the administration of sodium thiosulfate. Clinical signs were apathy, tachycardia and tachypnea, jugular venous pulse, incoordination, bellowing, mydriasis, and sternal recumbence followed by lateral recumbence. Before each administration the plant was tested for cyanide by the picric acid paper test to estimate the cyanide concentration in the plant, which was defined as slight, moderate, high, and very high. Samples with slight reaction were not toxic, those with moderate reaction induced mild signs of poisoning, and those with high reaction induced severe clinical signs. Samples with very high concentrations of cyanide were not observed. The results demonstrated that P. foetida is a cyanogenic plant, which causes poisoning after the ingestion of fresh leaves, mainly during the dry period.

Passiflora foetida é mencionada por produtores da região Nordeste como causa de intoxicação espontânea em animais. Este trabalho teve por objetivos avaliar a toxicidade de P. foetida em caprinos e determinar seu princípio ativo e a época do ano em que a mesma é tóxica. Inicialmente a planta administrada em duas doses diárias de 40g por kg de peso animal (g/kg) coletada dois dias antes da administração não resultou tóxica. Posteriormente a planta administrada imediatamente após a coleta resultou tóxica nas doses que variaram de 4 a 8 g/kg, em quatro caprinos. O animal que recebeu 8g/kg apresentou sinais clínicos graves e recuperou-se após a administração de tiossulfato de sódio. Os demais caprinos apresentaram sinais menos graves e se recuperaram espontaneamente. Posteriormente, a planta foi administrada em diferentes épocas a 23 caprinos na dose de 10g/kg. A planta foi significativamente mais tóxica (P<0,05) na época seca; no total, dos 14 caprinos que receberam a planta na época seca, 11 apresentaram sinais clínicos de intoxicação e dos 13 caprinos que receberam a planta na época das chuvas, apenas 3 apresentaram sinais clínicos. Todos os animais que apresentaram sinais clínicos, se recuperaram após a administração de tiosulfato de sódio. Os sinais clínicos caracterizavam-se por apatia, pulso venoso positi-vo, ataxia, berros, taquicardia e taquipneia, midríase e decúbito esternal seguido por decúbito lateral. Antes de cada administração era feito o teste do papel picrosódico para estimar o teor de cianeto na planta, classificando a reação em discreta, leve, moderada e acentuada. As amostras com reação discreta não apresentaram toxicidade, as com reação leve induziram sinais leves e as com reação moderada causaram sinais graves ou moderados de intoxicação. Não foram observados testes com reação acentuada. Os resultados do trabalho demonstram que P. foetida é uma planta cianogênica que causa intoxicação após a ingestão das folhas frescas[...]

Diarreia em caprinos associada ao consumo de arrabidaea corallina (Bignoniaceae) / Diarrhea in goats associated with the ingestion of arrabidaea corallina (Bignoniaceae)

Descreve-se um surto de intoxicação natural por Arrabidaea corallina (Jacq.) Sandw. (fam. Bignoniaceae) em caprinos no Município de Boqueirão, semiárido da Paraíba, durante a estação seca. De um rebanho de 550 caprinos maiores de um ano foram afetados 56 (10 por cento) e morreram 6 (1 por cento), com sinais clínicos de diarreia, aumento dos movimentos ruminais e depressão. Os demais animais se recuperaram após serem retirados da pastagem. O rebanho alimentava-se de pastagem nativa e nesse período dispunham de pouca forragem. Todavia, A. corallina era a única planta invasora que se mantinha verde e existia em grande quantidade. Um caprino afetado foi necropsiado. O intestino delgado apresentava conteúdo liquefeito, fétido e enegrecido e alterações de enterite catarral. Ao exame histológico observou-se enterite aguda, difusa e moderada, ocasionalmente com presença de Eimeria sp. Não foram observadas lesões macroscópicas ou microscópicas significativas em outros órgãos. A doença foi reproduzida experimentalmente em 4 caprinos após administração das folhas frescas de A. corallina em 3-6 doses diárias de 15g por kg de peso animal. Os caprinos apresentaram diarreia 3-4 dias após o início da ingestão e se recuperaram 5-6 dias após o final da administração. Conclui-se que o consumo de A. corallina é responsável pela ocorrência da doença em caprinos a campo. No entanto outras doenças como a infestação parasitária e a desnutrição podem contribuir para causar a morte dos animais. Recomenda-se a retirada de caprinos de áreas invadidas por A. corallina quando, em consequência de estiagem, não houver outra forragem disponível.

An outbreak of poisoning by Arrabidaea corallina (Jacq.) Sandw. (Fam. Bignoniaceae) in goats is reported, which occurred in the municipality of Boqueirão, semiarid of Paraíba, during the dry season. In a flock of 550 goats, older than one year of age, 56 (10 percent) were affected and 6 (1 percent) died. Clinical signs were diarrhea, increased ruminal movements and depression. The goats recovered after being moved to another paddock. The pasture had low forage availability and large amounts of A. corallina was the only other green plant observed. One goat was necropsied. The gut had liquid, fetid and blackish content, and showed catarrhal enteritis. Histology revealed acute, diffuse and moderate enteritis. Eimeria sp. was also observed. Non significant macroscopic or histological lesions were seen in other tissues. The disease was experimentally reproduced in four goats after the administration of fresh leaves of A. corallina, at 3-6 daily doses of 15g per kg of body weight. The animals showed diarrhea 3-4 days after the beginning of administration and recovered 5-6 days afterwards. It is concluded that the plant is responsible for the outbreak of diarrhea in goats, but parasitic disease or malnutrition can be contributing factors to the animal death. Goats should be withdrawn from paddocks with A. corallina if during the dry seasons no other forage is available.

Poisoning by Centratherum brachylepis in ruminants.

A disease causing anorexia and ruminal indigestion in cattle and goats, and also edema of the lips, tongue and face in goats, was associated with the ingestion of Centratherum brachylepis in pastures containing large amounts of the plant. On 3 farms with a total of 217 cattle and 140 goats, 57 (26%) cattle and 56 (40%) goats were affected, and 11 (5%) cattle and 34 (24%) goats died. In one cow that died there were widespread and severe histologic lesions in the rumen that consisted of vacuolation and ballooning degeneration of keratinocytes, and vesicle and pustule formation in the epithelium. C. brachylepis was administered orally to 3 sheep and 11 goats. Clinical signs similar to those observed in spontaneous field cases in goats were reproduced in 2 sheep and 3 goats that ingested 30-50 g/kg body weight of the plant when administered within 48 h of it being collected. C. brachylepis collected between 2 and 13 days prior to being administered caused no clinical signs in 1 sheep and 8 goats at dose rates of 30-300 g/kg body weight of the plant. These feeding studies provide evidence that C. brachylepis is the cause of the field disease observed and that the plant loses toxicity after harvesting.

[Nephroprotection from calcium channels blocking agents: a contribution to their probable mechanism of action]. / El efecto de nefroprotección de los calcio-antagonistas: una contribución al conocimiento de su probable mecanismo.

The prevalence and incidence of end-stage renal disease have progressively increased in the last 20 years and, both Hypertension (HT) and Diabetes Mellitus (DM) are the two most important causes of such a condition. Haemodynamic and metabolic perturbations contribute to the development and progression of renal disease and both HT and DM are key factors in the nephropathy. Blood pressure reduction alone is insufficient for maximal renal protection, hence the need for the knowledge of additional mechanisms for nephroprotection in order to establish preventive measures. To contribute to the knowledge of the nephroprotective mechanism of the calcium channel blocking agents (CB) of the dihydropiridine group, this prospective, experimental, longitudinal, and placebo-controlled clinical trial was performed in 55 non-diabetic normotensive and hypertensive adults receiving 3 CB drugs at antihypertensive doses and as monodoses. There were 3 groups. A: Normotensive (n = 25) receiving a single dose of Nitrendipine 20 mg; B: Type I and II hypertensive (n = 15) receiving Nifedipine for 12 weeks; and C: Type I and II hypertensive (n = 15) receiving Amlodipine 5 mg/day, for one week. Together with clinical and hemodynamic responses, biochemical parameters such as renal vasoactive hormones renin, prostaglandins and kallikreins, nitric oxide and cGMP were measured. The antihypertensive effect of CB drugs was confirmed and there was a significant increase in urinary kallikreins excretion related to an increase in nitric oxide. It is concluded that the nephroprotective effect of CB may be due to their capacity to increase urinary kallikreins which in turn, releases nitric oxide production. It is recommended to continue this research with larger number of hypertensive and diabetic patients with nephropathy and longer clinical trials.

Intoxicação experimental por Ipomoea asarifolia (Convolvulaceae) em caprinos e ovinos / Experimental poisoning by Ipomoea asarifolia (Convolvulaceae) in goats and sheep

Ipomoea asarifolia causa uma síndrome tremorgênica em ovinos, caprinos, bovinos e búfalos. Este experimento teve como objetivos determinar a toxicidade para caprinos de I. asarifolia verde, colhidas nas épocas de chuva e de estiagem, e da planta seca triturada, determinar a toxicidade da planta para ovinos, e determinar se o princípio ativo da planta é eliminado pelo leite em doses tóxicas para os cordeiros. No primeiro experimento a planta fresca colhida na época de estiagem e na época de chuvas foi administrada a 16 caprinos. A planta colhida na estiagem foi tóxica na dose diária de 5 e 10g por kg de peso animal (g/kg). A planta colhida na época de chuva foi tóxica na dose diária de 20 e 30g/kg, demonstrando que a planta é mais tóxica durante o período seco. A planta seca, colhida na época de estiagem foi administrada a 9 caprinos em doses diárias de 1.7, 2, 3.4 e 5.1g/kg. Doses de 3, 4 e 5.1g/kg causaram sinais clínicos, demonstrando que a planta mantém a toxicidade após a secagem. A planta fresca colhida na época de estiagem e na época de chuvas foi administrada a 10 ovinos. A planta colhida na estiagem foi tóxica na dose diária de 5g/kg e na época de chuva foi tóxica nas doses de 10 e 20g/kg. Estes resultados sugerem a maior susceptibilidade dos ovinos à intoxicação do que os caprinos. Como alguns produtores mencionam que cordeiros lactentes que não estão pastando se intoxicam através do leite, I. asarifolia foi administrada diariamente nas doses de 2.5, 5 e 10g/kg a 5 ovelhas, a partir do dia do parto (2 ovelhas), do último dia de prenhez (1 ovelha) e 60 dias antes da parição (2 ovelhas). As ovelhas, mas não os cordeiros, apresentaram sinais clínicos, sugerindo que o princípio ativo da planta não é eliminado no leite ou colostro em doses tóxicas para os cordeiros. Em um ovino eutanasiado não foram observadas lesões macroscópicas nem histológicas. Os achados ultra-estruturais mais significativos foram encontrados nos dendritos das...(AU)

Ipomoea asarifolia causes a tremogenic syndrome in sheep, goats, cattle and buffaloes. The objectives of the experiments were (1) to determine the toxicity to goats of fresh I. asarifolia collected during the raining and the dry season, and the toxicity of the dried plant, and (2) to determine the toxicity of the plant to sheep, and if the active principle is eliminated through the milk. In the first experiment the plant collected in the dry season and in the raining season was fed to 16 goats. The plant collected during the dry season caused clinical signs at the daily doses of 5g and 10g/kg body weight. The plant collected during the raining season was toxic at daily doses of 20g and 30g/kg, indicating that the plant is more toxic during the dry season. The plant collected in the dry season and dried was fed to 9 goats at doses of 1.7g, 2.0g, 3.4g, and 5.1g per kg. Daily doses of 3.0g, 4.0g and 5.1g/kg caused clinical signs, showing that the plant maintains its toxicity after being dried. In the second experiment the fresh plant collected in the dry and in the raining season was fed to 10 sheep. The plant collected in the dry season was toxic at the dose of 5g/kg, and the plant collected in the raining season was toxic at the doses of 10g and 20g/kg. The experimental results suggest that sheep are more susceptible to the poisoning than goats. As some farmers mentioned that suckling non-grazing lambs are poisoned by milk ingestion, I. asarifolia was fed at daily doses of 2.5g, 5.0g and 10g/kg for variable periods to 5 sheep from the day of parturition (2 sheep), after the last day of pregnancy (1 sheep) and 60 days before parturition (2 sheep). The sheep but not the lambs showed clinical signs of intoxication suggesting that the active principle is not eliminated through the milk at doses toxic for the lambs. In one euthanized sheep no gross or histologic lesions were detected. The main ultra-structural findings were found in Purkinje...(AU)

El efecto de nefroprotección de los calcio-antagonistas: una contribución al conocimiento de su probable mecanismo / Nephroprotection from calcium channels blocking agents: a contribution to their probable mechanism of action

La prevalencia e incidencia de la Insuficiencia Renal Crónica (IRC) han ido aumentando progresivamente en los últimos 20 años, y tanto la Hipertensión Arterial (HTA) como la Diabetes Mellitus (DM) son las dos causas más importantes de ambas situaciones. Los cambios hemodinámicos y metabólicos contribuyen en el desarrollo y progresión de la enfermedad renal en ambas HTA y DM, que son factores claves en la nefropatía. La reducción de la presión arterial sola no es suficiente para una máxima protección renal, de allí la necesidad del conocimiento de un mecanismo adicional para la nefroprotección para establecer medidas preventivas. A manera de contribuir al conocimiento de tal mecanismo nefroprotector de las drogas calcio-antagonistas (CA) del grupo dihidropiridinas se realizó este estudio prospectivo, experimental y longitudinal controlado con placebo en 55 adultos normotensos e hipertensos no-diabéticos que recibieron 3 drogas antihipertensivas CA a monodosis matutinas. Se dividieron en 3 grupos. Grupo A (n = 25): Control, normotensos, que recibieron dosis única de 20 mg de Nitrendipina (NIT). Grupo B (n = 15): Hipertensos tipos I y II que recibieron dosis de 20 mg de Nifedipina (NIF) por 12 semanas y Grupo C (n = 15): Hipertensos tipo I y II que recibieron monodosis de Amlodipina (AML) de 5 mg/d durante 1 semana. En conjunto con las respuestas clínica y hemodinámica, se analizaron parámetros bioquímicos como hormonas vasoactivas renales renina, prostaglandinas, calicreínas y óxido nítrico y también cGMP. El efecto antihipertensivo de los CA se confirmó, y hubo un aumento significativo de la excreción urinaria de calicreínas relacionado con el aumento del óxido nítrico.

Ectima contagioso em ovinos e caprinos no semi-árido da Paraíba / Contagious echtyma in sheep and goats in the semiarid of Paraíba, Brazil

Descrevem-se dez surtos de ectima contagioso em caprinos e dois em ovinos no semi-árido da Paraíba. Os animais jovens foram os mais afetados, mas em oito surtos animais adultos também foram afetados, principalmente cabras lactantes que apresentavam lesões no úbere. Em nenhum dos rebanhos afetados havia antecedentes de vacinação contra ectima contagioso. Histologicamente a epiderme apresentava acantose com hiperplasia pseudoepiteliomatosa e com múltiplos focos de degeneração hidrópica formando vesículas ou pústulas. Inclusões intracitoplasmáticas eosinofílicas foram observadas em queratinócitos. Havia restos celulares necróticos formando crostas, hiperqueratose e microabscessos intracorneais ou extensas áreas ulceradas. Na derme observou-se infiltrado inflamatório mononuclear difuso. Também foi registrado um caso humano em um pesquisador que tinha administrado planta por via oral a um caprino que, posteriormente, apresentou lesões de ectima contagioso. Neste caso, também foram observadas lesões características em uma biopsia e o vírus foi identificado por microscopia eletrônica. Conclui-se que a doença é endêmica no semi-árido e que é necessária a vacinação sistemática dos rebanhos para diminuir os prejuízos econômicos causados pela mesma. A utilização de luvas para o manuseio de animais afetados é necessária para evitar casos humanos da enfermidade.

Ten outbreaks of contagious ecthyma in goats and two in sheep in the semiarid of Paraíba State are reported. Young animals were more frequently affected, but in 8 outbreaks adult animals were also affected, mainly lactating goats which developed udder lesions. None of the affected flocks had been vaccinated. Upon histologic examination the epidermis showed acanthosis with pseudoepitheliomatous hyperplasia and multifocal ballooning degeneration forming vesicles or pustules. Eosinophilic inclusion bodies were observed in keratinocytes. Crust of necrotic cells, hyperkeratosis, and intracorneal microabscesses or large ulcerated areas were also observed. Severe diffuse infiltration by mononuclear cells was observed in the dermis. A human case was observed in an investigator that was feeding a goat that later appeared with lesions of the disease. In this case, the virus was identified by electron microscopy of a skin biopsy. These results show that contagious ecthyma is endemic in Northeastern Brazil and therefore systematic vaccination of the flocks is necessary to control the disease. The use of gloves to handle affected animals is advisable to minimize the risk of human exposure.

Intoxicação por Cnidoscolus phyllacanthus (Euphorbiaceae) em caprinos / Poisoning by Cnidoscolus phyllacanthus (Euphorbiaceae) in goats

Cnidoscolus phyllacanthus (Euphorbiaceae), com nome popular de favela, é uma planta normalmente espinhosa comum na caatinga. É considerada como forrageira e os animais, principalmente durante a seca, consomem as folhas que estão ao seu alcance ou as folhas secas caídas. A intoxicação espontânea por esta planta é relatada por fazendeiros no semi-árido quando animais têm acesso a plantas ou ramos recentemente cortados. Diferentes partes da planta moídas e secas, diluídas em água, são utilizadas por caçadores para matar pássaros. Para determinar a toxicidade de C. phyllacanthus, folhas verdes de plantas sem espinhos foram administradas a uma cabra em pequenas quantidades por via oral. Após o consumo de 4,7g por kg de peso do animal (g/kg) a cabra apresentou taquicardia, taquipneia, dispnéia, nistagmo, opistótono e decúbito esterno abdominal seguido de decúbito lateral. A morte ocorreu 30 minutos após o começo dos sinais. Folhas frescas de plantas sem espinho foram administradas a 8 caprinos em doses de 0,5-2,5g/kg sem que causassem sinais clínicos. Três animais apresentaram sinais clínicos após a ingestão de 3g/kg. Os sinais clínicos foram similares aos observados na intoxicação por ácido cianídrico e dois animais tratados com uma solução de tiossulfato de sódio a 20 por cento, na dose de 0,5ml/kg se recuperaram rapidamente em seguida ao tratamento. O terceiro recuperou-se espontaneamente. Folhas das mesmas plantas foram secadas ao sol durante períodos varáveis de 8-30 dias. O caprino que ingeriu a planta que tinha sido secada por 8 dias morreu após a ingestão de 3g/kg. O caprino que ingeriu a planta secada por 9 dias apresentou sinais clínicos após a ingestão de 1,13g/kg e se recuperou. Os caprinos que ingeriram a planta exposta ao sol por 10-29 dias apresentaram sinais clínicos após a ingestão de 3g/kg e se recuperaram espontaneamente ou mediante tratamento com tiossulfato de sódio. O caprino que ingeriu a planta que tinha sido exposta...

Cnidoscolus phyllacanthus (Euphorbiaceae), with the common name favela, is a generally spiny plant of the Brazilian semiarid. Mainly during the dry season livestock browse its leaves from the shrubs or ingest the dry leaves fallen to the ground. Farmers report the spontaneous poisoning by this plant when livestock has access to shrubs or branches that had been cut. Different parts of the ground fresh plant, diluted in water, are used by people in the semiarid to hunt birds. To determine the toxicity of C. phyllacanthus, leaves of the non-spiny plant were fed by hand to a goat by putting small amount into its mouth. After the consumption of 4.7g/kg body weight, the goat had tachycardia, tachypnoea, dyspnoea, nystagmus, opisthotonos and sternal recumbence. The death occurred 30 minutes after the onset of clinical signs. Fresh leaves from the same plants were given to 8 goats at doses of 0.5-2.5g/kg without causing clinical signs. Three goats showed clinical signs after the ingestion of 3g/kg. Clinical signs were similar to those observed in cyanide poisoning. Two goats given 0.5mg/kg of a 20 percent solution of sodium thiosulphate recovered immediately after treatment. Another goat recovered spontaneously. Leaves from the same plants were sun-dried during variable periods for 8-30 days, and then given to 8 goats. The goat that ingested the plant dried at the sun during 8 days died after the ingestion of 3 g/kg. The goat that ingested the plant, exposed to the sun for 9 days, showed clinical signs after the ingestion of 1.13g/kg, but recovered spontaneously. The goats that ingested the leaves exposed to the sun during 10-29 days showed clinical signs after the ingestion of 3g/kg, but recovered spontaneously or after treatment with sodium thiosulphate. No clinical signs were observed in the goat that ingested the plant that had been exposed to the sun during 30 days. In another experiment ground leaves of the plant were dried at the sun for...

Function of MoaB proteins in the biosynthesis of the molybdenum and tungsten cofactors.

Molybdenum (Mo) and tungsten (W) enzymes catalyze important redox reactions in the global carbon, nitrogen, and sulfur cycles. Except in nitrogenases both metals are exclusively associated with a unique metal-binding pterin (MPT) that is synthesized by a conserved multistep biosynthetic pathway, which ends with the insertion and thereby biological activation of the respective element. Although the biosynthesis of Mo cofactors has been intensively studied in various systems, the biogenesis of W-containing enzymes, mostly found in archaea, is poorly understood. Here, we describe the function of the Pyrococcus furiosus MoaB protein that is homologous to bacterial (such as MogA) and eukaryotic proteins (such as Cnx1) involved in the final steps of Mo cofactor synthesis. MoaB reconstituted the function of the homologous Escherichia coli MogA protein and catalyzes the adenylylation of MPT in a Mg2+ and ATP-dependent way. At room temperature reaction velocity was similar to that of the previously described plant Cnx1G domain, but it was increased up to 20-fold at 80 degrees C. Metal and nucleotide specificity for MPT adenylylation is well conserved between W and Mo cofactor synthesis. Thermostability of MoaB is believed to rely on its hexameric structure, whereas homologous mesophilic MogA-related proteins form trimers. Comparison of P. furiosus MoaB to E. coli MoaB and MogA revealed that only MogA is able to catalyze MPT adenylylation, whereas E. coli MoaB is inactive. In summary, MogA, Cnx1G, and MoaB proteins exhibit the same adenylyl transfer activity essential for metal insertion in W or Mo cofactor maturation.

Aspectos psíquicos en la evaluación de pacientes oncológicos

Se realiza investigación sobre prevalencia de trastornos ansiosos y depresivos mediante muestreo simple a pacientes (n=33) que acuden a consulta inicial o diagnóstico y de tratamiento inicial oncológico, aplicando el test de beck (depresión) y de Hamilton (ansiedad) durante un mes calendario. Se encuentra que 6.1 por ciento de la muestra reporta presencia de cuadro compatible con depresión grave, y 60,6 por ciento cuadro compatible con ansiedad mayor. A pesar de lo significativo de este hallazgo que recalca el importante grado de afectación de la esfera psíquica del paciente, no se observa correlación con interés en la detección, diagnóstico o manejo del problema psíquico, hay tendencia a la evaluación y tratamiento exclusivamente del problema del área física.

Lipoma submucoso del sigmoides con invaginación colorectal / Submucosal lipoma of the sigmoid with colorectal intussusception

Se presentan los hallazgos clínicos, radiológicos, endoscópicos, quirúrgicos y anatomopatológicos de una invaginación colorectal por lipoma submucoso del colon en una paciente de 40 años con síndrome disenteriforme y dolor abdominal; concomitantemente, obstrucción intestinal baja intermitente. Los estudios complementarios revelaron un tumor que ocupaba la luz intestinal y que se desplazaba; unas veces se palpaba en la fosa ilíaca izquierda, para luego desaparecer y encontrarse sólo accesible al tacto rectal. Endoscópicamente llamó la atención el aspecto "nacarado" de la superficie y la firmeza de la lesión. La persistencia de síntomas obstructivos condujo a la intervención quirúrgica encontrándose una invaginación colorectal actuando como cabeza de invaginación, un lipoma submucoso del sigmoides. Se encontró además un infarto segmentario de la pared intestinal. La paciente se recuperó bien y se encuentra libre de síntomas a los cinco meses del postoperatorio