RESUMEN
Morbid obesity and prolonged pregnancy are independently associated with adverse delivery and perinatal outcomes. We conducted a retrospective observational study on otherwise uncomplicated women with a body mass index (BMI) ≥ 40 kg/m2 where, having reached term, induction of labour (IOL) was planned, to prevent prolonged pregnancy. The primary aim was to describe delivery outcomes and short-term maternal and perinatal adverse events. Of 117 cases included, 69 (59%) laboured spontaneously before the induction date, while 48 (41%) required an IOL. Of 48 patients that underwent an IOL, 22 (45.8%) achieved vaginal delivery, compared to 55 (79.7%) who laboured spontaneously (p = <.001). Twenty-two (18.8%) of the 117 babies weighed more than 4000 g, with 13 of these delivered vaginally. Overall, term patients with morbid obesity who laboured spontaneously before requiring induction, had a high rate of vaginal delivery. However, when IOL was required, the rate of caesarean delivery rose dramatically.Impact statementWhat is already known on this subject? Morbid obesity and prolonged pregnancy are independently associated with adverse delivery and perinatal outcomes. Induction of labour (IOL) increases the workload in busy units.What do the results of this study add? These results help inform accurate counselling on delivery outcomes, which is integral to respectful care, for the continuously increasing numbers of morbidly obese pregnant women.What the implications are of these findings for clinical practice and/or further research? It is preferable to avoid semi- or urgent caesarean deliveries in morbidly obese women after IOL. The outcomes of earlier induction of labour from 39- or 40-weeks' gestation requires investigation. Earlier induction may reduce the numbers of caesarean deliveries for abnormal cardiotocograph during the process.
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Trabajo de Parto Inducido , Obesidad Mórbida , Embarazo Prolongado , Femenino , Humanos , Lactante , Embarazo , Parto Obstétrico/métodos , Trabajo de Parto Inducido/métodos , Resultado del Embarazo , Embarazo Prolongado/prevención & control , Estudios RetrospectivosRESUMEN
BACKGROUND: Obstetricians are cognisant of the serious nature of hypertensive disorders in pregnancy. Despite a 17% overall reduction in maternal deaths in South Africa between 2011 and 2016, there was a 14% increase in deaths due to hypertension. Delivery is the only known cure for pre-eclampsia, but the question regarding the safest route of delivery remains difficult to answer. OBJECTIVES: To determine the success rate of induction of labour (IoL) in patients with early-onset pre-eclampsia with severe features (EOPES) before 34 weeks' gestation. Furthermore, the data from the induction group were compared with those of the caesarean delivery (CD) groups where patients were not eligible for IoL. Additional objectives were to identify variables that could influence the success rate, to determine whether any delivery method was associated with increased morbidity, to assess the short-term maternal and neonatal outcomes, and to make recommendations for future decision-making regarding delivery for women with EOPES. METHODS: In this single-institution retrospective observational study, all cases in which a decision for delivery was made before 34 weeks 0 days of gestation (or the infant's birthweight was ≤2 000 g with uncertain gestation) at Tygerberg Hospital, Cape Town, between 1 January and 30 June 2017 were identified from the electronic birth register. The cohort fitting the inclusion criteria was subdivided into IoL and CD groups. RESULTS: From a total of 3 938 deliveries, 168 patients met the inclusion criteria. IoL was indicated in 55 cases, resulting in 20 vaginal deliveries (VDs) (36%) and 35 CDs (64%). The remaining 113 patients were not candidates for IoL; of these, 89 required emergency CDs and 24 had semi-elective CDs. In the IoL group with abnormal umbilical artery Dopplers (UADs) there was 1 VD, and 4 CDs were performed for fetal compromise. Of cases with an estimated fetal weight (EFW) ≤3rd centile, emergency CD was required in 24 (65%), and 8 (22%) were considered for IoL, in 6 of which CD was required. CONCLUSIONS: Of the EOPES population, 36% had successful IoL that culminated in VD. VD was more likely to occur with fetal growth appropriate for gestational age. The likelihood of CD increased if the UAD was abnormal, if the EFW was ≤3rd centile or if eclampsia was present. The decision to induce should be considered carefully in these circumstances.
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Cesárea/estadística & datos numéricos , Parto Obstétrico/estadística & datos numéricos , Preeclampsia/fisiopatología , Resultado del Embarazo , Adulto , Peso al Nacer , Femenino , Edad Gestacional , Humanos , Recién Nacido , Trabajo de Parto Inducido/estadística & datos numéricos , Embarazo , Estudios Retrospectivos , Sudáfrica , Arterias Umbilicales/diagnóstico por imagenRESUMEN
Recent studies have shown that the detection of SARS-CoV-2 genetic material in wastewater may provide the basis for a surveillance system to track the environmental dissemination of this virus in communities. An effective wastewater-based epidemiology (WBE) system may prove critical in South Africa (SA), where health systems infrastructure, testing capacity, personal protective equipment and human resource capacity are constrained. In this proof-of-concept study, we investigated the potential of SARS-CoV-2 RNA surveillance in untreated wastewater as the basis for a system to monitor COVID-19 prevalence in the population, an early warning system for increased transmission, and a monitoring system to assess the effectiveness of interventions. The laboratory confirmed the presence (qualitative analysis) and determined the RNA copy number of SARS-CoV-2 viral RNA by reverse transcription polymerase chain reaction (quantitative) analysis from 24-hour composite samples collected on 18 June 2020 from five wastewater treatment plants in Western Cape Province, SA. The study has shown that a WBE system for monitoring the status and trends of COVID-19 mass infection in SA is viable, and its development and implementation may facilitate the rapid identification of hotspots for evidence-informed interventions.
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ARN Viral/aislamiento & purificación , SARS-CoV-2/aislamiento & purificación , Aguas Residuales/virología , COVID-19/epidemiología , Monitoreo del Ambiente , Monitoreo Epidemiológico , Humanos , Neumonía Viral/epidemiología , Prueba de Estudio Conceptual , Sudáfrica/epidemiologíaRESUMEN
Metformin is the first line therapy of type 2 diabetics, but continued reduction of their life expectancy warrants further investigation into alternative treatment strategies. This study reports on the combinational use of metformin with aspalathin, a C-glucosyl dihydrochalcone with known glucose lowering and antioxidant properties, as an effective hypoglycemic therapy in a type 2 diabetic (db/db) mouse model. When tested as a monotherapy, a low dose of aspalathin (13 mg/kg) showed no effect, while a high dose (130 mg/kg) has already displayed a better potential than metformin in protecting against diabetes associated symptoms in db/db mice. Thus, it remains of interest to determine whether this dihydrochalcone can improve the efficacy of metformin. The results showed that this combination therapy was more effective than the use of metformin as a monotherapy in ameliorating diabetes associated symptoms, including abnormal raised fasting plasma glucose levels, impaired glucose tolerance, as well as excessively increased body weights and fat content. The treated mice also had reduced food and water consumption when compared to untreated controls, with a pronounced effect evident in the last week of treatment. Therefore, this study supports further investigations into the ameliorative effect of combination therapy of metformin and aspalathin against diabetes associated symptoms.
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Aspalathus , Chalconas/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Animales , Chalconas/aislamiento & purificación , Diabetes Mellitus Tipo 2/sangre , Sinergismo Farmacológico , Flavonoides/administración & dosificación , Flavonoides/aislamiento & purificación , Hipoglucemiantes/aislamiento & purificación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
Doxorubicin is a highly effective, first line chemotherapeutic agent used in the management of hematological and solid tumors. The effective use of doxorubicin in cancer therapy has been severely limited owing to its well-documented cardiotoxic side effect. Oxidative stress, lipid peroxidation, apoptosis as well as dysregulation of autophagy, has been implicated as a major contributor associated with doxorubicin-induced cardiotoxicity. Increased oxidative stress and lipid peroxidation are known to enhance the production of reactive oxygen species, while autophagy has been reported to protect the cell from stress stimuli or, alternatively, contribute to cell death. Nonetheless, to date, no single chemical synthesized drug is available to prevent the harmful action of doxorubicin without reducing its anti-cancer efficacy. Therefore, the search for an effective and safe antagonist of doxorubicin-induced cardiotoxicity remains a challenge. In recent years, there has been much interest in the role plant-derived polyphenols play in the regulation of oxidative stress and autophagy. Therefore, the present review renders a concise overview of the mechanism associated with doxorubicin-induced cardiotoxicity as well as giving insight into the role plant-derived phytochemical play as a possible adjunctive therapy against the development of doxorubicin-induced cardiotoxicity.
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Cardiotoxicidad/prevención & control , Doxorrubicina/efectos adversos , Polifenoles/farmacología , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Cardiotoxicidad/etiología , Doxorrubicina/administración & dosificación , Humanos , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
About 40% of the dorsal raphe nucleus (DRN) neurons co-express serotonin (5-HT) and galanin. Serotonergic pathways from the DRN to the amygdala facilitate learned anxiety, while those from the DRN to the dorsal periaqueductal grey matter (DPAG) impair innate anxiety. Previously, we showed that galanin infusion in the DRN of rats induces anxiolytic effect by impairing inhibitory avoidance without changing escape behaviour in the elevated T-maze (ETM). Here, we evaluated: (1) which galanin receptors would be involved in the anxiolytic effect of galanin in the DRN of rats tested in the ETM; (2) the effects of galanin intra-DRN on panic-like behaviours evoked by electrical stimulation of the DPAG. The activation of DRN GAL1 receptors by M617 (1.0 and 3.0nmol) facilitated inhibitory avoidance, whereas the activation of GAL2 receptors by AR-M1896 (3.0nmol) impaired the inhibitory avoidance in the ETM, suggesting an anxiogenic and an anxiolytic-like effect respectively. Both agonists did not change escape behaviour in the ETM or locomotor activity in the open field. The anxiolytic effect of AR-M1896 was attenuated by the prior administration of WAY100635 (0.18nmol), a 5-HT1A antagonist. Galanin (0.3nmol) administered in the DRN increased discreetly flight behaviours induced by electrical stimulation of the DPAG, suggesting a panicolytic effect. Together, our results showed that galanin mediates opposite anxiety responses in the DRN by activation of GAL1 and GAL2 receptors. The anxiolytic effect induced by activation of Gal2 receptors may depend on serotonergic tone. Finally, the role of galanin in panic related behaviours remains uncertain.
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Ansiedad/tratamiento farmacológico , Núcleo Dorsal del Rafe/efectos de los fármacos , Galanina/farmacología , Receptor de Galanina Tipo 1/efectos de los fármacos , Receptor de Galanina Tipo 2/efectos de los fármacos , Animales , Ansiolíticos/farmacología , Ansiedad/metabolismo , Trastornos de Ansiedad/tratamiento farmacológico , Núcleo Dorsal del Rafe/metabolismo , Galanina/metabolismo , Masculino , Sustancia Gris Periacueductal/efectos de los fármacos , Ratas Wistar , Receptor de Galanina Tipo 1/metabolismo , Receptor de Galanina Tipo 2/metabolismo , Antagonistas del Receptor de Serotonina 5-HT1/farmacologíaRESUMEN
Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle that contributes to cardiovascular deaths in the diabetic population. Excessive generation of free radicals has been directly implicated in the pathogenesis of DCM. The use of antioxidants, through dietary supplementation, to combat increased cellular oxidative stress has gained popularity worldwide. Aspalathus linearis (rooibos) is a popular herbal tea that contains a novel antioxidant, aspalathin. Literature has reported on the antidiabetic, anti-inflammatory and free radical scavenging effects of rooibos. However, its protective effect against DCM has not been established. Therefore, this study investigated whether chronic exposure to an aqueous extract of fermented rooibos (FRE) has an ex vivo cardioprotective effect on hearts obtained from streptozotocin (STZ) induced diabetic rats. Adult Wistar rats were injected with 40 mg/kg of STZ. Two weeks after STZ injection, cardiomyocytes were isolated and cultured. Cultured cardiomyocytes were treated with FRE (1 and 10 µg/ml), vitamin E (50 µg/ml), and n-acetyl cysteine (1mM) for 6h, before exposure to either hydrogen peroxide (H2O2) or an ischemic solution. Cardiomyocytes exposed to H2O2 or an ischemic solution showed a decrease in metabolic activity and glutathione content with a concomitant increase in apoptosis and intracellular reactive oxygen species. Pretreatment with FRE was able to combat these effects and the observed amelioration was better than the known antioxidant vitamin E. This study provides evidence that an aqueous extract of fermented rooibos protects cardiomyocytes, derived from diabetic rats, against experimentally induced oxidative stress and ischemia.
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Aspalathus , Cardiomiopatías Diabéticas/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Evaluación Preclínica de Medicamentos , Fermentación , Glutatión/metabolismo , Masculino , Isquemia Miocárdica/tratamiento farmacológico , Miocitos Cardíacos/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/análisisRESUMEN
Increased levels of free fatty acids (FFAs), specifically saturated free fatty acids such as palmitate are associated with insulin resistance of muscle, fat and liver. Skeletal muscle, responsible for up to 80% of the glucose disposal from the peripheral circulation, is particularly vulnerable to increased levels of saturated FFAs. Rooibos (Aspalathus linearis) and its unique dihydrochalcone C-glucoside, aspalathin, shown to reduce hyperglycemia in diabetic rats, could play a role in preventing or ameliorating the development of insulin resistance. This study aims to establish whether rooibos can ameliorate experimentally-induced insulin-resistance in C2C12 skeletal muscle cells. Palmitate-induced insulin resistant C2C12 cells were treated with an aspalathin-enriched green (unfermented) rooibos extract (GRE), previously shown for its blood glucose lowering effect in vitro and in vivo or an aqueous extract of fermented rooibos (FRE). Glucose uptake and mitochondrial activity were measured using 2-deoxy-[³H]-D-glucose, MTT and ATP assays, respectively. Expression of proteins relevant to glucose metabolism was analysed by Western blot. GRE contained higher levels of all compounds, except the enolic phenylpyruvic acid-2-O-glucoside and luteolin-7-O-glucoside. Both rooibos extracts increased glucose uptake, mitochondrial activity and ATP production. Compared to FRE, GRE was more effective at increasing glucose uptake and ATP production. At a mechanistic level both extracts down-regulated PKC θ activation, which is associated with palmitate-induced insulin resistance. Furthermore, the extracts increased activation of key regulatory proteins (AKT and AMPK) involved in insulin-dependent and non-insulin regulated signalling pathways. Protein levels of the glucose transporter (GLUT4) involved in glucose transport via these two pathways were also increased. This in vitro study therefore confirms that rooibos can ameliorate palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Inhibition of PKC θ activation and increased activation of AMPK and AKT offer a plausible mechanistic explanation for this ameliorative effect.
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Aspalathus , Resistencia a la Insulina/fisiología , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Ácido Palmítico/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Aspalathus/química , Línea Celular , Hiperinsulinismo/inducido químicamente , Hiperinsulinismo/tratamiento farmacológico , Ratones , Músculo Esquelético/enzimología , Ácido Palmítico/farmacología , Extractos Vegetales/farmacologíaRESUMEN
Rooibos, an endemic South African plant, known for its use as herbal tea, has potential as an antidiabetic herbal product, following recent demonstration of the glucose lowering effect of its major flavonoid, the dihydrochalcone C-glucoside aspalathin. The purpose of this study was to confirm antidiabetic activity for rooibos extract high in aspalathin content. An extract (SB1) was selected after screening for high aspalathin content and α-glucosidase inhibition activity. On-line HPLC-biochemical detection confirmed α-glucosidase inhibitory activity for aspalathin. In vitro the extract induced a dose response increase in glucose uptake (5 × 10â»5 to 5 µg/ml) on C2C12 myotubules. Aspalathin was effective at 1, 10 and 100 µM, while rutin was effective at 100 µM. In the Chang cells only the extract was effective. In vivo the extract sustained a glucose lowering effect comparable to metformin over a 6h period after administration (25mg/kg body weight (BW)) to STZ-induced diabetic rats. In an oral glucose tolerance test the extract (30 mg/kg BW) was more effective than vildagliptin (10mg/kg BW), a dipeptidyl peptidase-4 inhibitor. An aspalathin-rutin mixture (1:1; m/m) dosed at 1.4 mg/kg BW, but not the single compounds separately, reduced blood glucose concentrations of STZ-induced diabetic rats over a 6h monitoring period. The improved hypoglycemic activity of the aspalathin-rutin mixture and the extract illustrated synergistic interactions of polyphenols in complex mixtures.
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Aspalathus/química , Glucemia/metabolismo , Chalconas/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Adamantano/análogos & derivados , Adamantano/farmacología , Animales , Línea Celular , Chalconas/farmacología , Diabetes Mellitus Experimental/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Prueba de Tolerancia a la Glucosa , Inhibidores de Glicósido Hidrolasas , Hipoglucemiantes/farmacología , Masculino , Nitrilos/farmacología , Extractos Vegetales/farmacología , Pirrolidinas/farmacología , Ratas , Ratas Wistar , Rutina/farmacología , Rutina/uso terapéutico , VildagliptinaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Communities in Chilumba, Malawi use herbal tea prepared from Fadogia ancylantha Schweinf (Rubiaceae) leaves for the management of diabetes, hypertension and alleviation of symptoms of gastrointestinal disorders and pneumonia. The objective of the study was to evaluate the in vitro antidiabetic, anti-oxidant and antimicrobial activities of the crude extracts of the leaves prepared by using three different extraction methods. MATERIALS AND METHODS: Each of the organic, cold and hot aqueous extracts of the herbal tea was evaluated for its effect on glucose uptake in C2C12 muscle and Chang cell lines. Metformin and insulin were used as positive controls. The anti-oxidant activity, based on neutralisation of DPPH free radicals, was determined spectrophotometrically. The Agar serial dilution method was utilised to determine the minimum inhibitory concentration (MIC) of the extracts for the selected fungal and bacterial strains. RESULTS AND DISCUSSION: The organic extract (12.5µg/ml) exhibited the highest in vitro glucose uptake increases in Chang cells (181.24±0.29%) and C2C12 muscle cells (172.29±0.32%) while the hot and cold aqueous extracts gave lower uptakes, 145.94±0.37% and 138.70±0.52% in Chang cells respectively. At 100µg/ml, aqueous extracts gave significantly higher (p<0.01) anti-oxidant activity (range 85.78-86.29%) than their organic counterpart (68.16%). The minimum inhibitory concentration (156µg/ml) was obtained in the organic extract against the fungus Aspergillus fumigatus and moderate growth inhibition was observed with other test micro-organisms. The hot aqueous extract inhibited the growth of all test organisms except Pseudomonas aeruginosa. The cold aqueous extract was inactive against Pseudomonas aeruginosa and Candida albicans. The differences in the MIC values between the aqueous extracts seem to suggest that raised temperatures, as traditionally practised, facilitate the extraction of secondary bioactive metabolites. CONCLUSION: These results show that Fadogia ancylantha extracts have high antidiabetic and anti-oxidant properties.
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Antibacterianos/farmacología , Antifúngicos/farmacología , Antioxidantes/farmacología , Glucosa/metabolismo , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Rubiaceae , Aspergillus/efectos de los fármacos , Aspergillus/crecimiento & desarrollo , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Línea Celular , Malaui , Pruebas de Sensibilidad Microbiana , Pseudomonas/efectos de los fármacos , Pseudomonas/crecimiento & desarrolloRESUMEN
Athrixia phylicoides DC. is an aromatic shrub indigenous to the eastern parts of Southern Africa. Indigenous communities brew "bush tea" from dried twigs and leaves of A. phylicoides, which is consumed as a beverage and used for its medicinal properties. Plant polyphenols have been shown to be beneficial to Type 2 diabetes mellitus (T2D) and obesity. Aqueous extracts of the plant have been shown to be rich in polyphenols, in particular phenolic acids, which may enhance glucose uptake and metabolism. The aim of this study was to determine the phenolic composition of a hot water A. phylicoides extract and assess its in vitro effect on cellular glucose utilisation. The most abundant phenolic compounds in the extract were 6-hydroxyluteolin-7-O-glucoside, chlorogenic acid, protocatechuic acid, a di-caffeoylquinic acid and a methoxy-flavonol derivative. The extract increased glucose uptake in C2C12, Chang and 3T3-L1 cells, respectively. Intracellular glucose was utilised by both oxidation (C2C12 myocytes and Chang cells; p < 0.01 and p < 0.05, respectively) and by increased glycogen storage (Chang cells; p < 0.05). No cytotoxicity was observed in Chang cells at the concentrations tested. The effects of the extract were not dose-dependent. A. phylicoides aqueous extract stimulated in vitro glucose uptake and metabolism, suggesting that consumption of this phenolic-rich extract could potentially ameliorate metabolic disorders related to obesity and T2D.
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Asteraceae/química , Glucosa/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células 3T3-L1/efectos de los fármacos , África Austral , Animales , Ácido Clorogénico/análisis , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Glucosa/farmacocinética , Glucógeno/metabolismo , Hidroxibenzoatos/análisis , Luteolina/análisis , Ratones , Fenoles/análisis , Fenoles/química , Plantas Medicinales/química , Ácido Quínico/análogos & derivadosRESUMEN
The Indo-Pacific is a very complex region encompassing several micro-continents with unique tectonic and geomorphologic histories. Unsurprisingly, the biogeographic history of Indo-Pacific biota is generally poorly known, especially that of organisms found in the heart of the region, the biodiversity hotspot known as Wallacea. Here, we explore the biogeographic history of the Indo-Pacific butterfly genus Cethosia using all known species and many distinctive subspecies. Cethosia butterflies span the Indo-Pacific tropics, including several lineages with localized endemism that are critically important when reconstructing biogeographic history of the Indo-Pacific and, in particular, of Wallacea. A phylogenetic hypothesis is proposed, based on sequences of the mitochondrial genes cytochrome oxidase subunit I (COI) and NADH dehydrogenase 5 (ND5), and the nuclear wingless gene. Both Maximum Parsimony and Bayesian analyses showed that the genus is monophyletic and consistently recovered seven, generally very well supported, clades, namely the cydippe, leschenault, biblis, nietneri, hypsea, penthesilea and cyane clades. Species group relationships are largely concordant with general morphology (i.e., wing pattern and colouration) and, based on the phylogeny, we propose a revised systematic classification at the species level. The evolution of the genus appears associated with the inferred geological history of the region, in particular with respect to the expanding Wallacea theory, whereby ancient connected terranes were fragmented during the mid Miocene to early Pliocene, approximately 14-3 Mya. Recent diversification events in Cethosia were likely promoted by climatic fluctuations during the Pliocene and, to a lesser extent, the Pleistocene. Our results support the view that, while dispersal has been important for Cethosia throughout much of the region, the high levels of island endemism and the essentially allopatric radiations recovered in Cethosia in Wallacea are better explained by vicariant processes linked to the history of formation of micro-continent and associated palaeo islands.
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Mariposas Diurnas/genética , Evolución Molecular , Especiación Genética , Filogenia , Animales , Biodiversidad , Mariposas Diurnas/clasificación , Núcleo Celular/genética , ADN Mitocondrial/genética , Geografía , Islas del Pacífico , Análisis de Secuencia de ADNRESUMEN
In rodents, the cholinomimetic convulsant pilocarpine is widely used to induce status epilepticus (SE), followed by hippocampal damage and spontaneous recurrent seizures, resembling temporal lobe epilepsy. This model has initially been described in rats, but is increasingly used in mice, including the C57BL/6 (B6) inbred strain. In the present study, we compared the effects of pilocarpine in three B6 substrains (B6JOla, B6NHsd and B6NCrl) that were previously reported to differ in several behavioral and genetic aspects. In B6JOla and B6NHsd, only a small percentage of mice developed SE independently of whether pilocarpine was administered at high bolus doses or with a ramping up dosing protocol, but mortality was high. The reverse was true in B6NCrl, in which a high percentage of mice developed SE, but mortality was much lower compared to the other substrains. However, in subsequent experiments with B6NCrl mice, striking differences in SE induction and mortality were found in sublines of this substrain coming from different barrier rooms of the same vendor. In B6NCrl from Barrier #8, administration of pilocarpine resulted in a high percentage of mice developing SE, but mortality was low, whereas the opposite was found in B6NCrl mice from four other barriers of the same vendor. The analysis of F1 mice from a cross of female Barrier 8 pilocarpine-susceptible mice with resistant male mice from another barrier (#9) revealed that F1 male mice were significantly more sensitive to pilocarpine than the resistant parental male mice whereas female F1 mice were not significantly different from resistant Barrier 9 females. These observations strongly indicate X-chromosome linked genetic variation as the cause of the observed phenotypic alterations. To our knowledge, this is the first report which demonstrates that not only the specific B6 substrain but also sublines derived from the same substrain may markedly differ in their response to convulsants such as pilocarpine. As the described differences have a genetic basis, they offer a unique opportunity to identify the genes and pathways involved and contribute to a better understanding of the underlying molecular mechanisms of seizure susceptibility.
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Convulsivantes/toxicidad , Epilepsia/inducido químicamente , Epilepsia/genética , Predisposición Genética a la Enfermedad/genética , Pilocarpina/toxicidad , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Resistencia a Medicamentos/genética , Epilepsia/mortalidad , Femenino , Variación Genética/genética , Genotipo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Mortalidad , Fenotipo , Caracteres Sexuales , Especificidad de la Especie , Cromosoma X/genéticaRESUMEN
In the present study the binding of strontium with pure calcium silicate hydrates (C-S-H) has been investigated using batch-type experiments. Synthetic C-S-H phases with varying CaO:SiO(2) (C:S) mol ratios, relevant to non-degraded and degraded hardened cement paste, were prepared in the absence of alkalis (Na(I), K(I)) and in an alkali-rich artificial cement pore water (ACW). Two types of experimental approaches have been employed, investigating sorption and co-precipitation processes, respectively. The Sr(II) sorption kinetics were determined as well as sorption isotherms, the effect of the solid to liquid ratio and the composition (C:S ratio) of the C-S-H phases. In addition, the reversibility of the Sr(II) sorption was tested. It was shown that both the sorption and co-precipitation tests resulted in Sr(II) distribution ratios which were similar in value, indicating that the same sites are involved in Sr(II) binding. In alkali-free solutions, the Sr(II) uptake by C-S-H phases was described in terms of a Sr(2+)-Ca(2+) ion exchange model. The selectivity coefficient for the Sr(2+)-Ca(2+) exchange was determined to be 1.2+/-0.3.
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Compuestos de Calcio/química , Restauración y Remediación Ambiental/métodos , Silicatos/química , Radioisótopos de Estroncio/aislamiento & purificación , Estroncio/aislamiento & purificación , Contaminantes Radiactivos/química , Contaminantes Radiactivos/aislamiento & purificación , Estroncio/química , Radioisótopos de Estroncio/químicaRESUMEN
Early exposure to adverse experiences may lead to specific changes in hippocampal glucocorticoid function resulting in abnormalities within the hypothalamic-adrenal axis. Given interactions between the neuroendocrine and central serotonergic systems, we hypothesized that exposure to early trauma would lead to abnormal hypothalamic-adrenal axis activity that would be normalized by pretreatment with a selective serotonin re-uptake inhibitor. Hypothalamic-adrenal axis function was assessed by determining basal corticosterone levels and hippocampal glucocorticoid receptor immunoreactivity. Rats were subjected to a triple stressor on postnatal day 28, and again to a single swim re-stress session on postnatal day 35 and postnatal day 60. On postnatal day 61 i.e. 24 h after the last re-stress, trunk blood was collected for serum corticosterone determinations and hippocampal tissue was collected for immunohistochemistry of glucocorticoid receptors. Escitalopram (5mg/kg) or saline vehicle was administered from postnatal day 47-postnatal day 60 via osmotic mini-pumps. Animals exposed to early life trauma showed an increase in basal corticosterone levels, and a significant decrease in the ratio of glucocorticoid receptor positive cells to total cells in the hilus, granule cell layer and the dentate gyrus. Both the increase in basal corticosterone and decrease in glucocorticoid receptor immunoreactivity were reversed by escitalopram pretreatment. These data confirm alterations in hypothalamic-adrenalaxis function that may stem from decreases in glucocorticoid receptor levels, in response to early adverse experiences, and demonstrate that these alterations are reversed by serotonin re-uptake inhibitor pretreatment.
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Envejecimiento/fisiología , Citalopram/farmacología , Giro Dentado/crecimiento & desarrollo , Giro Dentado/metabolismo , Regulación hacia Abajo/fisiología , Receptores de Glucocorticoides/metabolismo , Estrés Psicológico/metabolismo , Animales , Giro Dentado/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Glucocorticoides/sangre , Glucocorticoides/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiopatología , Ratas , Ratas Sprague-Dawley , Receptores de Glucocorticoides/efectos de los fármacos , Serotonina/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/fisiopatología , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/fisiopatologíaRESUMEN
The morphology of the anterior and posterior internal vertebral venous plexus (IVVP) in human fetuses between 21-25 weeks of gestational age is described. The results are compared to the findings of a previous morphological study of the IVVP in the aged. The morphological pattern of the anterior IVVP in the fetus is very similar with the anterior IVVP in the aged human. In contrast, the posterior IVVP in the fetus lacks the prominent transverse bridging veins that are present in the aged lower thoracic and the lumbar posterior IVVP. The background of these morphological differences is unclear. Maybe the thoracolumbar part of the posterior IVVP is subject to "developmental delay," or the observed differences in the aged may result from functional and age-related factors that trigger this part of the vertebral venous system during (erect) life. The observed age related morphological differences of the posterior IVVP support the concept of the venous origin of the spontaneous spinal epidural hematoma (SSEH).
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Desarrollo Fetal , Feto/irrigación sanguínea , Hematoma Espinal Epidural , Columna Vertebral/irrigación sanguínea , Venas/embriología , Adulto , Anciano , Anciano de 80 o más Años , Cadáver , Femenino , Edad Gestacional , Hematoma Espinal Epidural/etiología , Hematoma Espinal Epidural/patología , Humanos , Masculino , Persona de Mediana Edad , Columna Vertebral/embriología , TóraxRESUMEN
The primary objective of this cadaveric study was to review the morphological variations of the anatomy of the human carotid artery bifurcation relevant to carotid endarterectomy (CEA) and carotid artery stent-supported angioplasty (CSSA). We quantify carotid bifurcation plaque morphology. Results showed that the angle of deviation at the origin of the internal carotid artery (ICA), in relation to the common carotid artery (CCA), measured a mean of 21.8 degrees with a range from seven to 45 degrees. This anatomical finding is important for the interventionalist concerned with insertion of a carotid stent. The angle of the ICA origin may be an independent risk factor for early atherosclerotic changes at the ICA bulb. Carotid bifurcation plaque was observed in a small, random cohort of seven out of 13 cadavers, and contributed to a mean stenosis of 15.2% (range 5.0-34.8%). Plaque morphology (n = 7) showed haemorrhage (29%), superficial thrombosis (57%), calcification (71%), areas of focal necrosis (71%), neovascularisation (14%) and infiltrates (29%). Ulcerations were not detected. Although four out of 13 patients (31%) died of a cerebrovascular accident, the cause of cerebral apoplexy was thought not to be associated with the carotid bifurcation pathology. 'Re-boring' of occluding plaque, as in CEA, offers potential volumetric anatomical advantage over CSSA within the carotid bifurcation and bulb. In conclusion, precise and applied knowledge of carotid bifurcation anatomy is critical to reduce technical complications during CEA or CSSA. This information may reduce potential dangers of iatrogenic thrombo-embolism and ensuing neurologic deficits. Patients with low-grade carotid stenosis, evidence of focal plaque necrosis, are at risk of spontaneous plaque cap rupture, distal thromboembolism and stroke.
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Estenosis Carotídea/terapia , Anciano , Anciano de 80 o más Años , Angioplastia de Balón , Arteria Carótida Interna/anatomía & histología , Estenosis Carotídea/cirugía , Endarterectomía Carotidea , Femenino , Humanos , Masculino , Persona de Mediana Edad , StentsRESUMEN
Although pancreatic beta-cells are capable of adapting their mass in response to insulin requirements, evidence has shown that a dietary insult could compromise this ability. Fetal malnutrition has been linked to low birth weight and the development of type 2 diabetes later in life, while reduced beta-cell mass has been reported in adult rats fed a high-fat diet (HFD). Reported here are the effects of exposure to a HFD, during different periods of gestation, on neonatal rat weight and beta- and alpha-cell development. The experimental groups were composed of neonatal offspring obtained from Wistar rats fed a high-fat (40% as energy) diet for either the first (HF1), second (HF2), or third (HF3) week, or all three (HF1-3) weeks of gestation. Neonatal weights and circulating glucose and insulin concentrations were measured on postnatal day 1, after which the pancreata were excised and processed for histological immunocytochemical examination and image analysis. HF1 and HF2 neonates were hypoglycemic, whereas HF1-3 neonates were hyperglycemic. Low birth weights were observed only in HF1 neonates. No significant differences were detected in the circulating insulin concentrations in the neonates, although beta-cell volume and numbers were reduced in HF1-3 neonates. beta-cell numbers also declined in HF1 and HF3 neonates. alpha-cell volume, number and size were, however, increased in HF1-3 neonates. alpha-cell size was also increased in HF1 and HF3 neonates. In neonates, exposure to a maternal HFD throughout gestation was found to have the most adverse effect on beta-cell development and resulted in hyperglycemia.
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Animales Recién Nacidos/fisiología , Grasas de la Dieta , Islotes Pancreáticos/embriología , Animales , Glucemia , Femenino , Insulina/sangre , Islotes Pancreáticos/fisiología , Embarazo , Ratas , Ratas WistarRESUMEN
Transcription factors play an important role during pancreatic development ensuring normal differentiation of the islet endocrine cells. In mature beta-cells, expression of specific transcription factors is essential in maintaining normal beta-cell function.