Interaction between theophylline and oestrogen in the rat uterus

Theophylline alone or in the presence of 0.001, 0.01, 0.1 or 1 microgram oestradiol-17 beta/100 g body wt increase uterine RNA and protein content 6 h after administration. Uterine oedema induced by physiological doses of oestradiol-17 beta was increased further in the presence of theophylline. Theophylline decreased the number of eosinophils in the blood and concurrently decreased oestrogen-induced uterine oesinophilia at doses of 0.01, 0.1, 1, 10 or 30 micrograms oestradiol-17 beta/100 g body wt. Oestrogen binding by uterine eosinophils in vitro increased in the presence of theophylline. This effect of theophylline could explain the increase of oestrogen-induced uterine oedema in vivo.     

Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses

OBJECTIVE: To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses. METHOD: After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72h after the last active dose. RESULTS: Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14-16%, 72h after the last active dose. CONCLUSION: This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36h after the last active dose.     

Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death

OBJECTIVE: Autoantibodies to DNA topoisomerase I (topo I) are associated with diffuse systemic sclerosis (SSc), appear to be antigen driven, and may be triggered by cryptic epitopes exposed during in vivo topo I fragmentation. These autoantibodies recognize topo I and fragments of this autoantigen generated during apoptosis and necrosis. We undertook this study to determine whether lysosomal cathepsins are involved in topo I fragmentation during necrosis. METHODS: Topo I cleavage during necrosis was assessed by immunoblotting of lysates from L929 fibroblasts exposed to tumor necrosis factor alpha (TNFalpha) and the broad caspase inhibitor Z-VAD-FMK, and by immunoblotting of lysates from endothelial cells treated with HgCl2. Purified topo I and L929 nuclei were incubated with cathepsins B, D, G, H, and L, and topo I cleavage was detected by immunoblotting. The intracellular localization of cathepsin L activity and topo I in necrotic cells was examined using fluorescence microscopy. RESULTS: Treatment of L929 cells with TNFalpha and Z-VAD-FMK induced caspase-independent cell death with necrotic morphology. This cell death involved topo I cleavage into fragments of approximately 70 kd and 45 kd. This cleavage profile was reproduced in vitro by cathepsins L and H and was inhibited by the cathepsin L inhibitor Z-FY-CHO. During necrosis, cathepsin L activity diffused from lysosomes into the cytoplasm and nucleus, whereas topo I partially relocalized to the cytoplasm. Z-FY-CHO delayed necrosis and partially blocked topo I cleavage. The topo I cleavage fragments were also detected in necrotic endothelial cells and recognized by SSc sera containing anti-topo I antibodies. CONCLUSION: These results implicate cathepsins, particularly cathepsin L, in the cleavage of topo I during necrosis. This cleavage may generate potentially immunogenic fragments that could trigger anti-topo I immune responses in SSc.     

Targeting the Dopaminergic System in Autoimmunity

Journal of Neuroimmune Pharmacology - Dopamine has emerged as a fundamental regulator of inflammation. In this regard, it has been shown that dopaminergic signalling pathways are key players...     

Further insecticidal activities of essential oils from Lippia sidoides and Croton species against Aedes aegypti L.

This study assessed new insecticidal activities of essential oils from Lippia sidoides and Croton species (Croton zehntneri, Croton nepetaefolius, Croton argyrophylloides, and Croton sonderianus) against Aedes aegypti mosquito. In addition, the acute toxicity upon mice was determined. All essential oils showed inhibition of egg hatching, with IC₅₀ values ranging from 66.4 to 143.2 μg?mL^?1, larvicidal activity with LC₅₀ ranging from 25.5 to 94.6 μg?mL^?1, and pupicidal action with PC₅₀ ranging from 276.8 to over 500 μg?mL^?1. Only L. sidoides, C. zehntneri, and C. argyrophylloides essential oils were able to inhibit the oviposition of female gravid mosquitoes with OD₅₀ values of 35.3, 45.3, and 45.8 μg?mL^?1, respectively. Oral acute toxicity in mice showed that C. sonderianus and C. argyrophylloides oils are nontoxic (LD₅₀?>?6,000 mg.kg^?1) while C. nepetaefolius, C. zehntneri, and L. sidoides oils are moderately toxic (LD₅₀ 3,840; 3,464, and 2,624 mg.kg^?1, respectively). The results indicate that these oils are promising sources of bioactive compounds, showing low or no toxicity to mammals.     

Synergistic potential of 1α,25-dihydroxyvitamin D3 and calcium–aluminate–chitosan scaffolds with dental pulp cells

Clinical Oral Investigations - This study aimed to develop a porous chitosan–calcium–aluminate scaffold (CH-AlCa) in combination with a bioactive dosage of 1α,25-dihydroxyvitamin...     

Transient neonatal diabetes due to a missense mutation (E227K) in the gene encoding the ATP‐sensitive potassium channel (KCNJ11)

Neonatal diabetes is a monogenic form of diabetes. Herein, we report on a newborn presenting diabetic ketoacidosis at 17 days of life . A KCNJ11 mutation was identified. In such cases, insulin can be replaced by sulfonylurea with a successful metabolic control, as an example of how molecular diagnosis may influence the clinical management of the disorder.     

Diagnosis and management of hepatic artery in-stent restenosis after liver transplantation by optical coherence tomography:A case report

BACKGROUND Percutaneous transluminal angioplasty and stenting represent an effective treatment for hepatic artery stenosis after liver transplantation. In the first year after stenting, approximately 22% of patients experience in-stent restenosis, increasing the risk of artery thrombosis and related complications, and 50% experience liver failure. Although angiography is an important tool for diagnosis and the planning of therapeutic interventions, it may raise doubts, especially in small-diameter arteries, and it provides low resolution rates compared with newer intravascular imaging methods, such as optical coherence tomography(OCT).CASE SUMMARY A 64-year-old male developed hepatic artery stenosis one year after orthotropic liver transplantation and was successfully treated with percutaneous transluminal angioplasty with stenting. Five months later, the Doppler ultrasound results indicated restenosis. Visceral arteriography confirmed hepatic artery tortuosity but was doubtful for significant in-stent restenosis(ISR) and intrahepatic flow reduction. To confirm ISR, identify the etiology and guide treatment, OCT was performed. OCT showed severe stenosis due to four mechanisms: Focal and partial stent fracture, late stent malapposition, in-stent neointimal hyperplasia, and neoatherosclerosis.CONCLUSION Intravascular diagnostic methods can be useful in evaluating cases in which initial angiography results are not sufficient to provide a proper diagnosis of significant stenosis, especially with regard to ISR. A wide range of diagnoses are provided by OCT, resulting in different treatment options. Interventional radiologists should consider intravascular diagnostic methods as additional tools for evaluating patients when visceral angiography results are unclear.     

Description and molecular characterization of Haemoproteus macrovacuolatus n. sp. (Haemosporida,Haemoproteidae), a morphologically unique blood parasite of black-bellied whistling duck (Dendrocygna autumnalis) from South America

During a surveillance programme on avian influenza in wild birds in the east of Colombia, 42 % of examined wild black-bellied whistling ducks (Dendrocygna autumnalis) were infected with undescribed Haemoproteus sp., which macrogametocytes possess one or several huge (2.5 μm in largest diameter) conspicuous roundish vacuoles, a unique character of avian haemoproteids. This parasite is named Haemoproteus (Parahaemoproteus) macrovacuolatus and described here using data on the morphology of its gametocytes, host cells and sequences of the complete mitochondrial genome and cytochrome b fragments. Illustrations of blood stages of the new species and DNA sequence information are provided. The phylogenetic analysis identified a closely related lineage C033, reported in South Asian ducks belonging to Dendrocygna. We also found that all Haemoproteus lineages from Passeriformes conformed a monophyletic group. Whereas we cannot exclude that this pattern could be an artefact of the limited taxonomic sampling in non-passeriform birds, thus this finding is worthy of attention. This study adds to our knowledge of the phylogenetic relationships among species of avian haemoproteids and describes a new haemoparasite in a non-passerine host.