Current Issue : October - December Volume : 2014 Issue Number : 4 Articles : 6 Articles
The aim of this study was to explore effects on anxiety-like behavior of D1 dopamine receptor agonist, SKF-38393, and of\nD1 dopamine receptor antagonist, SCH-23390, given alone or in combination with a low dose of 17????-estradiol (17????-E2) to\novariectomized (OVX) rats. Two weeks after surgery, OVX rats began 14 days of treatment with the vehicle, a low dose of 17????-\nE2 (5.0 ????g/rat, s.c.), SKF-38393 (0.1mg/kg, i.p.), SCH-23390 (0.1mg/kg, i.p.), SKF-38393 plus 17????-E2, or SCH-23390 plus 17????-\nE2. The animals were tested in the black and white model (BWM) and the open field test (OFT). SCH-23390 (0.1mg/kg, i.p.)\nalone or in a combination with a low dose of 17????-E2 (5.0 ????g/rat, s.c.) resulted in anxiolytic-like effect in OVX rats in the BWM.\nRepeated treatment with SCH-23390 and 17????-E2 profoundly increased anxiolytic-like effect of single substances exerted per se.\nCoadministration of SCH-23390 with 17????-E2 increased frequency of rearing and grooming in OVX rats in OFT. SKF-38393\n(0.1mg/kg, i.p.) treatment failed to alter anxiety-like behavior in OVX rats in the BWM. The results of the present study suggest\nthat 17????-E2 and SCH-23390 interact to exert anxiolytic-like action and that each of these drugs can potentiate effects of each other....
Objective. To evaluate the efficacy and safety of the telmisartan plus amlodipine (T/A) single-pill combination (SPC) in Asian\npatients with hypertension whose blood pressure (BP) was not adequately controlled on either monotherapy or on low-dose\ncombination therapy. Patients and Methods. Data are presented from five Boehringer Ingelheim-sponsored phase 3, double-blind,\n8-week, studies: two studies in nonresponders to amlodipine (data pooled for amlodipine), two studies on nonresponders to\ntelmisartan (pooled data), and one on nonresponders to low-dose T/A SPC. Results. After 8 weeks� treatment, mean reductions\nfrom the reference baseline in diastolic BP (DBP; primary endpoint), systolic BP (SBP), and SBP, DBP goal, and response rates\nwere higher with the T/A SPC than respective monotherapies. The T80/A5 SPC resulted in greater reductions in DBP and SBP,\nand higher DBP goal and response rate than the low-dose T40/A5 SPC. Peripheral edema incidence was low (amlodipine 0.5%,\ntelmisartan 0.0%, and T/A SPC 0.7%). Discussion and Conclusion. In Asian patients whose BP is not adequately controlled with\ntelmisartan or amlodipine monotherapy, T/A SPC treatment results in greater BP reduction, and higher DBP and SBP goal and\nresponse rates. The safety and tolerability of the T/A SPC are comparable to those of the respective monotherapies and consistent\nwith those reported in previous studies....
Erdheim-Chester disease (ECD) is a rare multisystem non-Langerhans histiocytosis. CNS involvement is a major complication,\nwhich is often rapidly progressive and confers a poor prognosis. However, treatment of CNS ECD is difficult due to poor CNS\npenetrance by the most effective chemotherapeutic drugs commonly used in this disorder (e.g., interferon and cladribine). We\ndescribe a case of a 60-year-old lady with a 5-year history of stable systemic ECD who presented with new brainstem lesions and\nrapid, steroid-refractory neurological deterioration which required immediate intervention. High-dose methotrexate was chosen\ndue to its rapid onset of action and excellent CNS penetration. Her neurological deterioration was quickly arrested with significant\nfunctional improvement, which was sustained for 4 months with consolidation doses of high-dose methotrexate. Subsequent\ntreatment with cladribine and interferon did not confer any appreciable clinical improvement. High-dose methotrexate is effective\nin controlling rapidly progressive CNS ECD and should be considered as a salvage agent prior to commencement ofmore definitive\ntreatment....
Polymyositis is a rare debilitating condition characterized by chronic inflammation and muscle weakness. Standard treatments\ninclude corticosteroids and immunosuppressants; however, resistance to these regimens may develop. Intravenous immunoglobulins\n(IVIg) are thus recommended for patients with drug-resistant polymyositis. The patient presented a resistant polymyositis with\nseveremuscle weakness, increasing dysphagia, and significant loss in weight. Subcutaneous immunoglobulins (SCIg) were initiated\nafter failure of steroids and immunosuppressive drugs. SCIg was given twice per week (2 then 1.3 g/kg/month). Clinical recovery\nwas observed within 2 months after the SCIg initiation. After several injections, the patient showed a progressive improvement in\nmuscle strength. Serum creatine kinase activity decreased to normal levels, and dysphagia was resolved. The SC injections were\ngenerally well tolerated and good patient satisfaction was reported. This promising observation suggests that SCIg may be useful\nin active and refractory polymyositis....
This present paper presents an analytical description and numerical simulations of the influence of macroscopic intercell dose\nvariations and intercell sensitivity variations on the probability of controlling the tumour. Computer simulations of tumour control\nprobability accounting for heterogeneity in dose and radiation sensitivity were performed. An analytical expression for tumor\ncontrol probability accounting for heterogeneity in sensitivity was also proposed and validated against simulations. The results\nshow good agreement between numerical simulations and the calculated TCP using the proposed analytical expression for the\ncase of a heterogeneous dose and sensitivity distributions.When the intratumour variations of dose and sensitivity are taken into\naccount, the total dose required for achieving the same level of control as for the case of homogeneous distribution is only slightly\nhigher, the influence of the variations in the two factors taken into account being additive.The results of this study show that the\ninterplay between cell or tumour variation in the sensitivity to radiation and the inherent heterogeneity in dose distribution is\nhighly complex and therefore should be taken into account when predicting the outcome of a given treatment in terms of tumor\ncontrol probability....
Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation\nmodulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose\ndecitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however,\nthey are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of\nDNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a\nnew treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based\nchemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our\ntrial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort\nwas optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous\ntreatment. We also identified a significant correlation between the PFS to previous treatment and clinical response.The low-dose\nDAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients\nwith refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083)....
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