1,721,002 research outputs found
Compound action potential of sensory tail nerves in the rat
No full textAssessment of the conduction velocity of motor fibers of the rat tail nerves has been used by some authors in the past, but very little is known
about the sensory fibers. In 10 adult rats, weighing between 320 and 380 g, responses from the nerves and muscles of the tail have been recorded
after stimulation at its root and tip. It was found that stimulation of the tip involved mainly sensory fibers, of which two main groups could be
identified. One faster group, conducting within the range of 38–27 m/s, and one slower group with range 14–7 m/s. The bipolar recording
configuration was found to be optimal for sensory recording. Stimulation of the tail root evoked a motor response, which was preceded by a very
small neurographic activity, due to the fastest sensory fibers conducting antidromically. The conduction velocity of motor fibers was calculated to
be approximately 19 m/s. Distance traveled by the volley can be assessed with excellent precision on the tail nerves; hence the calculated
conduction velocities are highly reliable and reproducible. We propose that the tail nerves may be a useful tool for evaluation of conduction
velocity of Aβ and Aδ afferents. As the technique is just minimally invasive, the test can be repeated a number of times in animals under chronic
experimental conditions
Ivermectin concentration in breastmilk of a woman with Strongyloides stercoralis and human T-lymphotropic virus-I co-infection
No full textIvermectin is a widely used drug for the treatment of various neglected tropical diseases, such as lymphatic filariasis, onchocerciasis, and strongyloidiasis among others. Despite its excellent safety profile, there are few published studies of the use of ivermectin in children, pregnant and nursing women. In the present study, we report clinical data on ivermectin concentrations in breastmilk of a woman with Strongyloides stercoralis and HTLV-I coinfection. Ivermectin levels in breastmilk ranged from 1.4 to 20.8 ng/ml, with a mean of 9.26 ng/ml after a single dose of 200 μg/kg. We estimated the possible ivermectin exposure of the infant to be 1.1 μg/kg, 0.55% of the weight-adjusted percentage of the maternal dose. This value is largely under the threshold established by the World Health Organization for safe breastfeeding. Our results bolster previous findings on the secretion of ivermectin into breastmilk in healthy volunteers. The findings from this case study do not support exclusion of lactating women or interrupting lactation to accommodate it
Clinical effectiveness of Lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia
No full textA new plasma ceramide 24-based risk score predicts overall mortality and nonfatal myocardial infarction in patients with suspected or known coronary artery disease
No full textBackground and aim: Plasma ceramides (Cer) are associated with adverse cardiovascular outcomes in patients with coronary artery disease (CAD). We examined whether a newly developed plasma ceramide-based risk score (CER24 score) performs better than CERT1 risk score in predicting adverse cardiovascular outcomes in patients with known or suspected CAD. Methods and results: We followed 167 ambulatory patients undergoing stress myocardial perfusion scintigraphy (MPS) for clinical reasons for a median of 6 years. For the CER24 risk score calculation, we measured plasma Cer(d16:1/24:1)/Cer(d16:1/24:0), Cer(d18:0/24:1)/Cer(d18:0/24:0), Cer(d18:1/24:1)/Cer(d18:1/24:0), Cer(d18:2/24:1)/Cer(d18:2/24:0), and Cer(d20:1/24:1)/Cer(d20:1/24:0), both before and after stress MPS, using a targeted liquid chromatography-tandem mass spectrometry assay. Pre-stress CER24 risk categories (high vs. low/moderate risk) at baseline were associated with a ∼3-fold higher risk of developing the primary composite outcome (defined as all-cause mortality or nonfatal myocardial infarction) even after adjustment for age, sex, smoking, diabetes, pre-existing CAD, left ventricular ejection fraction, and stress-induced inducible myocardial ischemia on MPS (adjusted-hazard ratio 3.06, 95 %CI 1.63-5.77; p = 0.001). Post-stress CER24 risk categories yielded similar results. CER24 high-risk category performed better than CERT1 high-risk category in predicting the primary composite outcome (AUCs = 0.647 vs. 0.580; p = 0.048). Conclusions: The CER24 score is associated with a higher risk of the composite outcome and performs better than CERT1 score in predicting the risk of dying or developing nonfatal cardiovascular events
Influence of trastuzumab on epirubicin pharmacokinetics in metastatic breast cancer patients
No full textBackground: Anthracycline cardiotoxicity is increased by the contemporaneous administration of trastuzumab. The mechanism by which it occurs is as yet unknown. The aim of this study was to evaluate whether
trastuzumab modifies the pharmacokinetics of epirubicin and its metabolites.
Patients and methods: Women with HER2-positive metastatic breast cancer were treated with epirubicin
75 mg/m2
i.v. bolus followed by docetaxel 75 mg/m2
in a 1-h infusion, every 3 weeks for six cycles, and trastuzumab (once at 4 mg/m2
, then 2 mg/m2
weekly thereafter) in a 30-min infusion. Epirubicin pharmacokinetic
data of seven patients were evaluated at the first cycle of therapy (baseline, with trastuzumab administered 24 h
after epirubicin), and at the sixth cycle (i.e. 15 weeks after baseline, with trastuzumab administered immediately before epirubicin).
Results: No pharmacokinetic change in the parent compound epirubicin was detected. The area under the
plasma concentration–time curve (AUC0–24 h) was 1230 ± 318 [mean ± standard deviation (SD)] at the first
cycle and 1287 ± 385 h·μg/l at the sixth. The mean (±SD) maximum plasma concentration (Cmax) and the terminal elimination half-life at the first cycle (1303 ± 490 μg/l and 12.5 ± 3.1 h, respectively) were similar to those
obtained at the sixth cycle (1229 ± 580 μg/l and 11.5 ± 2.9 h, respectively). Pharmacokinetic data of epirubicin
metabolites evaluated at the first and sixth cycle of chemotherapy were superimposable without any statistical
difference.
Conclusion: Enhanced anthracycline cardiotoxicity related to trastuzumab administration was not linked to
pharmacokinetic interferences with epirubicin and its metabolite
Association between KLF6 rs3750861 polymorphism and plasma ceramide concentrations in post-menopausal women with type 2 diabetes
No full textBackground and aim: Based on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM). Methods and result: We measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system. Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 μmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 μmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 μmol/L, p = 0.032) compared with those with C/C genotype. Conclusions: The C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM
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