Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers

The aims of this study were to determine the pharmacokinetic parameters of a single dose of 200 mg oral and rectal artesunate in healthy volunteers, and to suggest a rational dosage regimen for rectal administration. The study design was a randomized open cross-over study of 12 healthy volunteers; the analytical method used was a reversed phase high performance liquid chromatography with post column derivatization and subsequent ultraviolet detection. Pharmacokinetic parameters were derived from the main metabolite alpha-dihydroartemisinin data due to the rapid disappearance of artesunate from the plasma. Dihydroartemisinin following oral administration of artesunate had a significantly higher AUC(0-infinity) (P<0.05 95% confidence interval (CI) -1168.73, -667.61 ng x h/mL(-1)) and Cmax (P<0.05; 95% CI -419.73, -171.44 ng/mL(-1)), and had shorter tmax (P<0.05; 95% CI -0.97, -0.10 h) than that following rectal artesunate. There was no statistically significant difference in the elimination half-life between both routes of administration (P>0.05; 95% CI -0.14, 0.53 h). The relative bioavailability of rectal artesunate was [mean (coefficient of variation %) 54.9 (24.8%) %]. On the basis of these data an 8 hourly dosing regimen per day with rectal artesunate is proposed.     

Analysis of surgically-induced right bundle branch block pattern using intracardiac recording techniques.

Using intracardiac recording techniques, His bundle (H) and right ventricular apical (RVA) electrograms were recorded in 16 patients with a postoperative electrocardiographic pattern of right bundle branch block (RBBB). Their ages ranged from 5 to 12 years (mean 6.9 years) at surgery and the follow-up period was 1 to 7 years (mean 2.7 years). All were asymptomatic and in sinus rhythm at the time of study. The P-A interval was normal in all and the A-H, H-V, and V-RVA intervals were prolonged in one, one, and six patients, respectively. The V-RNA interval was normal (less than or equal to 30 msec) in ten out of the 11 patients (91%) without associated left anterior hemiblock (LAH), indicating a physiologically intact main right bundle branch, and was abnormally lengthened (45-62 msec) in all five patients (100%) with associated LAH. These findings suggest that there are two subgroups of patients with surgicall-induced RBBB pattern and the measurement of the V-RVA interval in conjunction with the H-V interval may be of ultimate importance in understanding the long-term prognostic implication of surgically-induced RBBB pattern with or without LAH.     

Impact of Intracranial Pressure Monitor–Guided Therapy on Neurologic Outcome After Spontaneous Nontraumatic Intracranial Hemorrhage

Objectives: Intracranial pressure (ICP) monitors have been used in some patients with spontaneous intracranial hemorrhage (ICH) to provide information to guide treatment without clear evidence for its use in this population. We assessed the impact of ICP monitor placement, including external ventricular drains and intraparenchymal monitors, on neurologic outcome in this population.Materials and MethodsIn this secondary analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation III trial, the primary outcome was poor outcome (modified Rankin Scale score 4-6) and the secondary outcome was death, at 1 year from onset. We compared outcomes in patients with or without an ICP monitor using unadjusted and adjusted logistic regression models. The analyses were repeated in a balanced cohort created with propensity score matching.ResultsSeventy patients underwent ICP monitor placement and 424 did not. Poor outcome was seen in 77.1% of patients in the ICP-monitor subgroup compared with 53.8% in the no-monitor subgroup (p<0.001). Of patients in the ICP-monitor subgroup, 31.4% died, compared with 21.0% in the no-monitor subgroup (p=0.053). In multivariate models, ICP monitor placement was associated with a >2-fold greater risk of poor outcome (odds ratio 2.76, 95% CI 1.30–5.85, p=0.008), but not with death (p=0.652). Our findings remained consistent in the propensity score-matched cohort.ConclusionThese results question whether ICP monitor–guided therapy in patients with spontaneous nontraumatic ICH improves outcome. Further work is required to define the causal pathway and improve identification of patients that might benefit from invasive ICP monitoring.     

Efficacy of early treatment with toltrazuril in prevention of coccidiosis and necrotic enteritis in chickens

In the present study, efficacy of the toltrazuril treatment for prevention of coccidiosis and necrotic enteritis was tested. Ninety-six 14-day-old commercial broiler chickens were caged and divided into eight groups (n=12), designated groups 1 to 8. Chickens of groups 1 to 6 were inoculated orally at 18 days of age with 25,000 oocysts of Eimeria tenella and 75,000 oocysts of Eimeria brunetti. At 22 days of age, chickens of groups 1 to 6 were infected with 10⁹ colony-forming unit Clostridium perfringens. Chickens of group 1 were treated with 75 parts/10⁶ toltrazuril in drinking water for 8 h on two consecutive days up to 12 h before Eimeria infection, while chickens of groups 2 to 5 were treated with the same dose of toltrazuril at 12 h, 36 h, 60 h and 84 h after Eimeria infection, respectively. The non-treated group 6 served as a positive control. Chickens in group 7 were treated with toltrazuril at 17 and 18 days of age, and those of group 8 remained uninfected and non-treated as a negative control. The feed conversion ratio was higher in the positive control compared with other groups. The mortality rates were 16.8% and 41.7% in the late toltrazuril-treated (at 84 h) and infected non-treated chickens, respectively. Lesions scores of necrotic enteritis or coccidiosis in infected, non-treated chickens were significantly more severe compared with negative controls (P<0.01) and late toltrazuril-treated (at 84 h) chickens (P<0.05). In conclusion, application of toltrazuril before Eimeria challenge protected chickens from coccidiosis and indirectly from successive necrotic enteritis caused by C. perfringens infection.     

Computed tomographic scan mapping of gastric wall perfusion and clinical implications

Background

Several postoperative gastrointestinal complications are attributed to ischemia. We herein evaluate the gastric wall perfusion using computed tomography (CT) scan perfusion index on trial to address the etiology of ischemic complication after sleeve gastrectomy.

Methods

A retrospective study of 205 patients undergoing CT scan of the abdomen to evaluate the pattern of gastric vascular perfusion was performed. The perfusion index of the gastric mucosa was measured at 5 gastric points using CT perfusion scanning.

Results

Gastric perfusion at the angle of His (AOH) (53.51 ± 14.38) was statistically significantly lower (P < .001) than that at the other gastric points studied: fundus, greater curvature, lesser curvature, incisura angularis, and mid gastric points (76.16 ± 15.21, 73.27 ± 16.55, 76.12 ± 16.12, and 75.24 ± 14.9, respectively). Gastric perfusion was significantly lower at all the gastric points (and especially so at the AOH) among obese patients (33 cases) compared with nonobese patients (18 cases). Gastric perfusion at all the points studied showed a decrease as the body mass index increases. Hypertensive patients had a better gastric perfusion compared with nonhypertensive patients.

Conclusions

Gastric wall perfusion is statistically significantly decreased at the AOH and gastric fundus compared with perfusion at other gastric points. Gastric perfusion at all the gastric points studied decreased with the increase in body mass index. Gastric leakage in obese patients following sleeve gastrectomy could be attributed to a decrease in the blood supply at AOH.     

Parathyroid hormone 1–34 enhances extracellular matrix deposition and organization during flexor tendon repair

Parathyroid hormone (PTH) 1–34 is known to enhance fracture healing. Tendon repair is analogous to bone healing in its dependence on the proliferation and differentiation of mesenchymal stem cells, matrix formation, and tissue remodeling.^1,2,3 We hypothesized that PTH 1–34 enhances tendon healing in a flexor digitorum longus (FDL) tendon repair model. C57Bl/6J mice were treated with either intraperitoneal PTH 1–34 or vehicle‐control (PBS). Tendons were harvested at 3–28 days for histology, gene expression, and biomechanical testing. The metatarsophalangeal joint range of motion was reduced 1.5–2‐fold in PTH 1–34 mice compared to control mice. The gliding coefficient, a measure of adhesion formation, was 2–3.5‐fold higher in PTH 1–34 mice. At 14 days post‐repair, the tensile strength was twofold higher in PTH 1–34 specimens, but at 28 days there were no differences. PTH 1–34 mice had increased fibrous tissue deposition that correlated with elevated expression of collagens and fibronectin as seen on quantitative PCR. PTH 1–34 accelerated the deposition of reparative tissue but increased adhesion formation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:17–24, 2015.     

Combination of phytosterols and omega-3 fatty acids: a potential strategy to promote cardiovascular health

Phytosterols and omega-3 fatty acids (n-3) are natural food ingredients with potential cardiovascular benefits. Phytosterols inhibit cholesterol absorption, thereby reducing total cholesterol (TC) and LDL-cholesterol levels. Numerous clinical studies have shown that a daily intake of 1.5-2.0 g of phytosterols can result in a 10-15 % reduction in LDL levels, while consumption of n-3 is associated with a significant reduction in plasma triglyceride (TG) concentrations. Furthermore, n-3 may also beneficially modify a number of other risk factors of coronary heart disease (CHD). Thus, it is reasonable to suggest that combination of phytosterols and n-3 may further reduce cardiovascular risk factors. Esterification of phytosterols with non-n-3 fatty acids has substantially improved their incorporation into a variety of foods without affecting the efficacy of phytosterols. Therefore, it is assumed that esterification of phytosterols with n-3 may have advantages for both food industry and health. Evidence suggests that this combination is effective in reducing the levels of several cardiovascular risk factors including TC and TG concentrations, pro-aggregatory factors, arrhythmic eicosanoid and thromboxane A2 levels. In this mini-review, we have critically reviewed and summarized data from clinical and animal studies in which phytosterols and n-3, alone or in combination, were used. We have also provided information on structure-function relationship for these two natural compounds. Biological properties of several phytosterol derivatives including phytosterol-glucoside have been also discussed. Although the animal studies are supportive of this combination therapy, human studies are needed to address its long term effects.     

Left superior vena cava isolation in patients undergoing pulmonary vein antrum isolation: impact on atrial fibrillation recurrence.

BACKGROUND: A persistent left superior vena cava (SVC) can be an arrhythmogenic source in patients with atrial fibrillation (AF) through connections from the coronary sinus (CS) and the left atrium (LA). The left SVC can be electrically isolated. However, little clinical data about the impact of left SVC disconnection on AF outcome are available. We report on six patients with left SVC and recurrent AF. OBJECTIVES: The purpose of this study was to assess the impact of left SVC isolation on AF recurrence. METHODS: Six patients (4 men and 2 women; age 50 +/- 6.4 years) with symptomatic drug-refractory AF and persistent left SVC presented to our laboratory for treatment. Four of the patients had left SVC isolation only because there was no conduction recovery in the pulmonary veins (PVs) after several previous procedures. RESULTS: Conduction between the left SVC and the CS and LA was documented, as was spontaneous ectopies in three patients that degenerated into AF in one patient. Isolation of the left SVC was successful in all patients. Isolation was relatively easy to perform (10.25 +/- 1.6 minutes), with no complications. After follow-up of 13 +/- 7.4 months, all patients were in sinus rhythm and free from AF without antiarrhythmic drugs. CONCLUSION: This study stresses the importance of looking for unusual sources of AF in patients presenting for repeat procedures or in those in whom the PVs have been ruled out as a source triggering AF. We present clinical evidence that in patients with AF and left SVC, isolation of the PVs only may not be sufficient to suppress AF. Thus, diagnosis and isolation of the left SVC appears critical to preventing AF recurrence in patients with AF when ablation is considered.