A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods

The objective of this study is to compare the empirical allometric approaches with species invariant time methods using equivalent time, kallynochron, apolysichron, and dienetichrons. Pharmacokinetic parameters (clearance, volume of distribution, and elimination half-life) of ethosuximide, cyclosporine and ciprofloxacin were scaled-up from animal data obtained from the literature. Two methods were utilized to generate plots for the prediction of clearance in humans: (i) clearance versus body weight (simple allometric equation); and (ii) the product of clearance and maximum life-span potential (MLP) versus body weight. Plasma concentrations of each of the drugs were predicted using elementary and complex Dedrick plots, equivalent time with an exponent of 0.25 and equivalent time with the exponent obtained from the plot of body weight and half-life. Plasma concentrations of cyclosporine and ciprofloxacin were also predicted by MLP normalization (dienetichrons). Almost similar results in the pharmacokinetic parameters of the tested drugs were obtained by the allometric approach and by the species invariant time methods.     

Screening for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the commonest cancers in Asian males. In Malaysia, it is one of the ten most common cancers amongst the male population. Most of our patients with HCC present to us rather late and almost all die within 4 months of diagnosis. HCC occurs more commonly in patients with cirrhosis associated with hepatitis B and C infections. Screening for HCC can lead to early detection of small tumours (< 5 cm) that are more amenable to surgical resection, resulting in improved survival rates. The average 5-year survival rate for those who have undergone surgical resection is 68% (range, 22-73%). Better results are obtained with the smaller tumours (< 2 cm in diameter). Patients with chronic hepatitis B and C infection especially those who are > 45 years of age, who have concomitant cirrhosis or have a family history of HCC should be examined every 3-6 months with periodic serum alpha-fetoprotein (AFP) measurements and abdominal ultrasound examinations. Abdominal ultrasound is useful in the detection of small tumours. While mass screening for HCC is not cost-effective in countries of low incidence of HCC, screening of high risk groups may be justified in countries with a high endemicity of HBV infection. Screening for HCC in Japan, Taiwan and China appears to yield better results than those in the West. Nonetheless, primary prevention with mass hepatitis B vaccination and blood donor screening for anti-HCV is expected to make a much greater impact in the control of HCC in the years to come.     

Insulin-like growth factor I correlates with lean body mass in cystic fibrosis patients.

BACKGROUND: A major consequence of malnutrition in cystic fibrosis (CF) patients is the loss of lean body mass (LBM) and the subsequent impairment of respiratory muscle function. AIM: To determine whether insulin-like growth factor I (IGF-I) could be related to the LBM depletion and the evolution of respiratory disease in CF patients. METHODS: LBM was evaluated by dual energy x ray absorptiometry; serum concentrations of IGF-I were measured in 24 CF patients twice with a one year interval. Both values were expressed as SD score (SDS) calculated from normal data for age, sex, and pubertal stage and analysed with respect to anthropometric evaluation and disease related conditions. RESULTS: At the initial evaluation, IGF-I SDS had a mean value of -0.98 (range -3.6 to 3.2) and correlated with weight for age index, LBM SDS, and lung disease related conditions. Multiple regression analysis showed that only LBM remained independently related to IGF-I, suggesting that the relation of IGF-I to LBM was independent of weight and that the correlation between IGF-I and the respiratory conditions was related to the level of LBM. IGF-I SDS at the first evaluation was lower for the patients who lost > or =5% of weight for age index or > or =1 SD of LBM between the two evaluations. CONCLUSION: Low levels of IGF-I could be crucial for clinical outcome by impairing LBM and respiratory function. IGF-I could be a tool for nutritional evaluation by identifying the CF patients at risk of LBM depletion.     

Anatoxin-a(s), an anticholinesterase from the cyanobacterium Anabaena flos-aquae NRC-525-17

Anatoxin a(s) [antx-a(s)] given intraperitoneally to Sprague-Dawley rats at different doses (0.1-1.0 mg/kg) caused signs of severe cholinergic overstimulation. Assays of rat blood acetylcholinesterase (AChE) revealed a dose-dependent inhibition. The in vitro inhibition of electric eel acetylcholinesterase (AChE, E.C. 3.1.1.7) and horse serum butyrylcholinesterase (BUChE, E.C. 3.1.1.8) by antx-a(s) was time- and concentration-dependent. The inhibition of electric eel AChE follows first order kinetics, indicative of irreversible inhibition. The irreversibility of electric eel AChE inhibition was confirmed by a plot of Vmax versus total enzyme concentration [ET]. The kinetics of inhibition of cholinesterase by antx-a(s) supports the previous pharmacological findings that antx-a(s) is an anticholinesterase and that signs of intoxication by it are primarily due to cholinesterase inhibition.     

Post‐COVID‐19 splenic infarction in a patient with chronic atrial fibrillation: A case report

We describe splenic infarction (SI), an infrequent condition, in an 82‐year‐old COVID‐19 patient with chronic atrial fibrillation (AF). COVID‐19 may cause thrombosis, and AF is a predisposing factor for splenic infarction. Suspicion of SI may be warranted in COVID‐19 patients with abdominal pain, especially if a predisposing factor exists.     

Flexural Performance of Encased Pultruded GFRP I-Beam with High Strength Concrete under Static Loading

There is an interesting potential for the use of GFRP-pultruded profiles in hybrid GFRP-concrete structural elements, either for new constructions or for the rehabilitation of existing structures. This paper provides experimental and numerical investigations on the flexural performance of reinforced concrete (RC) specimens composite with encased pultruded GFRP I-sections. Five simply supported composite beams were tested in this experimental program to investigate the static flexural behavior of encased GFRP beams with high-strength concrete. Besides, the effect of using shear studs to improve the composite interaction between the GFRP beam and concrete as well as the effect of web stiffeners of GFRP were explored. Encasing the GFRP beam with concrete enhanced the peak load by 58.3%. Using shear connectors, web stiffeners, and both improved the peak loads by 100.6%, 97.3%, and 130.8%, respectively. The GFRP beams improved ductility by 21.6% relative to the reference one without the GFRP beam. Moreover, the shear connectors, web stiffeners, and both improved ductility by 185.5%, 119.8%, and 128.4%, respectively, relative to the encased reference beam. Furthermore, a non-linear Finite Element (FE) model was developed and validated by the experimental results to conduct a parametric study to investigate the effect of the concrete compressive strength and tensile strength of the GFRP beam. The developed FE model provided good agreement with the experimental results regarding deformations and damaged patterns.     

Role of second-line systemic treatment post-docetaxel in metastatic castrate resistant prostate cancer- current strategies and future directions

Treatment of metastatic castrate resistant prostate cancer (mCRPC) after progression on docetaxel chemotherapy is a challenging clinical scenario with limited availability of treatment options. Re-treatment with docetaxel, either as monotherapy or in combination with other cytotoxics or targeted agents has shown durable responses. However, most docetaxel re-treatment studies have been either retrospective or early phase non-randomised studies which have not formally assessed Quality of life or survival gain with re-treatment. Despite limited evidence for efficacy of mitoxantrone in the second-line, it continues to remain widely used, largely due to lack of available suitable alternatives. Cabazitaxel in combination with prednisolone is the only chemotherapy to have shown a significant survival benefit and receive approval by the U.S. Food and Drug Administration for patients with mCRPC previously treated with a docetaxel-based regimen. Abiraterone acetate has recently demonstrated a significant improvement in survival when compared to placebo in patients with docetaxel-treated mCRPC. This review aims to summarize the current evidence and discuss future strategies for treatment of mCRPC patients following failure of docetaxel chemotherapy.