Erucin,a new promising cancer chemopreventive agent from rocket salads,shows anti-proliferative activity on human lung carcinoma A549 cells

Erucin (ER) is a dietary isothiocyanate present in cruciferous vegetables, such as rocket salads (Erucasativa Mill., Diplotaxis sp.), that has been recently considered a promising cancer chemopreventive phytochemical. Biological activity of ER was investigated on human lung adenocarcinoma A549 cells, analyzing its effects on molecular pathways involved in apoptosis and cell cycle arrest, such as PARP-1 cleavage, p53 and p21 protein expression. Our results show that ER affects the A549 cell proliferation, enhancing significantly p53 and p21 protein expression in a dose-dependent manner (p < 0.001). PARP-1 cleavage occurs only after exposure to high concentrations of ER (50 μM), in accordance to previous studies showing similar bioactivity of other isothiocyanates (ITCs). Our study reports for the first time that the induction of p53, p21 and PARP-1 cleavage may participate in the anti-proliferative activity of ER in human lung adenocarcinoma A549 cells. Comparison of data with those obtained with the isothiocyanate sulforaphane (SF), structurally related to ER, underlines the strong relationship between structural analogy of ITCs and their biological activity. The ability of dietary compounds to modulate molecular mechanisms that affect cancer cell proliferation is certainly a key point of the cancer prevention potential by functional foods.     

The kinetics of cohesive powder de-agglomeration from three inhaler devices

Purpose

The purpose of the current investigation is to understand the kinetics of de-agglomeration (k_d) of micronised salbutamol sulphate (SS) and lactohale 300 (LH300) under varying air flow rates (30-180 l min⁻¹) from three dry powder inhaler devices (DPIs), Rotahaler^® (RH), Monodose Inhaler^® (MI) and Handihaler^® (HH).

Results

Cumulative fine particle mass vs. time profiles were obtained from the powder concentration, emitted mass and volume percent <5.4 μm, embedded in the particle size distributions of the aerosol at specific times. The rate of de-agglomeration (k_d), estimated from non-linear least squares modelling, increased with increasing air flow rates. The k_dvs. air flow rate profiles of SS and LH300 were significantly different at high air flow rates. The k_d was highest from RH and lowest from MI. Differences in k_d between the devices were related to device mode of operation while the differences between the materials were due to the powder bed structure.

Conclusion

This approach provided a methodology to measure the rate constant for cohesive powder de-agglomeration following aerosolisation from commercial devices and an initial understanding of the influence of device, air flow rate and material on these rate constants.     

Newborn length predicts early infant linear growth retardation and disproportionately high weight gain in a low-income population

Background

Stunting is prevalent by the age of 6 months in the indigenous population of the Western Highlands of Guatemala.

Aim

The objective of this study was to determine the time course and predictors of linear growth failure and weight-for-age in early infancy.

Study design and subjects

One hundred and forty eight term newborns had measurements of length and weight in their homes, repeated at 3 and 6 months. Maternal measurements were also obtained.

Results

Mean ± SD length-for-age Z-score (LAZ) declined from newborn − 1.0 ± 1.01 to − 2.20 ± 1.05 and − 2.26 ± 1.01 at 3 and 6 months respectively. Stunting rates for newborn, 3 and 6 months were 47%, 53% and 56% respectively. A multiple regression model (R² = 0.64) demonstrated that the major predictor of LAZ at 3 months was newborn LAZ with the other predictors being newborn weight-for-age Z-score (WAZ), gender and maternal education ∗ maternal age interaction. Because WAZ remained essentially constant and LAZ declined during the same period, weight-for-length Z-score (WLZ) increased from − 0.44 to + 1.28 from birth to 3 months. The more severe the linear growth failure, the greater WAZ was in proportion to the LAZ.

Conclusion

The primary conclusion is that impaired fetal linear growth is the major predictor of early infant linear growth failure indicating that prevention needs to start with maternal interventions.     

CLINICAL APPLICATION OF THE RIGHT SIDELYING RESPIRATORY LEFT ADDUCTOR PULL BACK EXERCISE

Problem:

Lumbopelvic‐femoral conditions are common and may be associated with asymmetrical musculoskeletal and respiratory impairments and postural mal‐alignment called a Left Anterior Interior Chain (AIC) pattern. An inherent pattern of asymmetry involves the trunk/ribs/spine/pelvis/hip joints and includes the tendency to stand on the right leg and shift the center of gravity to the right which may result for example, in a tight left posterior hip capsule, poorly approximated left hip, long/weak left adductors, internal obliques (IO) and transverse abdominus (TA), short/strong/over active paraspinals and muscles on the right anterior outlet (adductors, levator ani and obturator internus), a left rib flare and a decreased respiratory diaphragm zone of apposition (ZOA).

The Solution:

A therapeutic exercise technique that can address impairments associated with postural asymmetry may be beneficial in improving function, reducing and/or eliminating pain causation, and improving breathing. The Right Sidelying Left Respiratory Adductor Pull Back is an exercise designed to affect alignment of the lumbopelvic‐femoral region by influencing the left posterior ischiofemoral ligament, ZOA and right anterior outlet and left anterior inlet (rectus femoris, sartorius), activating/shortening the left adductors, left IO/TA''s and inhibiting/lengthening the paraspinals, bilaterally.

Discussion:

The exercise technique is often used by Physical Therapists, Physical Therapist assistants and Athletic Trainers as an initial exercise to positively affect position/alignment of the lumbopelvic‐femoral region, referred to as “repositioning,” by clinicians who use it. Four published case studies have used similar exercises to address the above impairments associated with a Left AIC pattern and in each 100% improvement in function and pain intensity was described. This particular exercise technique is relatively new and warrants future research.     

Capacity-limited elimination of cefmetazole in rat

Elimination kinetics of cefmetazole (CMZ) in the rat is studied with changing the dosing amount (D). The normalized area under plasma concentration-time curve (AUC/D) and the mean residence time (MRT) increase with increasing amount of i.v. dose of CMZ. These increases prove the capacity-limited elimination of CMZ without regard to any pharmacokinetic model. The apparent steady-state volume of distribution (V^a_ss) which is defined by D β MRT/AUC is almost independent of D. The simultaneous multi-lines fitting using time course curves following different doses is also attempted to determine the pharmacokinetic model by the application of the minimum AIC estimation (MAICE). AIC, consequently, shows the minimum for the two-compartment model with the Michaelis-Menten elimination. The Y_ss estimated from this model is about 450 ml/kg which agrees with V^a_ss estimated by moment analysis.     

Evaluation of analyses of univariate discrete twin data

Akiake's Information Criterion (AIC) is commonly used in univariate twin modeling of a discrete trait to prune a full model into a more parsimonious submodel. It is possible that this practice could introduce bias and inaccuracy, and we could identify no prior systematic study of these issues. Thus, we used simulation to investigate the performance of AIC-guided modeling across a broad range of parameters. Our simulations indicated that the use of the AIC to determine the best univariate model for a discrete trait tended to yield the incorrect model rather frequently. Moreover the parameter estimates of the best model by AIC were biased sharply upward as were the associated 95% confidence intervals. These results suggest that the use of AIC to guide twin modeling for univariate discrete traits should either be abandoned or used with great caution.     

Analysis of enterohepatic circulation of cefixime in rat by fast inverse Laplace transform (FILT)

The enterohepatic circulation of cefixime in rat was evaluated by a nonlinear least square analysis program, MULTI(FILT), into which the fast inverse Laplace transform (FILT) was incorporated. The plasma time course in the bile duct-cannulated rat exhibited a biexponential curve after the rapid iv administration of cefixime. Several pharmacokinetic models for the enterohepatic circulation were constructed based on the recirculatory concept and the Laplace-transformed equations corresponding to these models were derived by means of the method of transfer function. The transformed equations were simultaneously fitted to the time courses of plasma concentration in rats with laparotomy and with bile duct cannula. The optimum model was selected based on the Akaike's information criterion (AIC). The local moment characteristics for a single pass through enterohepatic circulation were further calculated from the time courses of both the plasma concentration and the amount excreted into the bile. The recovery ratio (F_c and the mean circulatory time (¯t_c through a single pass of enterohepatic circulation were estimated 27.9% and 1.07 hr, respectively. The recovery ratio (F_a and the mean absorption time (¯t_a for the absorption process from the intestinal tract into the systemic circulation were 68.3% and 0.0234 hr, respectively. The recovery ratio (F_b and the mean transit time (¯t_b)for the disposition process through the systemic circulation into the bile were 40.8% and 1.05hr, respectively.Notation A _i coefficient - a _i exponent - (s) Laplace transform of the time course of plasma following intravenous dose - (s) Laplace transform of the time course of plasma following oral administration dose - (s) Laplace transform of the time course of plasma concentration without EHC - CL_b clearance into the bile - CL¹ total clearance through the single EHC (=CL_b/F_b) - D_iv intravenous dose - D_po oral administration dose - F_a recovery (availability) from intestinal tract to systemic circulation - F_b recovery from systemic circulation to intestinal tract - F_a recovery from oral dose (absolute availability) - F_c recovery through a single pass of EHC - F_g recovery through the stomach - (s) transfer function corresponding to the process outside the body through the intestinal tract - (s) transfer function for oral dose - (s) transfer function through the systemic circulation into the bile - (s) transfer function for a single pass of EHC - (s) transfer function through the stomach - f_i(t) weight function for the processi - (s) Laplace transform off _t (t) - (s) transfer function corresponding to the recirculatory process - k_a absorption rate constant - s Laplace variable - mean transit time for the absorption process from the intestinal tract - _a mean transit time for oral dose (=MAT) - mean transit time for the disposition process in the body - mean transit time for a single pass of EHC - t ₀ gap time