Analytical Method Lifecycle Management in Pharmaceutical Industry: a Review.

The adoption of Quality by Design (QbD) and Analytical Method Lifecycle Management (AMLM) concepts to ensure the quality of pharmaceutical products has been applied and proposed over the last few years. These concepts are based on knowledge gained from the application of scientific and quality risk management approaches, throughout method lifecycle to assure continuous improvement and high reliability of analytical results. The overall AMLM starts with the definition of the method's intended use through the Analytical Target Profile definition, including three stages: (1) Method Design, taking advantage of the well-known concept of QbD; (2) Method Performance Qualification; (3) Continued Method Performance Verification. This is intended to holistically align method variability with product requirements, increasing confidence in the data generated, a regulatory requirement that the pharmaceutical industry must follow. This approach views all method-related activities, such as development, validation, transfer, and routine use as a continuum and interrelated process, where knowledge and risk management are the key enablers. An increase in method robustness, cost reduction, and decreased risk failures are some of the intrinsic benefits from this lifecycle management. This approach is clearly acknowledged both by regulators and industry. The roadmap of the regulatory and industry events that mark the evolution of these concepts helps to capture the current and future expectation of the pharmaceutical framework.

The use of new technologies for nutritional education in primary schools: a pilot study.

INTRODUCTION: The aim of this study was evaluating if the presence of a humanoid robot could improve the efficacy of a game-based, nutritional education intervention. STUDY DESIGN: This was a controlled, school-based pilot intervention carried out on fourth-grade school children (8-10 years old). A total of 112 children underwent a game-based nutritional educational lesson on the importance of carbohydrates. For one group (n = 58), the lesson was carried out by a nutritional educator, the Master of Taste (MT), whereas for another group, (n = 54) the Master of Taste was supported by a humanoid robot (MT + NAO). A third group of children (n = 33) served as control not receiving any lesson. METHODS: The intervention efficacy was evaluated by questionnaires administered at the beginning and at the end of each intervention. The nutritional knowledge level was evaluated by the cultural-nutritional awareness factor (AF) score. RESULTS: A total of 290 questionnaires were analyzed. Both MT and MT + NAO interventions significantly increased nutritional knowledge. At the end of the study, children in the MT and MT + NAO group showed similar AF scores, and the AF scores of both intervention groups were significantly higher than the AF score of the control group. CONCLUSIONS: This study showed a significant increase in the nutritional knowledge of children involved in a game-based, single-lesson, educational intervention performed by a figure that has a background in food science. However, the presence of a humanoid robot to support this figure's teaching activity did not result in any significant learning improvement.

Somatostatin reduces neuropeptide Y rise induced by physical exercise.

The effect of an i. v. infusion of somatostatin (SRIH) 4.1 µg/min×90 min on the basal secretion of NPY and on the NPY response to physical exercise was studied in normal men. Basal NPY secretion was not modified by SRIH infusion, whereas the NPY response to physical exercise was significantly lower in the presence of SRIH. These data suggest the involvement of a somatostatinergic mechanism in the regulation of NPY response to physical exercise.

Systemic oxytocin administration modulates NPY response to insulin-induced hypoglycemia in man.

The present study was undertaken to establish whether oxytocin (OT) is able to modify the NPY response to insulin-induced hypoglycemia in man. At 8:00 AM of 2 different days at least 1 week apart, 10 normal men were tested with insulin (0.15 IU/kg) and with the administration of OT (infused from time -15-60 min, at a constant rate of 2 mIU/ml) or placebo. Plasma NPY concentrations rose significantly during insulin tolerance test (ITT). Oxytocin treatment significantly reduced the NPY response to hypoglycemia. The finding demonstrates for the first time in humans that the systemic administration of OT exerts an inhibitory effect on the NPY rise caused by insulin-induced hypoglycemia.

Effect of serotonergic system on AVP secretion induced by physical exercise.

The present study was undertaken in order to establish the possible involvement of serotonergic receptors in the control of physical exercise-stimulated vasopressin secretion. Twenty-one healthy men (divided in three groups of seven) underwent bicycle-ergometer tests until exhaustion: exercise control test (n=21), exercise plus ondansetron, selective 5-HT3 antagonist (n=7), exercise plus buspirone, selective 5-HT1A receptor agonist (n=7), exercise plus sumatriptan, selective 5-HT1D receptor agonist (n=7). AVP levels, physiological and biochemical variables were measured and compared during tests. Results showed that exercise-induced AVP rise did not change after the administration of buspirone and sumatriptan. In contrast, the administration of ondansetron significantly reduced physical exercise-induced AVP rise. Mean peak levels during physical exercise were 4.9 times higher than basal values in the control test and 2.6 times higher than basal values in the ondansetron plus exercise test. These data demonstrate that 5-HT3 serotonergic receptors at least partially mediate the AVP response to physical exercise. On the other hand, 5-HT1A and 5-HT1D serotonergic receptors do not appear to be involved in the control of AVP secretion during exercise.

Naloxone decreases the inhibitory effect of ethanol on the release of arginine-vasopressin induced by physical exercise in man.

To establish whether ethanol and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, six healthy men underwent six bicycle-ergometer tests until exhaustion [exercise control test; exercise plus ethanol (50 of 110 ml proof whiskey orally), exercise plus naloxone (2 mg injected plus 5 mg infused or 4 mg injected plus 10 mg infused intravenously] or exercise plus ethanol plus naloxone). Plasma AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During the control test, exercise significantly increased plasma AVP levels, with a peak value five times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was abolished by ethanol. When ethanol tests were repeated in the presence of naloxone, at both lower and higher dose, ethanol inhibition on AVP secretion was only partial, with mean peak responses 2.5 times higher than basal values. Results indicate an ethanol involvement in regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying ethanol inhibitory action, but not in mediation of the AVP response to physical exercise.

Effect of naloxone on somatostatin inhibition of arginine vasopressin response to physical exercise in normal men.

To establish whether somatostatin (SRIH) and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, eight healthy men underwent four bicycle-ergometer tests until exhaustion: exercise control test; exercise plus SRIH, naloxone or SRIH plus naloxone. Serum AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During control test exercise significantly increased serum AVP levels, with a peak value 4.1 times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was significantly reduced by SRIH (AVP peak was only 2.8 times higher than baseline). When SRIH and naloxone were given together, the exercise-induced AVP rise was comparable to that observed in the control test. Results indicate a somatostatinergic involvement in the regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying SRIH inhibitory action, but not in mediation of the AVP response to physical exercise.

Specifically designed physical exercise programs improve children's motor abilities.

Physical activity in schools is declining in many countries and inactivity in childhood has become a recognized risk factor. Data from a program of professionally guided physical exercise in primary school children were collected before and after the academic year of training. Four thousand five hundred children (6-10 years) were enrolled, and conditional and coordinative motor abilities (speed, trunk flexibility, long jumping, somersault, Harre circuit test) were measured. Anthropometric measurements were focused on body mass index (BMI), weight and height. Females never showed a significant variation of BMI, whereas males in the first and fourth grades showed significant differences. On the contrary, when considering the motor abilities studied, all the comparisons were highly significant. At the end of training, both males and females did better than at the beginning, and males were constantly faster than females. Our data, generated on a large number of children, show that professionally guided programs of physical education in the primary school lead to significant progresses in the development of conditional and coordinative abilities, without altering BMI values, thus not interfering with the balanced progression of body weight and height.