Physiological Makeup Research Articles

Treating Diet-Induced Obesity: A New Role for Vagal Afferents?

As of the 2007–2008 National Health and Nutrition Examination Survey, 34% of adults—or over 72 million people—were obese, having a BMI [ 30. With childhood obesity catching up, this epidemic will only continue to grow for the foreseeable future. The current ‘‘obesogenic’’ environment characteristic of developed countries is often cited as the major cause of the obesity epidemic. Nevertheless, the observation that a large percentage of the population has not become obese could imply the contribution of a gene-environment interaction. For instance, the differential response to the obesogenic environment suggests one’s inherited physiological makeup (which itself is modulated by environment) either resists or favors obesity. Being obese might not be so unfortunate if weight gain and increased fat mass were the only consequences. Nonetheless, obesity is associated with numerous consequences such as diabetes, cardiovascular disease, and cancer [1], which in turn are related to proportionately large visceral abdominal fat stores [2]. Regrettably, no satisfactory non-invasive treatment for obesity has been developed. As a consequence, increasing numbers of expensive and risky bariatric surgical procedures, the only effective current therapies, are performed. Gastric bypass, though reasonably effective at reducing body weight, has been useful for treating type 2 diabetes [3]. The mechanism underlying these effects is not fully understood, but appears to involve decreases in consumption of high calorie foods, reductions of meal size and nutrient absorption, changes of anorexigenic and orexigenic hormone levels, increased energy expenditure, and altered vagal gastrointestinal (GI) innervation [4]. The key to the success of bypass in reducing body weight may thus be due to its effects on multiple organ systems. Before bariatric procedures became popular, truncal vagotomy, involving division of the right and left vagal trunks below the diaphragm was employed to treat morbid obesity [5]. Nonetheless, the interruption of vagal premotor axons as part of the vagotomy procedure caused gastric stasis and ‘‘dumping’’ of food from the stomach to the intestine, causing unpleasant sensations, including nausea. One way to overcome the adverse side effects of vagotomy and retain some of the benefits was to reduce or avoid damage to the vagal pre-motor axons. Indeed, selective sensory vagotomy may retain some of the benefits as it reduces food intake, body weight, and fat accumulation in rodent obesity models [6, 7]. Moreover, sensory vagotomy reduced the excess abdominal visceral fat found in aging rats [7]. Stearns et al. [8] took this approach further by distinguishing the effects of sensory vagotomy on different fat depots in rats subjected to diet-induced obesity (DIO). Sensory vagotomy was achieved by applying capsaicin to the abdominal vagal branches, and comparing the effect of this treatment on DIO in rats fed a high-energy ‘‘Western diet’’ for 11 months with the effects of truncal vagotomy and sham surgery. Interestingly, although sensory vagotomy non-significantly reduced body weight, it also modestly, but significantly and selectively, reduced visceral abdominal fat by 18% compared with controls. This is an important finding given the aforementioned association of central obesity with several causes of morbidity and mortality and since small changes in the size of the visceral fat depot can exert sizeable influences on overall mortality risk [9]. Stearns et al. [8] further suggested that sensory vagotomy could provide a valuable E. A. Fox (&) Behavioral Neurogenetics Laboratory, Ingestive Behavior Research Center, Department of Psychological Sciences, Purdue University, 703 Third Street, West Lafayette, IN 47907, USA e-mail: au_gc@psych.purdue.edu

Evaluating acoustic speaker normalization algorithms: Evidence from longitudinal child data

Speaker vowel formant normalization, a technique that controls for variation introduced by physical differences between speakers, is necessary in variationist studies to compare speakers of different ages, genders, and physiological makeup in order to understand non-physiological variation patterns within populations. Many algorithms have been established to reduce variation introduced into vocalic data from physiological sources. The lack of real-time studies tracking the effectiveness of these normalization algorithms from childhood through adolescence inhibits exploration of child participation in vowel shifts. This analysis compares normalization techniques applied to data collected from ten African American children across five time points. Linear regressions compare the reduction in variation attributable to age and gender for each speaker for the vowels BEET, BAT, BOT, BUT, and BOAR. A normalization technique is successful if it maintains variation attributable to a reference sociolinguistic variable, while reducing variation attributable to age. Results indicate that normalization techniques which rely on both a measure of central tendency and range of the vowel space perform best at reducing variation attributable to age, although some variation attributable to age persists after normalization for some sections of the vowel space.

The power–duration relationship of high‐intensity exercise: from mathematical parameters to physiological mechanisms

The power–duration relationship of high‐intensity exercise: from mathematical parameters to physiological mechanisms

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Flip-flop pharmacokinetics is a phenomenon often encountered with extravascularly administered drugs. Occurrence of flip-flop spans preclinical to human studies. The purpose of this article is to analyze both the pharmacokinetic interpretation errors and opportunities underlying the presence of flip-flop pharmacokinetics during drug development. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters. When flip-flop is expected or discovered, a longer duration of sampling may be necessary in order to avoid overestimation of fraction of dose absorbed. Common culprits of flip-flop disposition are modified dosage formulations; however, formulation characteristics such as the drug chemical entities themselves or the incorporated excipients can also cause the phenomenon. Yet another contributing factor is the physiological makeup of the extravascular site of administration. In this article, these causes of flip-flop pharmacokinetics are discussed with incorporation of relevant examples and the implications for drug development outlined.

Enrolment and Retention of African Women in Biomedical Research: the Challenges

In Africa, women have had minimal participation in biomedical research especially in clinical trials despite the epidemiologic realities of the trends and burden of diseases in the continent. The purpose of this paper is to critically examine the challenges as well as suggesting ways of over-coming them in recruiting and retaining African women in biomedical research. Relevant biomedical research literatures on Human Research Participants from Scirus, Pubmed and Medline computerized search were critically evaluated and highlighted Information was also obtained from research ethics training as well as texts and journals in the medical libraries of the research ethics departments of the Universities of Pretoria, Kwazulu-Natal, Johns Hopkins Berman Institute of Bioethics Baltimore and Kennedy Institute of Bioethics Georgetown University, Washington DC. Studies reviewed have shown that African women have an unfair participation in biomedical research. Efforts in enrolling and retaining women in biomedical research are hampered by chain reactions of events viz: gender perception, cultural barriers, ignorance and fear of adverse event, limited autonomy to give consent, lack of confidentiality especially in sensitive trials, and improper research design. Women need to participate in clinical trials because of their different biological and physiological make-up which require proper information about the effects of drugs on their bodies. A variety of harm may therefore ensue from failure to include adequate numbers of women in biomedical research such as exposure to ineffective treatment, occurrence of unexpected side-effects and delayed diagnosis and early treatment of disease.

Multiple Peaking Phenomena in Pharmacokinetic Disposition

Multiple peaking in the blood fluid concentration-time curve is a phenomenon occasionally encountered in pharmacokinetics. When it occurs, it can create difficulties in the determination and interpretation of pharmacokinetic parameters. Multiple peaking can occur as a consequence of a number of different mechanisms. These include, in addition to others, factors related to the formulation, be it the drug chemical entity itself or other formulation-related factors such as the excipients incorporated into the product design. Another contributing factor that can work in concert with the formulation is the physiological makeup of the gastrointestinal tract itself. This includes the pH and components of bile such as bile salts and phospholipids, the secretion of which is regulated by hormonal and dietary factors. In some cases, biochemical differences in the regional areas of the gastrointestinal tract, such as regio-specificity in bile concentrations and/or transport proteins, could contribute to windows for absorption that result in multiple peaking of xenobiotics. One of the most common sources of multiple peaking is contributed by biliary secretion followed by intestinal reabsorption of a drug, a process for which the term 'enterohepatic recycling' has been coined. This cause of multiple peaking is associated with special consideration in the calculation and interpretation of the drug clearance and volume of distribution. In this review, each of these various causes of multiple peaking is discussed, with incorporation of relevant examples for illustrative purposes.

Survey of Caffeine Intake from Children's Favorite Foods

The daily caffeine intake from elementary school children’s favorite foods was surveyed and evaluated. Children may respond to caffeine differently from adults because they have different physiological makeup and are functionally immature. Therefore, caffeine exposure may have more serious consequences for children than for adults, irrespective of sensitivity. Their preference, perception, and intake of caffeine from children’s favorite foods were investigated by questionnaire for 355 children. The order of children’s preference over foods containing caffeine was ice cream and ices, confectionary, milk and milk products, and soft beverage. The daily caffeine intake of children was estimated to range from 0.16 to 917.28 ㎎/day, with an average of 36.04 ± 82.7 ㎎/day and 36.9 ± 96.0 ㎎/day for boys and girls, respectively. The daily caffeine intake according to body weight was 1.08 ± 2.23 ㎎/㎏ and 1.12 ± 2.66 ㎎/㎏ for boys and girls, respectively. The percentage of acceptable daily intake (ADI) of caffeine was 43.4% for boys and 44.9% for girls. The sources of caffeine for boys and girls were soft beverage (18.3 ㎎ and 16.1 ㎎), milk and milk products (8.9 ㎎ and 8.5 ㎎), ice cream and ices (5.7 ㎎ and 7.3 ㎎), chocolate (1.6 ㎎ and 3.2 ㎎), and confectionery (1.6 ㎎ and 1.8 ㎎).

128 N-METHYL-D-ASPARTIC ACID CAN BE USED TO PARTIALLY REPLACE BOVINE SERUM ALBUMIN IN CULTURE MEDIUM

One major obstacle in mammalian embryo culture has been unidentifiable biological contaminants in the media due to the inclusion of Bovine Serum Albumin (BSA) or Fetal Bovine Serum. The goal of this study was to remove BSA from culture media and develop chemically defined media based off the embryo’s biological and physiologic makeup. We evaluated the presence of message in various stages of porcine embryos and found that the message for the ionic glutamate receptor, N-Methyl-D-aspartic acid (NMDA) increased about 3-fold from oocyte to blastocyst. Thus, this study was conducted to determine if the addition of NMDA (0.5 mm) would improve development of embryos in an already chemically defined medium. Slaughterhouse derived ovaries were aspirated, cumulus–oocyte complexes were identified and then matured for 42 h in M199 base medium supplemented with EGF, FSH, and LH. Metaphase II oocytes were selected and fertilized in modified Tris buffered medium with 0.25 × 106 mL–1 frozen–thawed porcine semen for 5 h. Presumptive zygotes were then transferred to Porcine Zygote Medium with 0.3% BSA (PZM3) or 0.1% PVA (PZM4). After 28 h, cleaved embryos were selected and embryos were placed into treatment groups: (1) PZM3, (2) PZM4, or (3) PZM4 + 0.5 mm NMDA. Embryos were cultured in 5% CO2, 5%O2, 90% N2 until Day 7. For this experiment the number of cleaved embryos cultured in each treatment group were 260 for group 1, 220 for group 2 and 300 for group 3. Percentage of development to blastocyst was determined and analyzed with SAS Proc GENMOD Procedure (a,b P < 0.05). The percentage developed to blastocyst was (1) 47.5% a, (2) 29.6% b, and (3) 36.1% a,b, respectively. Total cell number of the blastocysts was determined by using Hoechst nuclear stain and statistically analyzed by SAS Proc GENMOD Procedure. The average cell number for the treatment groups was (1) 25.8 a, (2) 19.6 b, and (3) 22.9 a,b, respectively. Culture without BSA significantly reduced development to blastocyst and total cell number; however, with the addition of 0.5 mm NMDA there was no significant difference from media containing BSA. This indicates that NMDA can be used to partially replace BSA to form a chemically defined media. Funded by a grant from the USDA NRI 2006-35203-17282.

Personalized medicine: impact of subject matter and utility requirements on patentability in the United States

Personalized medicine is a relatively new field that recognizes and takes advantage of a patient's individual genetic and physiologic make-up, as well as specific environmental influences. Obtaining and defending patents this field, however, can raise legal issues, such as those relating to ‘subject matter’ patentability and ‘utility,’ two requirements under US law. This perspective article provides an analysis of certain US patent cases relevant to these requirements, including Lab. Corp. v. Metabolite pertaining to subject matter patentability of certain types of diagnostic methods, and In re Fisher addressing the utility of certain DNA-related research tools. Understanding such cases can provide guidance as to how to avoid certain pitfalls when preparing, prosecuting and defending patents in the field of personalized medicine.

Wine grape (Vitis vinifera L.) color associates with allelic variation in the domestication gene VvmybA1

During the process of crop domestication and early selection, numerous changes occur in the genetic and physiological make-up of crop plants. In grapevine (Vitis vinifera) numerous changes have occurred as a result of human selection, including the emergence of hermaphroditism and greatly increased variation in berry color. This report examines the effect of human selection on variable skin color by examining the variation present in the gene VvmybA1, a transcriptional regulator of anthocyanin biosynthesis. In over 200 accessions of V. vinifera, the insertion of the retroelement Gret1 in the promoter region of VvmybA1 was in strong association with the white-fruited phenotype. This retroelement was inserted at the same location for each individual in which it was present. Additional polymorphisms in the VvmybA1 gene were also strongly associated with red or pink fruited accessions, including variation that was generated by the excision of Gret1 from the promoter of VvmybA1. Differences in nucleotide diversity were observed between the white and pigmented alleles of VvmybA1, suggesting that the white allele arose only once or a limited number of times. Rarely, association of Gret1 with the white fruited phenotype was not observed, suggesting that the white phenotype can also be obtained through mutation in additional genes. These results provide evidence that variation in one transcriptional regulator has generated an allelic series strongly associated with fruit color variation in cultivated grapevine. These findings provide information about the evolution of grapes since domestication and have direct implications for the regulation of fruit and wine quality of this important crop plant.

Remaking the real man: Erectile dysfunction palliatives and the social re-construction of the male Heterosexual life cycle

The popularity of impotence or erectile dysfunction (ED) drugs and the powerful imagery of their promotional campaigns may be a significant contributor to the social reconstruction of male sexuality and aging in general, and popular understandings of the male heterosexual in particular. This is note-worthy given that the heterosexual male is a demographic that has, historically, been quite resistant to the whims of the psycho-medical establishment. Given men’s psychological and physiological makeup, the emerging social expectations of male sexuality may be wholly unrealistic, with its matter-overmind rhetoric. Examining the language and imagery of several ED drug campaigns, and considering some popular therapeutic, and academic discourse on the subject, the paper considers some of the expectations facing men in our society today that have recently been generated by the sexual pharmacology industry. The analysis suggests how these new expectations potentially liberate and constrain men in various ways, solidifies a male ethos that focuses almost exclusively on the physical component, and thereby displaces men from the context of the romantic relationship.

Vitamin nutrition of livestock animals: Overview from vitamin discovery to today

The term “vitamin” or “vitamine” was first used in 1912. What later became known as vitamin deficiency diseases — scurvy, beriberi, night blindness and xeropthalmia — had plagued the world from antiquity. From 1900 through the 1930s, experiments with animals helped to advance knowledge of vitamins considerably. There are 15 vitamins of significance for livestock. A number of factors influence vitamin requirements and vitamin utilization, including physiological make-up and production function; confinement rearing without pasture; stress, disease and adverse environmental conditions; vitamin antagonists; use of antimicrobial drugs; and body vitamin reserves. Under commercial livestock and poultry production conditions, vitamin allowances higher than National Research Council (USA) requirements may be needed for optimum performance. Generally, the optimum vitamin supplementation level is the quantity that achieves the best growth rate, feed utilization and health (including immune competency), while also providing adequate body reserves. Key words: Vitamins, history, deficiency, requirements, supplementation

Changes in Cry1Ac Bt Transgenic Cotton in Response to Two Environmental Factors: Temperature and Insect Damage

The efficacy of Cry1Ac Bacillus thuringiensis (Bt) cotton plants against field populations of Helicoverpa armigera (Hübner) has been inconsistent over the growing season. Any reduction in efficacy (where efficacy is the capacity of the plant to affect the survival of the insect) increases the opportunities for H. armigera to evolve resistance to Bt toxin. Changes in efficacy could be due to changes at the level of gene expression and/or in the physiological makeup of the plant and may be induced by environmental conditions. Two environmental factors, temperature and insect damage, were investigated. Temperature was found to affect efficacy, whether plants were grown at different temperatures continuously or were exposed to a change in temperature for a short period. Damage caused by chewing insects (H. armigera larvae) produced a dramatic increase in the efficacy of presquare Bt cotton. In contrast, damage by sucking insects (aphids) did not induce changes in efficacy. Changes in efficacy seemed to be mediated through modification of the physiological background of the plant rather than changes in the level of Cry1Ac expression or in the concentration of the Bt toxin. The impact of the non-Bt responses of plants on strains of H. armigera should be evaluated. It is possible that by enhancing existing defensive mechanisms of plants, the rate of evolution of resistance to Bt toxins could be retarded by increasing the plants overall toxicity through the additive effects of the toxins and plant defenses.

Sex and Racial Differences in Pharmacological Response: Effect of Route of Administration and Drug Delivery System on Pharmacokinetics

Mechanistic investigations into the physiological and biochemical differences between patients have only recently begun to help explain what was previously categorized as "intersubject variability." Additional factors, including the particular drug formulation or delivery system, have been implicated in observed sex-based and race-based differences in pharmacokinetic response. Drug absorption following intramuscular injection can be highly variable if the injection is mistakenly placed in the overlying tissues, a situation that is more likely to occur in women than men. Slower gastric emptying in women can significantly delay the onset of effectiveness of enteric-coated dosage forms, and differences in gastric pH can affect the drug solubility and dissolution rate. Slower drug release rates designed into many extended release dosage forms interact with the differential locations and populations of intestinal and hepatic transporters and metabolizing enzymes to cause significant sex-based and race-based differences in plasma drug concentrations. Increased efforts to identify and understand the interplay of an individual's physiological makeup, dietary intake, environment, and the drug products he or she uses are needed to be able to provide optimal drug therapy regimens to each patient.

Updates on the treatment of epilepsy in women.

Epilepsy is a condition of the central nervous system that is characterized by recurrent seizures. The goal of management is to make patients seizure free without intolerable adverse effects from treatment. Men and women differ in their physiologic makeup and therefore have different needs that must be considered when attempting to attain this goal. There are special concerns for women of child-bearing years with regard to contraception, pregnancy, and teratogenicity that should be considered during counseling and selection of appropriate treatment. There are also emerging concerns about the interaction of antiepileptic drugs and endocrine function that can affect ovarian function, induce polycystic ovary (PCO)-like syndrome, and threaten fertility. Systemic adverse effects can have a negative impact on weight, cosmetic appearance, sexual function, and bone health. Individualized treatment coupling antiepileptic drug use and the specific phase of impact of the reproductive cycle must be considered in treatment selection. Important concerns regarding long-term therapy are being raised as there are more treatment options to consider because of the plethora of new antiepileptic drugs that are available, often with more favorable pharmacokinetics and different adverse event profiles. Also, sex hormone fluctuations during maturation may exacerbate seizures at particular points during the life cycle for women, including menarche, during menses, during pregnancy, or later in the perimenopausal years, often presenting a uniquely challenging aspect to treatment. As the number of available treatment options for epilepsy increases, the optimal goal for primary care physicians is to work as a team with obstetricians, gynecologists, and neurologists in an effort to ensure the best treatment of women with epilepsy.

Management of cerebral perfusion pressure after traumatic brain injury.

IN 1996, the Brain Trauma Foundation sponsored the development of guidelines for the management of severe traumatic brain injury (TBI). The method used for development of the guidelines was evidence based, and probably the most significant contribution of the guidelines has been to highlight the remarkable lack of class I evidence available for many current management practices. Recently, revisions to the guidelines were published, and little has been changed in the recommendations. 1 From all of the aspects of management that were reviewed for the guidelines, the authors were only able to provide three standards based on class I evidence (randomized clinical trials) and only eight guidelines based on class II evidence (table 1). Furthermore, the randomized clinical trials that have supported the three guideline standards showed ineffectiveness of certain long-standing management practices (prophylactic hyperventilation, steroid administration, prophylactic anticonvulsants) rather than showing that any practices are

Head and neck resonance in a rhesus monkey - a comparison with results from a human model

The use of primates for examining the effects of electromagnetic radiation on behavioural patterns is well established. Rats have also been used for this purpose. However, the monkey is of greater interest as its physiological make-up is somewhat closer to that of the human. Since the behavioural effects are likely to occur at lower field strengths for resonant absorption conditions for the head and neck, the need for determination of resonance frequencies for this region is obvious. Numerical techniques are ideal for the prediction of coupling to each of the organs, and accurate anatomically based models can be used to pinpoint the conditions for maximum absorption in the head in order to focus the experiments. In this paper we use two models, one of a human male and the other of a rhesus monkey, and find the mass-averaged power absorption spectra for both. The frequencies at which highest absorption (i.e. resonance) occurs in both the whole body and the head and neck region are determined. The results from these two models are compared for both E-polarization and k-polarization, and are shown to obey basic electromagnetic scaling principles.

Overtraining in Athletes

Overtraining appears to be caused by too much high intensity training and/or too little regeneration (recovery) time often combined with other training and nontraining stressors. There are a multitude of symptoms of overtraining, the expression of which vary depending upon the athlete's physical and physiological makeup, type of exercise undertaken and other factors. The aetiology of overtraining may therefore be different in different people suggesting the need to be aware of a wide variety of parameters as markers of overtraining. At present there is no one single diagnostic test that can define overtraining. The recognition of overtraining requires the identification of stress indicators which do not return to baseline following a period of regeneration. Possible indicators include an imbalance of the neuroendocrine system, suppression of the immune system, indicators of muscle damage, depressed muscle glycogen reserves, deteriorating aerobic, ventilatory and cardiac efficiency, a depressed psychological profile, and poor performance in sport specific tests, e.g. time trials. Screening for changes in parameters indicative of overtraining needs to be a routine component of the training programme and must be incorporated into the programme in such a way that the short term fatigue associated with overload training is not confused with the chronic fatigue characteristic of overtraining. An in-depth knowledge of periodisation of training theory may be necessary to promote optimal performance improvements, prevent overtraining, and develop a system for incorporating a screening system into the training programme. Screening for overtraining and performance improvements must occur at the culmination of regeneration periods.

Calcium-channel blockers in prophylaxis and treatment of asthma

Calcium-channel blocking drugs do not induce bronchoconstriction in susceptible persons with cardiac disease and concomitant hyperreactive airways (such as asthma or chronic bronchitis). The ways in which calcium blockers might in fact play a beneficial role in preventing bronchoconstriction or inducing bronchodilation in asthma are explored. Nifedipine and verapamil have been shown to inhibit the bronchoconstriction provoked by exercise, histamine, methacholine and antigen. The potential mechanisms by which this protective effect is mediated—whether by direct action on tracheobronchial smooth muscle, inhibition of release of mediators from activated mast cells or both—are examined by reviewing in vitro studies of both cell systems. Calcium blockers also exhibit some bronchodilating activity in vitro. Early clinical trials of these drugs in ambulatory asthmatic patients have shown little, if any, therapeutic benefit, but results must be considered preliminary in view of the nature of the short-term, small-scale trials performed to date. Regardless of their therapeutic potential in obstructive lung diseases, the calcium-channel blockers offer a powerful probe into the role of calcium in the physiologic make-up of airways and, in particular, the pathophysiologic features of airway hyperreactivity.

Afferent C-fibres: physiological and biochemical correlations

Immunocytochemistry has uncovered many populations of biochemically discrete neurons throughout the central and peripheral nervous systems. It seemed reasonable to assume that particular biochemical types of neuron would also share morphological and physiological properties, yet the evidence for this is still far from compelling. In the case of primary afferent fibres there are at least four major subgroups of unmyelinated sensory fibres, defined by their cytoplasmic content of various enzymes or peptides, and as many if not more types of receptive field profile. However, to date no direct correlation between physiological and biochemical subtypes has been made. Here we review the evidence for heterogeneity in the biochemical and physiological make-up of C-fibres and attempt to make some correlations.