Aging and mitochondria

Aging is a complex physiological phenomenon and several different theories have been elaborated about its origin. Among such theories, the 'mitochondrial theory of aging', which has gained a large support, indicates the accumulation of somatic mutations of mitochondrial DNA leading to the decline of mitochondrial functionality as one of the driving forces for the process itself. In this review data on rat and man from our laboratory and from recent literature have been thoroughly examined and compared in order to provide the 'state-of-the-art' on the role of mitochondria in aging. Alterations of structure and expression of mitochondrial genome with aging, to find out the eventual relevant changes of mitochondrial biogenesis, have been studied in rat whereas the relationship between cytochrome c oxidase activity and 'common deletion' has been studied in man. Results on the effect of acetyl-L-carnitine on the mitochondrial functionality are also reported.     

Hyperhydration: tolerance and cardiovascular effects during uncompensable exercise-heat stress

This study examined the efficacy of glycerol and water hyperhydration (1 h before exercise) on tolerance and cardiovascular strain during uncompensable exercise-heat stress. The approach was to determine whether 1-h preexercise hyperhydration (29.1 ml H2O/kg lean body mass with or without 1.2 g/kg lean body mass of glycerol) provided a physiological advantage over euhydration. Eight heat-acclimated men completed three trials (control euhydration before exercise, and glycerol and water hyperhydrations) consisting of treadmill exercise-heat stress (ratio of evaporative heat loss required to maximal capacity of climate = 416). During exercise ( approximately 55% maximal O2 uptake), there was no difference between glycerol and water hyperhydration methods for increasing (P < 0.05) total body water. Glycerol hyperhydration endurance time (33. 8 +/- 3.0 min) was longer (P < 0.05) than for control (29.5 +/- 3.5 min), but was not different (P > 0.05) from that of water hyperhydration (31.3 +/- 3.1 min). Hyperhydration did not alter (P > 0.05) core temperature, whole body sweating rate, cardiac output, blood pressure, total peripheral resistance, or core temperature tolerance. Exhaustion from heat strain occurred at similar core and skin temperatures and heart rates in each trial. Symptoms at exhaustion included syncope and ataxia, fatigue, dyspnea, and muscle cramps (n = 11, 10, 2, and 1 cases, respectively). We conclude that 1-h preexercise glycerol hyperhydration provides no meaningful physiological advantage over water hyperhydration and that hyperhydration per se only provides the advantage (over euhydration) of delaying hypohydration during uncompensble exercise-heat stress.     

Socioeconomic development, status of women, family planning, and fertility in Bangladesh: a district level analysis

In this paper we examine the effects of socioeconomic development, the status of women, and family planning on fertility and the extent to which these effects vary among the nineteen districts of Bangladesh. The 1983 and 1991 Bangladesh Contraceptive Prevalence Survey data are used to examine the effects of these factors on differences in contraceptive use among currently married women aged 15-49. The proportion of currently married women aged 15-49 using contraception was 46.3 per cent in 1991, a considerable increase from 26.5 per cent in 1983. Contraceptive use rates for all the districts increased substantially over the period between 1983 and 1991 and the gap between Dhaka's rate and those of other districts was narrower in 1991 than in 1983. An analytical model composed of socioeconomic development, status of women, and family planning variables is tested using logistic regression. The logit model is used to evaluate the effects of a selected group of variables on the probability of using contraceptive methods. The analysis demonstrates clearly that socioeconomic development and women's status significantly impact the use of contraceptive methods in Bangladesh. The results also suggest that better-educated, employed women are more likely to use contraception than those who have little or no formal education and who are not employed. In 1983, rural-urban differences in contraceptive use were significant, but in 1991 area of residence was not significant, which suggests that family planning programs may have played an important role in providing contraceptive information and technology to rural areas. Our analysis also suggests that family planning programs operated more efficiently in some districts than in others, and regional differences remained important in 1991 as they were in 1983. Decomposition analysis suggests that shifts in population structure favored increased contraceptive use in Bangladesh. This analysis also indicates that change in rate is also important, contributing about 21 per cent of the overall increase in contraceptive use.     

The GnRH system of seasonal breeders: anatomy and plasticity

Seasonal breeders, such as sheep and hamsters, by virtue of their annual cycles of reproduction, represent valuable models for the study of plasticity in the adult mammalian neuroendocrine brain. A major factor responsible for the occurrence of seasonal reproductive transitions is a striking change in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the inhibitory effects of gonadal steroids. However, the neural circuitry mediating these seasonal changes is still relatively unexplored. In this article, we review recent findings that have begun to define that circuitry and its plasticity in a well-studied seasonal breeder, the ewe. Tract tracing studies and immunocytochemical analyses using Fos and FRAs as markers of activation point to a subset of neuroendocrine GnRH neurons in the MBH as potential mediators of pulsatile GnRH secretion. Because the vast majority of GnRH neurons lack estrogen receptors, seasonal changes in responsiveness to estradiol are most probably conveyed by afferents. Two possible mediators of this influence are dopaminergic cells in the A14/A15 cell groups of the hypothalamus, and estrogen receptor-containing cells in the arcuate nucleus that project to the median eminence. The importance of GnRH afferents in the regulation of season breeding is underscored by observations of seasonal changes in the density of synaptic inputs onto GnRH neurons. Thyroid hormones may participate in this remodeling, because they are important in seasonal reproduction, influence the morphology of other brain systems, and thyroid hormone receptors are expressed within GnRH neurons. Finally, in the hamster, neonatal hypothyroidism affects the number of caudally placed GnRH neurons in the adult brain, suggesting that thyroid hormones may influence development of the GnRH system as well as its reproductive functions in the adult brain.     

A 21st century computerized injection system for local pain control

This article describes a new computerized local anesthetic injection system for pain control. The core technology of this system is the microprocessor-controlled delivery of anesthetic solution at a constant pressure and controlled volume, regardless of encountered variations in tissue resistance. This fine-tuned, high suffusion flow rate of anesthetic provides a rapid onset of anesthesia for most patients. Traditional block injections and infiltrations as well as palatal injections and periodontal ligament injections are administered with precision, ease, and patient comfort.     

Subunit structure and function of porcine factor Xa-activated factor VIII

Factor Xa and thrombin (factor IIa) activate factor VIII (fVIII) by different proteolytic pathways. Thrombin cleaves fVIII at Arg372 between the A1 and A2 domains, at Arg740 between the A2 and B domains, and at Arg1689 between the B and A3 domains to form an A1/A2/A3-C1-C2 heterotrimer. We now report a stable porcine fVIIIaXa preparation obtained by Mono S HPLC at pH 6. NH2-terminal sequence analysis of purified subunits of fVIIIaXa revealed that factor Xa cleaves fVIII at Arg219 within the A1 domain and at Arg490 within the A2 domain, as well as at Arg372, Arg740, and Arg1689. Analytical ultracentrifugation of the fVIIIaXa preparation yielded results consistent with a single, 148 kDa species, similar to previous results with fVIIIaIIa [Lollar, P., & Parker, C. G. (1989) Biochemistry 28, 666-674]. Thus, the major species in the fVIIIaXa preparation contains five subunits, including fragments of the A1 and A2 domains that remain noncovalently bound. Fluorescence anisotropy measurements indicated there was no difference in the affinity of fVIIIaXa and fVIIIaIIa for a fluorescent dye-labeled, active-site-blocked derivative of porcine factor IXa. Additionally, the fVIIIaXa preparation bound dye-labeled factor IXa with 1:1 stoichiometry, indicating that all fVIIIaXa molecules in the preparation can bind factor IXa. However, fVIIIaXa had 4-fold less procoagulant activity than fVIIIaIIa. Kinetic analysis of fVIIIa cofactor activity using purified factor IXa and factor X suggested this difference is due to greater activity of fVIIIaIIa relative to fVIIIaXa within the intrinsic fXase complex, rather than a difference in their stabilities.     

Compliance with cardiovascular disease prevention strategies: a review of the research

The efficacy of cardiovascular risk-reduction programs has been established. However, the extent to which risk-reduction interventions are effective may depend on adherence. Non-compliance, or non-adherence, may occur with any of the recommended or prescribed regimens and may vary across the treatment course. Compliance problems, whether occurring early or late in the treatment course, are clinically significant, as adherence is one mediator of the clinical outcome. This article, which is based on a review of the empirical literature of the past 20 years, addresses compliance across four regimens of cardiovascular risk reduction: pharmacological therapy, exercise, nutrition, and smoking cessation. The criteria for inclusion of a study in this review were: (a) focus on cardiovascular disease risk reduction; (b) report of a quantitative measure of compliance behavior; and (c) use of a randomized controlled design. Forty-six studies meeting these criteria were identified. A variety of self-report, objective, and electronic measurement methods were used across these studies. The interventions employed diverse combinations of cognitive, educational, and behavioral strategies to improve compliance in an array of settings. The strategies demonstrated to be successful in improving compliance included behavioral skill training, self-monitoring, telephone/mail contact, self-efficacy enhancement, and external cognitive aids. A series of tables summarize the intervention strategies, compliance measures, and findings, as well as the interventions demonstrated to be successful. This review reflects the progress made over two decades in compliance measurement and research and, further, advances made in the application of behavioral strategies to the promotion of cardiovascular risk reduction.     

Responses of preterm infants to unimodal and multimodal sensory intervention

PURPOSE: To examine the immediate responses of preterm infants to two forms of unimodal [auditory only (A) and tactile only (T)] and two forms of multimodal sensory stimulation [auditory, tactile and visual (ATV); auditory, tactile, visual and vestibular (ATVV)]. METHOD: A convenience sample of 54 clinically stable preterm infants (33-34 postconceptional weeks) was randomly assigned to 1 of 5 experimental groups [Control (C); (A); (T); (ATV); and (ATVV)]. Stimulation was applied for 15 minutes once daily for 4 consecutive days. RESULTS: Outcome measures included pulse (PR) and respiratory rate (RR), oxygen saturation, behavioral state (BS), and body temperature. Repeated measures ANOVA identified significant differences among the groups during intervention for PR (p < .001), RR (p = .01), and BS (p < .02). Infants receiving any intervention with a tactile component showed increasing arousal (change in BS), and increased PR and RR during stimulation. Group T infants had higher proportions of PR > 180 while Group ATVV had higher proportions of PR < 140 (p = .0001). Group ATVV showed increased alertness following stimulation (24%) in contrast to having the least alertness during stimulation (11%). CONCLUSIONS: Tactile stimulation alone may be too arousing for these infants while the addition of vestibular stimulation may modulate arousal and facilitate optimal arousal prior to feeding.