Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review

In order to develop efficient therapeutic regimes for chronic obstructive pulmonary disease (COPD), N-acetylcysteine (NAC) has been tested as a medication which can suppress various pathogenic processes in this disease. Besides its well-known and efficient mucolytic action, NAC meets these needs by virtue of its antioxidant and anti-inflammatory modes of action. NAC is a thiol compound which by providing sulfhydryl groups, can act both as a precursor of reduced glutathione and as a direct ROS scavenger, hence regulating the redox status in the cells. In this way it can interfere with several signaling pathways that play a role in regulating apoptosis, angiogenesis, cell growth and arrest and inflammatory response. Overall, the antioxidant effects of NAC are well documented in in vivo and in vitro studies. It successfully inhibits oxidative stress at both high and low concentrations, under acute (in vitro) and chronic administration (in vivo). With regard to its anti-inflammatory action, in contrast, the effects of NAC differ in vivo and in vitro and are highly dose-dependent. In the in vitro settings anti-inflammatory effects are seen at high but not at low concentrations. On the other hand, some long-term effectiveness is reported in several in vivo studies even at low dosages. Increasing the dose seems to improve NAC bioavailability and may also consolidate some of its effects. In this way, the effects that are observed in the clinical and in vivo studies do not always reflect the success of the in vitro experiments. Furthermore, the results obtained with healthy volunteers do not always provide incontrovertible proof of its usefulness in COPD especially when number of exacerbations and changes in lung function are chosen as the primary outcomes. Despite these considerations and in view of the present lack of effective therapies to inhibit disease progression in COPD, NAC and its derivatives, because of their multiple molecular modes of action, remain promising medication once doses and route of administration are optimized.     

Tribological Characteristics of a-C:H:Si and a-C:H:SiOx Coatings Tested in Simulated Body Fluid and Protein Environment

This paper presents the tribological properties of silicon and oxygen incorporated diamond-like carbon coatings tested in simulated body fluid and bovine serum albumin environments. The tests were performed using a ball-on-disc tribometer with an AISI316L steel counterbody. The wear tracks and wear scars were analyzed using optical microscopy and a nanoindenter. The interaction between the coating and the working environment was analyzed by Fourier transform infrared spectroscopy, whereas changes in the chemical structure before and after the tribological tests were compared with the use of Raman spectroscopy. Our study showed that the tribological parameters are governed by the presence of oxygen rather than the changing concentration of silicon. Both of the spectroscopy results confirm this statement, indicating that coatings with low concentrations of silicon and oxygen appear to be better candidates for biological applications in terms of wear resistance.     

Minireview: Endocannabinoids and gonadal hormones: bidirectional interactions in physiology and behavior

Endocannabinoids act as a major neuromodulatory system in a variety of physiological and behavioral functions. Three major lines of evidence suggest that the endocannabinoid system interacts with gonadal hormones. First, the endocannabinoid system is implicated in behaviors and physiological functions that are known to be regulated in part by gonadal hormones. Second, receptors and metabolic enzymes of the endocannabinoid system are localized extensively on structures in the hypothalamic-pituitary-gonadal axis. Third, changes in levels of gonadal hormones alter endocannabinoid signaling. Here we reviewed and summarized the current evidence regarding the interaction between the endocannabinoid system and androgens, estrogens, and progesterone. Overall, it appears that bidirectional interactions characterize the relationship between endocannabinoids and gonadal hormones, with endocannabinoids down-regulating hypothalamic-pituitary-gonadal activity and gonadal hormones modulating protein expression in the endocannabinoid system. An understanding of these interactions will have implications for elucidating the neuroendocrine mechanisms underlying a number of behavioral and physiological functions as well as potential pharmaceutical treatments for disorders of these functions.     

Contraception and abortion in Argentina: perspective of obstetricians and gynaecologists

OBJECTIVE: To explore the role of obstetricians and gynaecologists in reproductive public health policies in Argentina. MATERIAL AND METHODS: Combination of quantitative methods (survey, n=467) and qualitative methods (semistructured interview, n=35; focus groups, n=6). RESULTS: The great majority of respondents believe that abortion and contraception are serious public health issues. Seven out of 10 considered the implementation of family planning services and post-abortion contraceptive counseling to be priorities. One-half favored promoting social debate on abortion. The great majority thought that de-criminalization of abortion would help to diminish maternal mortality and that abortion should not be penalized when the womans life or health is at risk, or in cases of rape or fetal malformations. CONCLUSIONS: Abortion and contraception are important issues for physicians. Advocacy efforts within this community need to focus on an integral vision of health, emphasizing their social responsibility.     

Microalbuminuria and Hypertension in Pregnancy: Role of Aldosterone and Inflammation

Women with a history of hypertension in pregnancy are at increased risk of microalbuminuria later in life. Microalbuminuria is a marker of kidney dysfunction frequently related to an inflammatory event. Pregnancy is a dynamic process characterized by immune tolerance, angiogenesis, and hormonal regulation. Menstruation and pregnancy are associated with a physiological inflammation, which is altered in preeclampsia and probably in other hypertensive situations of pregnancy. An imbalance between pro‐oxidant factors and the ability to scavenge these factors produces oxidative stress, which has been evaluated in many cells, but leukocytes are the main source of inflammatory cytokines and experimental and clinical evidence support a possible role of aldosterone as a mediator of placental and renal damage mediated by growth factors, reactive oxygen species, and cytokines. Angiotensin‐converting enzyme inhibitors and aldosterone receptor blockers are frequently effective in reducing the risk of progression of cardiovascular and renal disease.     

Tuberculosis in Malaysia: problems and prospect of treatment and control

In the early 1940s and 1950s, tuberculosis (TB) was the number one cause of death in Malaysia. Patients with TB were admitted to the many sanatoria we had in various parts of the country and were often managed by surgical means. TB chemotherapy became available only in the late 1950s. At this time, TB was already a major cause of morbidity and mortality. Realizing its seriousness, the Malaysian government launched its National TB Control Programme (NTP) in 1961. At that time, the recommended treatment for TB was a combination of three drugs, namely, streptomycin, isoniazid and paraaminosalicylic acid (PAS) given for 2 months followed by isoniazid and PAS given for 12 months. Generally the treatment used to last for 1-2 years. The National TB Centre in Kuala Lumpur functioned as the headquarters of the NTP, and the state general hospitals with their chest clinics functioned as the state directorates. From the operational point of view, every state has a state TB directorate which is known as the State TB Managerial Team (Fig. 1). This team is responsible for the implementation of the activities of the NTP at the state and district levels. Ever since 1995, the national TB directorate has been shifted to the Public Health Division of the Ministry of Health (MOH) and is now under the Director of Disease Control (Fig. 2). The National TB Centre has now been renamed as The Institute of Respiratory Medicine. Over the years from being the number one cause of death, TB has dropped to being below number 10 (Fig. 3).