Acceptability and uptake of HPV vaccine in Argentina before its inclusion in the immunization program: a population-based survey

In Argentina, human papillomavirus (HPV) vaccination was approved in 2006, but not included in the National Immunization Program. In 2008 a mass media campaign was carried out by a cancer Non-Governmental Organization (NGO), but it was stopped due to criticisms about the publicity. In October 2011 the Ministry of Health (MoH) has introduced HPV vaccination in the National Immunization Program. In this context, to assure high HPV vaccine coverage, evidence is needed on factors both associated to vaccine acceptability and uptake. In 2009-2010 we carried out a population-based survey among a representative sample of 1200 women aged 18-49 years from the Metropolitan Area of Buenos Aires. The objective was twofold: first to analyze socio-demographic determinants of women's knowledge on HPV vaccine and secondly, determinants of actual HPV vaccine uptake and acceptability in Argentina after the above-mentioned vaccine advertising shown in mass media in the year 2008. We analyzed vaccine uptake/acceptability separately for women and for their daughters aged 9-15, and willingness to vaccinate one's daughter younger than 9 to receive future HPV vaccination. Results of the 1200 women interviewed, 438 women (36.5%) knew the HPV vaccine and 303 (25%) remembered the mass media advertisement about HPV vaccination. When asked whether she would get vaccinated after having seen/heard the advertisement, around 75% (n=226) of women answered surely/probably yes. No significant differences in socio-demographic characteristics were found among women who would or not get vaccinated. When surveyed, 6 women had been vaccinated. Main reasons for non-vaccination were: "Doctor did not mention/recommend it" (34.1%) and "Vaccine is too expensive" (15.7%). No woman had had their 9-15 year-old daughter vaccinated. Among women who only had at least one daughter under 9 (n=278), 74% answered that they would get their daughter vaccinated if they were pre-adolescents. The conclusion is that, in Argentina, the potential acceptability of the vaccine is high, given that there is acceptance among the professional community, physicians recommend it, and vaccine is affordable.     

Default mode network in concussed individuals in response to the YMCA physical stress test

We hypothesize that the evolution of mild traumatic brain injury (mTBI) may be related to differential effects of a concussive blow on the functional integrity of the brain default mode network (DMN) at rest and/or in response to physical stress. Accordingly, in this resting-state functional magnetic resonance imaging (fMRI) study, we examined 14 subjects 10±2 days post-sports-related mTBI and 15 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the DMN is disrupted at the resting state and/or following the physical stress test. First, all mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. Second, the functional integrity within the DMN, a main resting-state network, remained resilient to a single concussive blow. Specifically, the major regions of interest (ROIs) constituting the DMN (e.g., the posterior cingulate cortex [PCC]/precuneus area, the medial prefrontal cortex [MPFC], and left and right lateral parietal cortices [LLP and RLP]) and the connectivity within these four ROIs was similar between NVs and mTBI subjects prior to the YMCA physical stress test. However, the YMCA physical stress test disrupted the DMN, significantly reducing the magnitude of the connection between the PCC and left lateral parietal ROI, and PCC and right lateral parietal ROI, as well as between the PCC and MPFC in mTBI subjects. Thus while the DMN remained resilient to a single mTBI without exertion at 10 days post-injury, it was altered in response to limited physical stress. This may explain some clinical features of mTBI and provide some insight into its mechanism. This important finding should be considered by clinical practitioners when making decisions regarding return-to-play and clearing mTBI athletes for sports participation.     

Glipentide and glucose metabolism in isolated rat hepatocytes

Glipentide, a second generation sulfonylurea, raised the cellular concentration of fructose 2,6-bisphosphate in isolated rat hepatocytes. Parallel to accumulating this regulatory metabolite, glipentide inhibited basal gluconeogenesis and increased the rate of L-lactate production, as well as the metabolic flux through the 6-phosphofructo 1-kinase reaction. Tolbutamide elicited similar metabolic effects to those reported for glipentide, although the latter sulfonylurea was about 10 times more potent. The biochemical mechanism by which sulfonylureas promote the accumulation of fructose 2,6-bisphosphate in hepatocytes seems to be related to a significant increase of the hexose 6-phosphate pool (glucose 6-phosphate plus fructose 6-phosphate), together with the activation of 6-phosphofructo 2-kinase and inactivation of fructose 2,6-bisphosphatase, enzyme activities responsible, respectively, for the synthesis and degradation of fructose 2,6-bisphosphate.     

Catabolic effects of gastric bypass in a diet-induced obese rat model

PURPOSE OF REVIEW: In the USA, 8-10 million people are morbidly obese, which is associated with a high frequency of comorbidities. The most effective treatment is surgery. Of around 180,000 bariatric operations performed in 2005, 80% were Roux-en-Y gastric bypass, consisting of a small gastric pouch to minimize food intake and a Roux-en-Y of distal small bowel bypassing the upper gastrointestinal tract. The precise mechanisms whereby Roux-en-Y gastric bypass achieves sustained weight loss remain unknown. To gain insight into the catabolic events of sustained weight loss we developed a diet-induced obese Roux-en-Y gastric bypass rat model. We review our rat model data from the novel viewpoint of the catabolic state, comparing it with the limited human data available and the catabolic events occurring in cancer anorexia/cachexia syndrome. RECENT FINDINGS: Current data suggest the involvement of mechanisms other than restrictive and malabsorptive factors of the Roux-en-Y gastric bypass, classically thought of as the mechanisms responsible for weight loss. Based on available data, gastrointestinal hormones and cytokines play a key role in reducing food intake and regulating energy homeostasis. Because of the cross talk between peripheral modulators and the hypothalamus, a critical role for their interaction in the outcome of Roux-en-Y gastric bypass is emerging. SUMMARY: In our Roux-en-Y gastric bypass rat model many of the changes in gastrointestinal hormones, adipokines and cytokines as well as in hypothalamic neuropeptides and neurotransmitters resemble the changes observed in the anorexia/cachexia rat model, suggesting that Roux-en-Y gastric bypass triggers a catabolic state responsible for loss of appetite and prolonged body weight reduction.     

Methoxychlor induces atresia of antral follicles in ERalpha-overexpressing mice.

Methoxychlor (MXC) is a pesticide that is known to bind to estrogen receptor alpha (ERalpha) and to induce atresia of antral ovarian follicles. Although studies have shown that MXC is toxic to the ovary, we hypothesize that perturbation to the estrogen-signaling system (i.e., increase or decrease in estrogen sensitivity) might alter ovarian responsiveness to MXC. Thus, we examined whether ERalpha overexpression alters the ability of MXC to increase follicle atresia. To do so, we employed a transgenic mouse model in which ERalpha can be inducibly overexpressed in animal tissues (ERalpha overexpressors). We dosed female controls and ERalpha overexpressors with sesame oil (vehicle control) or MXC (32 and 64 mg/kg/day) for 20 days. After dosing, the ovaries were collected for histological evaluation of follicle numbers and follicle atresia, while blood was collected for measurements of hormones. Estrous cycles were determined in all animals to ensure that all were terminated during estrus. Although there were no significant effects of MXC on the numbers of primordial, primary, and preantral follicles in both controls and ERalpha overexpressors, there was an effect on antral follicles. Specifically, our data indicate that 32 and 64 mg/kg MXC increased the percentage of atretic follicles compared to vehicle in both control and ERalpha overexpressor groups. Moreover, there was a clear trend toward greater sensitivity to 64 mg/kg MXC in ERalpha-overexpressing mice compared to control animals. Specifically, at the 64-mg/kg MXC dose, ERalpha-overexpressing mice had a significantly higher percentage of atretic follicles compared to control animals (controls = 21.5 +/- 3%, n = 5; ERalpha overexpressors = 37 +/- 23%, n = 9, p < or = 0.05 vs. controls). After 20 days of dosing, there were no differences in estradiol levels between controls and ERalpha-overexpressing mice in all treatment groups. Follicle-stimulating hormone (FSH) levels were similar in sesame oil-treated control mice and control mice treated with 32 mg/kg MXC, while control mice treated with 64 mg/kg MXC had significantly lower levels of FSH compared to sesame oil-treated controls (sesame oil = 4.31 +/- 0.7, MXC [64 mg/kg/day] = 1.89 +/- 0.4, n = 3, p < or = 0.02 vs. sesame oil). ERalpha-overexpressing mice treated with sesame oil, 32 or 64 mg/kg MXC, had similar FSH levels. Thus, we observed an increased percentage of atretic antral follicles in ERalpha-overexpressing mice treated with MXC compared to control mice treated with the same compound, suggesting that the ERalpha-signaling pathway plays an important role in MXC-induced atresia. The trend toward greater sensitivity to MXC in ERalpha-overexpressing mice compared to control animals cannot be explained by alterations in estradiol and/or FSH levels.     

Investigational treatments for Type 2 diabetes mellitus: exenatide and liraglutide

Although a number of compounds are currently used to treat Type 2 diabetes mellitus, achieving a sustained glycaemic control over time is often not possible using oral antidiabetics. Endogenous incretins exhibit beneficial effects that could be useful for Type 2 diabetes mellitus treatment, such as stimulating insulin secretion during hyperglycaemia, improving beta-cell mass and function, reducing glucagon secretion, delaying gastric emptying, reducing postprandial hyperglycaemia and diminishing body weight; however, their short half-life makes them unsuitable for treatment. Incretin mimetics such as liraglutide and exenatide were developed to overcome this limitation. This review discusses the effects of these compounds and their potential as a new class of antidiabetic agents.     

In vitro tracheal hyperresponsiveness to muscarinic receptor stimulation by carbachol in a rat model of bleomycin-induced pulmonary fibrosis

1 Bleomycin-induced lung injury is widely used as an experimental model to investigate the pathophysiology of pulmonary fibrosis but the alterations in the pharmacological responsiveness of airways isolated from bleomycin-exposed animals has been scarcely investigated. The aim of this study was to examine the in vitro tracheal responses to muscarinic receptor stimulation with carbachol in a rat bleomycin model. 2 Concentration-response curves to carbachol (10 nm to 0.1 mm) were obtained in tracheal rings isolated from Sprague-Dawley rats 14 days after endotracheal bleomycin or saline. The intracellular calcium signal in response to carbachol (10 microm) was measured by epifluorescence microscopy using fura-2 in primary cultures of tracheal smooth muscle cells from bleomycin- and saline-exposed rats. Circulating plasma tumour necrosis factor (TNF)-alpha/interleukin (IL)-1beta levels were measured by enzyme-linked immunosorbent assay. 3 Maximal contraction in response to carbachol was significantly greater in tracheal rings from bleomycin-exposed rats compared with controls (15.8 +/- 1.3 mN vs. 11.8 +/- 1.4 mN; n = 19, P < 0.05). 4 Carbachol (10 microm) elicited a transient increase of intracellular calcium with greater increment in tracheal smooth muscle cells from bleomycin-exposed rats compared with controls (372 +/- 42 nmvs. 176 +/- 20 nm; n = 7, P < 0.01). 5 Circulating plasma levels of TNF-alpha/IL-1beta were augmented in bleomycin-exposed rats compared with controls. Tissue incubation with TNF-alpha (100 ng ml(-1))/IL-1beta (10 ng ml(-1)) increased in vitro tracheal responsiveness to carbachol. 6 In conclusion, tracheal contraction in response to muscarinic receptor stimulation with carbachol was increased in bleomycin-exposed rats. This in vitro cholinergic hyperresponsiveness may be related to the augmented levels of inflammatory cytokines in bleomycin-exposed rats.