Obesity and Metabolic Phenotypes (Metabolically Healthy and Unhealthy Variants) Are Significantly Associated with Prevalence of Elevated C-Reactive Protein and Hepatic Steatosis in a Large Healthy Brazilian Population

Background. Among the obese, the so-called metabolically healthy obese (MHO) phenotype is thought to confer a lower CVD risk as compared to obesity with typical associated metabolic changes.The present study aims to determine the relationship of different subtypes of obesity with inflammatory-cardiometabolic abnormalities. Methods. We evaluated 5,519 healthy, Brazilian subjects (43 ± 10 years, 78% males), free of known cardiovascular disease. Those with \u3c2 metabolic risk factors (MRF) were considered metabolically healthy, and thosewith BMI ≥ 25 kg/m2 and/or waist circumference meetingNCEP criteria for metabolic syndrome as overweight/obese (OW). High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and hepatic steatosis (HS) was determined via abdominal ultrasound. Results. Overall, 40% of OWindividuals were metabolically healthy, and 12% normal-weight had ≥2 MRF.The prevalence of elevated CRP (≥3mg/dL) and HS inMHO versus normal weight metabolically healthy group was 22% versus 12%, and 40%versus 8%respectively ( \u3c 0.001). BothMHOindividuals andmetabolically unhealthy normal weight (MUNW) phenotypes were associated with elevated hsCRP and HS. Conclusion. Our study suggests that MHO and MUNW phenotypes may not be benign and physicians should strive to treat individuals in these subgroups to reverse these conditions

Cigarette smoking worsens systemic inflammation in persons with metabolic syndrome

Background Emerging data suggests that the combination of smoking and metabolic syndrome (MetS) markedly increases cardiovascular disease risk well beyond that of either condition. In this study we assess if this interaction can be explained by an additive increase in the risk of systemic inflammation by MetS and cigarette smoking. Methods We evaluated 5,503 healthy non-diabetic Brazilian subjects (mean age of 43 ± 10 years, 79% males). Participants were divided into sub-groups of smokers and non-smokers with or without MetS. High-sensitivity C reactive protein (hs-CRP) was measured to assess degree of underlying inflammation. Results Overall (19%) had hs-CRP \u3e 3 mg/L. In adjusted regression analyses, compared to non-smokers, there was a 0.19 mg/L (95% CI: 0.05, 0.32) increase in hs-CRP among smokers in the entire population and 0.63 mg/L (95% CI: 0.26, 1.01) increase among smokers with MetS while there was no significant increase among smokers without MetS (β = 0.09 95% CI: -0.05, 0.24). In a fully adjusted logistic regression model, smokers compared to non-smokers were 55% more likely to have elevated hs-CRP in the entire population (OR 1.55, 95% CI: 1.25, 1.92) and more than twice as likely to have elevated hs-CRP if they had MetS ( OR 2.05, 95% CI: 1.40, 3.01) while the risk was non-significant among those without MetS (OR = 1.29, 95% CI: 0.98, 1.69). Conclusion The study demonstrates an additive effect of cigarette smoking on the risk of systemic inflammation in MetS thus highlighting the need for determining smoking status among those with MetS and aggressively targeting smoking cessation in this population

How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property

The modern concept of ‘dynasty’ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegel’s references to ‘dynasty’, read with Marx’s critique, further show how ‘dynasty’ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about ‘dynasty’ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of ‘dynasty’ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/‘tribal’ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ‘rajavamshi’ and ‘Kshatriya’. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe

Attenuating effects of prior oestradiol benzoate priming on 5-HT-mediated lordosis behavior in rats are dose-dependent

The present study was designed to investigate the role of the 5-HT7 receptors in lordosis and compare the lordotic responses with 5-HT1A agent under the influence of different steroid-priming regimens in ovariectomized, non-receptive and receptive rats. 8-OH DPAT, a 5-HT1A agonist and 5-CT, a 5-HT7 agonist inhibited the lordosis differently in non-receptive and receptive rats, however, the response was attenuated in a dose-dependent manner following 5-CT treatment in the first two tests. Treatment with 5-HT1A antagonist, WAY 100 135 caused a protective effect which was evident in the second test only. Priming with 25 μg OB attenuated in the first test in non-receptive rats whereas the same dose repeated a similar pattern in receptive rats. The attenuation of LQ was evident in rats treated with 5-HT7 antagonist, SB 269970-A.This finding shows that WAY 100 135, a 5-HT1A antagonist has potency to attenuate inhibitory influence of 8-OH DPAT by enhancing lordosis behavior acutely in female rats with a low estrous state. Treatment with 5-CT and SB 269970-A as 5-HT7 agonist and antagonist, respectively, have mimicked 5-HT-mediated lordotic response as moderate affinity towards 5-HT1A receptors has been reported. This offers a comparable effect on lordosis as a result of the two 5-HT agents used

Morphine induces reproductive changes in female rats and their male offspring

The effect of intrauterine morphine exposure on the development of reproductive functions has been investigated in the rat. Female rats were treated daily ip with morphine sulfate, doses increasing at 10-d intervals from 5, 7.5, 10, to 15 mg/kg. These rats were mated between day 38 and 45, and morphine treatment continued at 20 and 30 mg/kg over pregnancy and at up to 40 mg/kg for 10 d postpartum. The treatment mainly disrupted ovarian cyclicity; only 48% exhibited normal cyclicity. Of these, 43% became pregnant when mature male rats were placed with them. Litter size was normal but with significantly more stillbirths in each litter and live pups had decreased body weights. Male offspring had reduced body weight at the time of weaning that persisted until 60 d of age. At 120 d, animals showed complete abolition of spermatogenesis and drastically reduced testicular steroidogenesis. Plasma LH levels were low, and hypothalamic noradrenaline was high

Application of quasi-emulsification and modified double emulsification techniques for formulation of tacrolimus microsponges

Muhammad Zaman,1 Sundus Qureshi,1 Kishwar Sultana,1 Muhammad Hanif,2 Asif Mahmood,1 Zaib Ali Shaheryar,1 Faisal Gulzar,1 Kashif Barkat,1 Mohamed M Abdel-Daim3 1Faculty of Pharmacy, University of Lahore, Lahore, Pakistan; 2Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan; 3Department of Pharmacology, Suez Canal University, Ismailia, Egypt Background: The present study was to develop a stable and sustained-release delivery system of tacrolimus (TCM). TCM is a macrolide antibiotic used as an immunosuppressant. It is formulated as a microsponge, which is a safe and effective delivery system with reduced side effects.Materials and methods: The method used to prepare ethyl cellulose (EC) and xanthan gum (XG)-facilitated EC-based microsponges employed emulsification and modified double emulsification techniques. TCM-containing microsponges were prepared using varying concentrations followed by evaluation of micromeritics, compatibility of drug and excipients, production yield, drug content and entrapment efficiency, zeta potential, size distribution and drug release.Results: The results showed excellent flow properties with adequate entrapment efficiency of the system and satisfactory release of active pharmaceutical ingredient. In vitro dissolution studies, which were conducted to determine the amount of drug released, illustrated a pronounced sustained effect up to 8 h. Zeta size and zeta potential analysis of microsponges confirmed the existence of micro-sized (1.99–3.09 µm) and stable particles (-15.33 to -3.38 mV), respectively.Conclusion: Conclusively, the applied technique and selected combination of ingredients were found suitable for the preparation of TCM-containing sustained-release microsponges. Keywords: ethylcellulose, xanthan gum, macrolides, tacrolimus, sustained releas