With the development of insulin resistance (IR), there is a compensatory increase in the plasma insulin response to offset the defect in insulin action to maintain normal glucose tolerance. The insulin response is the result of two factors: insulin secretion and metabolic clearance rate of insulin (MCRI). Subjects (104 with normal glucose tolerance [NGT], 57 with impaired glucose tolerance [IGT], and 207 with type 2 diabetes mellitus [T2DM]), divided in nonobese and obese groups, received a euglycemic insulin-clamp (40 mU/m2 ⋅ min) and an oral glucose tolerance test (OGTT) (75 g) on separate days. MCRI was calculated during the insulin-clamp performed with [3-3H]glucose and the OGTT and related to IR: peripheral (glucose uptake during the insulin clamp), hepatic (basal endogenous glucose production × fasting plasma insulin [FPI]), and adipocyte (fasting free fatty acid × FPI). MCRI during the insulin clamp was reduced in obese versus nonobese NGT (0.60 ± 0.03 vs. 0.73 ± 0.02 L/min ⋅ m2, P < 0.001), in nonobese IGT (0.62 ± 0.02, P < 0.004), and in nonobese T2DM (0.68 ± 0.02, P < 0.03). The MCRI during the insulin clamp was strongly and inversely correlated with IR (r = −0.52, P < 0.0001). During the OGTT, the MCRI was suppressed within 15–30 min in NGT and IGT subjects and remained suppressed. In contrast, suppression was minimal in T2DM. In conclusion, the development of IR in obese subjects is associated with a decline in MCRI that represents a compensatory response to maintain normal glucose tolerance but is impaired in individuals with T2DM. 相似文献
This study aimed to determine the seroprevalence and determinants of hepatitis B virus (HBV) infection among university students in Bangladesh. This cross-sectional study was conducted among 614 students from five universities in central Bangladesh. Data were collected on demographic information, immunization history, medical and blood transfusion history through the face-to-face interview. Blood samples were collected and screened for anti-HBsAg using ELISA, HBsAg Rapid Test-cassette, and immune chromatographic test. The overall seroprevalence of HBV infection was 5.0%, and vaccination coverage was 19.2% among the participants. Students having a history of surgery (OR 11.004, 95% CI 3.211–37.707), blood transfusion (OR 5.651, 95% CI 0.965–33.068), being married (OR 4.776, 95% CI 1.508–15.127), and not being vaccinated (OR 9.825, 95% CI 1.130–85.367) were at higher risk of being infected by HBV. This study showed the endemicity of HBV infection among the Bangladeshi population. Marriage, surgical or blood transfusion history, not being vaccinated were the determinants of HBV infection within the study population. Public health initiatives for preventing HBV infection at the university levels should be envisaged.
IntroductionPolio, which is caused by poliovirus, is a contagious, potentially crippling, and deadly disease. Pakistan is one of the countries in which polio is still endemic in the 21st century. In 2019, 146 polio cases were reported across the country with some resulting in deaths. Following the spread of rumors insinuating that children were falling sick after receiving an anti-polio vaccine, a mob attacked and set fire to a small hospital in the Peshawar district in April 2019. The present study investigates readers’ discussions that emerged from Dawn’s online readers’ comments on polio-related news stories in Pakistan.MethodsUsing thematic analysis, we analyzed (N = 2216) comments made by readers in the polio-related news stories published on Dawn.com from January 1, 2012, to March 1, 2020.ResultsSeven major themes emerged from the analysis of the comments: 1) reasons for and challenges resulting in the failure to eradicate polio; 2) proposed solutions and policy changes to eradicate polio; 3) misinformation; 4) criticism, frustration, and shame; 5) comparison of Pakistan to other countries; 6) the internet as a public sphere; 7) suffering, empathy, and appreciation. Overall, our findings suggested that commenters are knowledgeable about polio vaccines and consider polio a serious threat to public health in Pakistan.ConclusionOur study not only validated previous study findings such as reasons, challenges, and issues related to polio vaccination, but also found new challenges in online news sites concerning misinformation on polio and polio vaccination in Pakistan. 相似文献
This paper highlights a series of studies using the male rhesus monkey that has led to a model for the control of the onset of puberty in higher primates. The model proposes that the timing of puberty in these species is governed by the duration of a central brake that, during juvenile development, holds in check the hypothalamic network of gonadotropin-releasing hormone (GnRH) neurons, which, in the adult, drive the pituitary-gonadal axis. The neurobiology of this hypothalamic brake, and the physiological mechanisms that time its application and removal, are incompletely understood. Nevertheless, the pubertal resurgence of pulsatile GnRH release, which terminates the juvenile phase of primate development and triggers the initiation of puberty in man and monkeys, is associated with structural and molecular remodeling of the hypothalamus. A major component of this developmental plasticity appears to involve neuropeptide Y (NPY). NPY inhibits GnRH release, and NPY gene expression in the hypothalamus is elevated during juvenile development when GnRH release is restrained. Since the changes in hypothalamic function and morphology that trigger primate puberty unfold in the absence of gonadal steroid feedback, the possibility is raised that, in addition to activating the pituitary-gonadal axis at this stage of development, they may also contribute directly to the causation of behaviors and affective states that emerge at adolescence. 相似文献
To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4+ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4+ T-cell recall responses. Therapeutically, CD4+ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4+ T cells with CaEno1 modulated host CD4+ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4+ T-cell responses. 相似文献
Fourty patients with univentricular heart, underwent a cavopulmonary shunt procedure. The majority have an excellent hemodynamic status with ventricular end diastolic pressure > 12 mmHg and a mean pulmonary artery pressure > 15 mmHg. However, 11 patients have ventricular dysfunction, 9 have an incompetent systemic atrio-ventricular valve and 6 have mean pulmonary artery pressure > 15 mmHg. The pulmonary arteries were of a good size in all cases with a Nakata index > 100 mm2/m2. Cavopulmonary connections are satisfactory palliative procedures in the treatment of univentricular cardiac disease. 相似文献
Effects of different concentrations of tetrakis--3,5-diisopropylsalicylatodiaquodicopper(II) (Cu(II)2(3,5-DIPS)4(H2O)2) on the reduced status of glutathione (GSH), the major nonprotein thiol in tissues, were investigated using freshly isolated hepatocytes. Cu(II)2(3,5-DIPS)4 below 100 M did not have any significant effects on either the GSH content or viability of the hepatocytes, but at 150–250 M it decreased both parameters after 1 h of incubation. The decrease in cellular GSH was not followed by an increase in the oxidized form of GSH (GSSG) in the cell suspension. The addition of deferoxamine with Cu(II)2(3,5-DIPS)4 to the hepatocyte suspension prevented depletion in GSH content and loss of cell viability by Cu(II)2(3,5-DIPS)4. Both GSH depletion and loss of cell viability were found to be Cu(II)2(3,5-DIPS)4 dose dependent. From these results, it appears that Cu(II)2(3,5-DIPS)4 penetrated the cell membrane and acted by decreasing the GSH level by forming a copper-glutathione complex. 相似文献
Three commercially available brands of amikacin were investigated in a parallel study design for the assessment of comparative pharmacokinetics in pediatric oncology patients with chemotherapy-induced neutropenic febrile episode. Amikacin concentration in serum samples was determined by fluorescence polarization immunoassay method using Abbott TDx system. Computer software, PK II was used for computation of pharmacokinetic parameters of amikacin. The serum concentration of all brands nonsignificantly (p > 0.05) varied at all time points, except at 1 and 2 hrs post dosing. At 1 hr post dosing, the serum concentration of brand II varied from rest of two brands. Whereas at 2 hr following I/V infusion, brands II and I were statistically different. Highest serum concentration of 38.69 +/- 1.45 microg/ml was observed in case of brand III while brands I and II showed lower but not significantly different serum concentration values, i.e., 36.30 +/- 1.65 and 37.89 +/- 1.32 microg/ml, respectively when compared with brand I. The other pharmacokinetic parameters of 3 brands found to have non-significant difference (P < 0.05) except, t(1/2)alpha and Cl of brands I and II that deviated statistically significant (p < 0.01). The relative bioavailability of brand II and III as compared with brand I, considered as standard 86.17 and 96.86%, respectively falls within the accepted limits of +/- 20% required for the bioequivalence of any two brands. Based upon findings of the present study, all these brands may be used interchangeably in oncology patients. Further studies, however are needed to determine whether the statistically elevated Cl value in brand II is of any clinical significance. 相似文献