Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles of the pertussis toxin genes, constructed by replacing either one or two key amino acids within the enzymatically active S1 subunit, were introduced into the chromosome of strains of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. These strains produce mutant pertussis toxin molecules that are nontoxic and immunogenic and that protect mice from the intracerebral challenge with virulent Bordetella pertussis. Such molecules are ideal for the development of new and safer vaccines against whooping cough.
Context: Low-T 3 syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T 3 replacement therapy in patients with low-T 3 syndrome and ischemic or nonischemic dilated cardiomyopathy (DC).Design: A total of 20 clinically stable patients with ischemic (n ϭ 12) or nonischemic (n ϭ 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66 -77; median, 25-75th percentile) who underwent 3-d synthetic L-T 3 infusion (study group); the other 10 patients (average age 68 yr, range 64 -71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T 3 (initial dose: 20 g/m 2 body surface⅐d) or placebo infusion.Results: After T 3 administration, free T 3 concentrations increased until reaching a plateau at 24 -48 h (3.43, 3.20 -3.84 vs. 1.74, 1.62-1.93 pg/ml; P ϭ 0.03) without side effects. Heart rate decreased significantly after T 3 infusion (63, 60 -66 vs. 69, 60 -76 beats per minute; P ϭ 0.008). Plasma noradrenaline (347; 270 -740 vs. 717, 413-808 pg/ml; P ϭ 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P ϭ 0.02), and aldosterone (175, 152-229 vs. 231, 154 -324 pg/ml; P ϭ 0.047) significantly decreased after T 3 administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T 3 administration, left-ventricular end-diastolic volume (142, 132-161 vs. 133, 114 -158 ml/m 2 body surface; P ϭ 0.02) and stroke volume (40, 34 -44 vs. 35, 28 -39 ml/m 2 body surface; P ϭ 0.01) increased, whereas external and intracardiac workload did not change. Conclusions:In DC patients, short-term synthetic L-T 3 replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T 3 administration. (J Clin Endocrinol
The prevalence of overweight, obesity, and their related complications is increasing worldwide. The purpose of this umbrella review was to summarize and critically evaluate the effects of different diets on anthropometric parameters and cardiometabolic risk factors. Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, and Web of Science, from inception to April 2019, were used as data sources to select meta-analyses of randomized controlled trials that examined the effects of different diets on anthropometric parameters and cardiometabolic risk factors. Strength and validity of the evidence were assessed through a set of predefined criteria. Eighty articles reporting 495 unique meta-analyses were examined, covering a wide range of popular diets: low-carbohydrate (n = 21 articles), high-protein (n = 8), low-fat (n = 9), paleolithic (n = 2), low-glycemic-index/load (n = 12), intermittent energy restriction (n = 6), Mediterranean (n = 11), Nordic (n = 2), vegetarian (n = 9), Dietary Approaches to Stop Hypertension (DASH) (n = 6), and portfolio dietary pattern (n = 1). Great variability in terms of definition of the intervention and control diets was observed. The methodological quality of most articles (n = 65; 81%), evaluated using the “A MeaSurement Tool to Assess systematic Reviews-2” questionnaire, was low or critically low. The strength of evidence was generally weak. The most consistent evidence was reported for the Mediterranean diet, with suggestive evidence of an improvement in weight, BMI, total cholesterol, glucose, and blood pressure. Suggestive evidence of an improvement in weight and blood pressure was also reported for the DASH diet. Low-carbohydrate, high-protein, low-fat, and low-glycemic-index/load diets showed suggestive and/or weak evidence of a reduction in weight and BMI, but contrasting evidence for lipid, glycemic, and blood pressure parameters, suggesting potential risks of unfavorable effects. Evidence for paleolithic, intermittent energy restriction, Nordic, vegetarian, and portfolio dietary patterns was graded as weak. Among all the diets evaluated, the Mediterranean diet had the strongest and most consistent evidence of a beneficial effect on both anthropometric parameters and cardiometabolic risk factors. This review protocol was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42019126103.
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