Primary aldosteronism is caused by bilateral idiopathic hyperplasia in approximately two-thirds of cases and aldosterone-producing adenoma in one-third. Most patients with primary aldosteronism are normokalemic. In the clinical setting of normokalemic hypertension, patients who have resistant hypertension and hypertensive patients with a family history atypical for polygenic hypertension should be tested for primary aldosteronism. The ratio of plasma aldosterone concentration to plasma renin activity has been generally accepted as a first-line case-finding test. If a patient has an increased ratio, autonomous aldosterone production must be confirmed with an aldosterone suppression test. Once primary aldosteronism is confirmed, the subtype needs to be determined to guide treatment. The initial test in subtype evaluation is CT imaging of the adrenal glands. If surgical treatment is considered, adrenal vein sampling is the most accurate method for distinguishing between unilateral and bilateral adrenal aldosterone production. Optimal treatment for aldosterone-producing adenoma or unilateral hyperplasia is unilateral laparoscopic adrenalectomy. The idiopathic bilateral hyperplasia and glucocorticoid-remediable aldosteronism subtypes should be treated pharmacologically. All patients treated pharmacologically should receive a mineralocorticoid receptor antagonist, a drug type that has been shown to block the toxic effects of aldosterone on nonepithelial tissues.

The purpose of this study was to elucidate possible relationships between the oxygen concentration of the middle ear cavity and the development of myringosclerosis. Three groups of rats with myringotomized tympanic membranes were exposed to different oxygen concentrations of 10%, 15%, and 40%, respectively, for 1 week. A fourth group was kept in ambient air. Two other groups of rats with myringotomized and intubated tympanic membranes were exposed to oxygen concentrations of 10% and 40%, respectively, for the same period of time. Otomicroscopically, all hyperoxic animals had more numerous myringosclerotic lesions compared with the ambient air group, and also displayed a pronounced hyperplasia of the keratinizing epithelium around the perforation border. By contrast, the hypoxic animals showed less pronounced myringosclerotic lesions or even completely lacked them. It is inferred that an increased oxygen concentration in the middle ear cavity will increase the likelihood of myringosclerotic deposits. The mechanism involved could be related to the formation of oxygen radicals.

The present study was designed to establish whether or not an increased production of oxygen-derived free radicals is involved in the causation of myringosclerosis. Sclerotic lesions in the tympanic membrane were experimentally elicited by keeping rats with perforated tympanic membranes in an atmosphere containing roughly 40% oxygen. The animals were treated daily with a solution containing either copper zinc-superoxide dismutase plus catalase, deferoxamine, or copper sulfate plus iron chloride, applied to the traumatized area. After 1 week the extension of myringosclerotic plaques was determined otomicroscopically. The pars tensa and pars flaccida were then dissected free and prepared for light microscopic studies. The results showed that treatment with copper zinc-superoxide dismutase plus catalase and deferoxamine inhibited or reduced the development of myringosclerosis, whereas the ears treated with copper sulfate plus iron chloride appeared unaffected. Consequently, the findings support the hypothesis that the formation of oxygen free radicals contributes significantly to the development of myringosclerosis.

Women have a higher percentage of body fat than men, and there is a gender-specific difference in fat distribution: Females tend to accumulate fat around the hips, buttocks, and thighs while men have a larger intra-abdominal (visceral) fat mass. After menopause, there is a redistribution of fat depots, and post-menopausal women develop increased amounts of visceral fat. The risk of developing obesity-related diseases is significantly lower in pre-menopausal women compared to men, a difference that is abolished after menopause, suggesting that the female sex steroid estrogen influences adipogenesis and adipose metabolism. Experimentally, estrogen increases the size and number of subcutaneous adipocytes and attenuates lipolysis. Post-menopausal women also develop a more atherogenic lipid pattern and decreased levels of the prothrombotic protein plasminogen activator inhibitor-1, which attenuates fibrinolysis. Pathologically increased circulating cortisol concentration is associated with dysmetabolic features e.g., central obesity, elevated blood pressure, insulin resistance, and dyslipidemia. In "simple obesity," glucocorticoid production is elevated. Peak levels of circulating cortisol are however low or normal, possibly because of increased clearance and/or tissue-specific changes in cortisol production. In addition to the adrenal production of cortisol, cortisol is also generated in adipose tissue by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inactive cortisone to active cortisol. The enzyme activity in subcutaneous fat increases with increasing body weight. Estrogen seems to have a tissue-specific influence on 11betaHSD1 enzyme activity, attenuating it in liver, kidney, and testis but upregulating 11betaHSD1 mRNA expression in preadipocytes from women. In the present review, we summarize and discuss the interaction between glucocorticoids and sex steroids and their influence on adipocyte metabolism.

Myringosclerosis, a common finding after myringotomy, has been recently associated with an increased production of oxygen free radicals. Ascorbic acid's proposed actions include collagen synthesis, antioxidation, and free radical scavenging. The effects of topical ascorbic acid on healing tympanic membranes were studied. Particular attention was given to detecting the presence of myringosclerosis. Twelve Sprague-Dawley rats were bilaterally myringotomized. Their ears were randomized into group A, which received topical ascorbic acid in Gelfoam, group B, which received topical saline solution in Gelfoam, and group C, which received no treatment. The tympanic membranes were harvested on day 13, after routine otomicroscopy. Under light microscopy, the connective tissue layer of the untouched side of the pars tensa was distinctly thicker in group A than in group B or group C. At this level, the extent of sclerotic lesions was significantly less in the ascorbic acid-treated group. It is inferred that topical ascorbic acid reduces the occurrence of myringosclerosis following tympanic membrane perforations in the rat.

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High-density protein microarrays of recombinant human protein fragments, representing 12,412 unique Ensembl Gene IDs, have here been produced and explored. These protein microarrays were used to analyse antibody off-target interactions, as well as for profiling the human autoantibody repertoire in plasma against the antigens represented by the protein fragments. Affinity-purified polyclonal antibodies produced within the Human Protein Atlas (HPA) were analysed on microarrays of three different sizes, ranging from 384 antigens to 21,120 antigens, for evaluation of the antibody validation criteria in the HPA. Plasma samples from secondary progressive multiple sclerosis patients were also screened in order to explore the feasibility of these arrays for broad-scale profiling of autoantibody reactivity. Furthermore, analysis on these near proteome-wide microarrays was complemented with analysis on HuProt™ Human Proteome protein microarrays. The HPA recombinant protein microarray with 21,120 antigens and the HuProt™ Human Proteome protein microarray are currently the largest protein microarray platforms available to date. The results on these arrays show that the Human Protein Atlas antibodies have few off-target interactions if the antibody validation criteria are kept stringent and demonstrate that the HPA-produced high-density recombinant protein fragment microarrays allow for a high-throughput analysis of plasma for identification of possible autoantibody targets in the context of various autoimmune conditions.

In the era towards precision medicine, we here present the individual specific autoantibody signatures of 193 healthy individuals. The self-reactive IgG signatures are stable over time in a way that each individual profile is recognized in longitudinal sampling. The IgG autoantibody reactivity towards an antigen array comprising 335 protein fragments, representing 204 human proteins with potential relevance to autoimmune disorders, was measured in longitudinal plasma samples from 193 healthy individuals. This analysis resulted in unique autoantibody barcodes for each individual that were maintained over one year's time. The reactivity profiles, or signatures, are person specific in regards to the number of reactivities and antigen specificity. Two independent data sets were consistent in that each healthy individual displayed reactivity towards 0-16 antigens, with a median of six. Subsequently, four selected individuals were profiled on in-house produced high-density protein arrays containing 23,000 protein fragments representing 14,000 unique protein coding genes. Based on a unique, broad and deep longitudinal profiling of autoantibody reactivities, our results demonstrate a unique autoreactive profile in each analyzed healthy individual. The need and interest for broad-ranged and high-resolution molecular profiling of healthy individuals is rising. We have here generated and assessed an initial perspective on the global distribution of the self-reactive IgG repertoire in healthy individuals, by investigating 193 well-characterized healthy individuals. HIGHLIGHTSA unique longitudinal profiling of autoantibody repertoires in healthy individuals Autoantibody profiles are highly individual and stable over time All individuals display IgG binding to human protein fragments The specificity of disease associated autoantigens needs to be thoroughly characterized The identification of a small set of highly reactive autoantigens Importance of stringent antigen and sample specific cut-offs for defining reactivity ARTICLE HISTORY