In schizophrenia,non-remitters and partial remitters to treatment with antipsychotics are qualitatively distinct classes with respect to neurocognitive deficits and neuro-immune biomarkers: results of soft independent modeling of class analogy

Around one third of schizophrenia patients are non-responders to antipsychotic therapy. The present study aimed to delineate the pathway-phenotypes of non-remitters (NRTT) and partial remitters (PRTT) to treatment with antipsychotics as defined using the Global Clinical Impression scales. We recruited 60 NRTT, 50 PRTT and 43 healthy controls and measured schizophrenia symptoms, neurocognitive tests, plasma CCL11, interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box-1 protein (HMGB1), κ- and μ-opioid receptors (KOR and MOR, respectively), endomorphin-2 (EM-2), and β-endorphin. Soft independent modeling of class analogy (SIMCA) showed that NRTT and PRTT are significantly discriminated with a cross-validated accuracy of 94.7% and are qualitatively distinct classes using symptomatome, and neuro-immune-opioid-cognitome (NIOC) features as modeling variables. Moreover, a NIOC pathway phenotype discriminated PRTT from healthy controls with an accuracy of 100% indicating that PRTT and controls are two qualitative distinct classes. Using NIOC features as discriminatory variables in SIMCA showed that all PRTT were rejected as belonging to the normal control class and authenticated as belonging to their target class. In conclusion, a non-response to treatment can best be profiled using a SIMCA model constructed using symptomatome and NIOC features. A partial response should be delineated using SIMCA by authenticating patients as controls or PRTT instead of using scale-derived cut-off values or a number of scale items being rated mild or better. The results show that PRTT is characterized by an active NIOC pathway phenotype and that both NRTT and PRTT should be treated by targeting neuro-immune and opioid pathways.

     

Water and electrolyte balance in subjects with a permanent ileostomy

Water and electrolyte balance has been studied in 39 patients with a permanent ileostomy, who had had a proctocolectomy for ulcerative colitis. The findings have been compared with those in 39 healthy subjects who were matched for age and sex. The ileostomists were found to lose excessive quantities of water and sodium in the ileostomy effluent compared with the corresponding losses in normal faeces. The mean plasma total protein and albumin concentrations were increased in the ileostomists suggesting a state of chronic dehydration. The daily urinary output of sodium was low and the output of potassium was high. The urinary pH was low. The ileostomists had raised mean concentration of aldosterone in the plasma (p less than 0.001) and it is suggested that this is responsible for the body's partial compensation for the depletion of sodium and water, including the so-called ileostomy adaptation.     

Effects of two different angiotensin II antagonists on aldosterone secretion by isolated perfused rat zona glomerulosa cells

Isolated perfused rat zona glomerulosa cells have been used to determine the specificity of the angiotensin II antagonists, [Sar1,Ala8]angiotensin II and [Sar1,Ile8]angiotensin II. Both antagonists inhibited the aldosterone response to angiotensin II but did not affect serotonin- or potassium-induced aldosterone secretion. However, in contrast to [Sar1,Ala8]angiotensin II, [Sar1,Ile8]angiotensin II inhibited the aldosterone response to ACTH. These results suggest that there are differences in the specificity of these two analogs and that studies with [Sar1,Ile8]angiotensin II and its effect on aldosterone secretion should be interpreted with caution.     

Maternal personality and reproductive ambition in women is associated with salivary testosterone levels

Previous research has linked testosterone levels with sex-specific personality traits within women. The present study investigates the relation between salivary testosterone levels and specifically maternal personality traits in healthy adult women. Twenty-seven young women completed the Bem Sex Role Inventory (BSRI). Additional questions were asked about maternal personality (importance of having children, self-rated maternal/broodiness), reproductive ambition (ideal number of children, ideal own age at first child) and career orientation (importance of having career). Higher circulating testosterone levels were associated with lower scores on measures of maternal personality and reproductive ambition. There was no relation of career orientation with testosterone. A median split on BSRI masculinity revealed high scorers had higher testosterone levels than low scorers. There was no relation of BSRI femininity with testosterone. Results suggest maternal tendencies may be partly androgen driven.     

Liquorice and glycyrrhetinic acid increase DHEA and deoxycorticosterone levels in vivo and in vitro by inhibiting adrenal SULT2A1 activity

As our understanding of the complexities of the various etiologies and complex genetic architecture of GnRH deficiency grows, so too does the need to apply newly-developed genetic tools in a way that: (a) is meaningful to individuals and their families; (b) integrates all of the phenotypic features of this syndrome into a rationale; and (c) provides up-to-date diagnostic technologies in a cost-effective algorithm of genetic testing. Genetic counseling aims to accomplish these goals through ascertainment of detailed family histories, targeted comprehensive phenotypic evaluations, informed selection of genetic testing, interpretation of genetic test results, and the provision of highly specific risk assessments and psychological support to individuals diagnosed with this reproductive condition. This chapter offers a guide to incorporating this rapidly evolving state of knowledge of the pedigree and phenotypes into the process of selecting and prioritizing genetic testing. In addition, the provision of risk assessment that accounts for nuanced genetic concepts such as variable expressivity, incomplete penetrance, and oligogenicity, all of which are emerging features of the genetics of this clinical syndrome, is considered. Beyond translating genetic information, genetic counseling should address the psychological impact of embarrassment, shame, anxiety, and guilt that are often seen among individuals with reproductive disorders.     

Hsd11b2 haploinsufficiency in mice causes salt sensitivity of blood pressure

Salt sensitivity of blood pressure is an independent risk factor for cardiovascular morbidity. Mechanistically, abnormal mineralocorticoid action and subclinical renal impairment may blunt the natriuretic response to high sodium intake, causing blood pressure to rise. 11β-Hydroxysteroid dehydrogenase type 2 (11βHSD2) controls ligand access to the mineralocorticoid receptor, and ablation of the enzyme causes severe hypertension. Polymorphisms in HSD11B2 are associated with salt sensitivity of blood pressure in normotensives. In this study, we used mice heterozygote for a null mutation in Hsd11b2 (Hsd11b2(+/-)) to define the mechanisms linking reduced enzyme activity to salt sensitivity of blood pressure. A high-sodium diet caused a rapid and sustained increase in blood pressure in Hsd11b2(+/-) mice but not in wild-type littermates. During the adaptation to high-sodium diet, heterozygotes displayed impaired sodium excretion, a transient positive sodium balance, and hypokalemia. After 21 days of high-sodium feeding, Hsd11b2(+/-) mice had an increased heart weight. Mineralocorticoid receptor antagonism partially prevented the increase in heart weight but not the increase in blood pressure. Glucocorticoid receptor antagonism prevented the rise in blood pressure. In Hsd11b2(+/-) mice, high-sodium feeding caused suppression of aldosterone and a moderate but sustained increase in corticosterone. This study demonstrates an inverse relationship among 11βHSD2 activity, heart weight, and blood pressure in a clinically important context. Reduced activity causes salt sensitivity of blood pressure, but this does not reflect illicit activation of mineralocorticoid receptors by glucocorticoids. Instead, we have identified a novel interaction among 11βHSD2, dietary salt, and circulating glucocorticoids.     

Pseudomonas aeruginosa infection in hospital: a comparison between 'infective' and 'environmental' strains.

One hundred and fifty-six infections or episodes of infection associated with Pseudomonas aeruginosa in six hospitals over 14 months were investigated. Pyocine typing and serotyping suggested that 145 distinct episodes had occurred, caused by 78 different strains. During this period 15 distinct strains were isolated from the environment at one of the hospitals; 12 of these were apparently unassociated with infection in the same ward during the period, and 4 were of types not encountered in infective processes at any hospital. There appeared to be a rather higher proportion of unclassifiable pyocine inhibition patterns among the environmental strains; in general these strains also produced smaller amounts of haemolysin. If failure to produce haemolysin in vitro is correlated with lack of virulence in vivo, this may partially explain the sporadic nature of hospital infection with Ps. aeruginosa, despite the prevalence of strains of this species in the environment.