Biological Variability in Serum Cortisol Concentration Post-adrenocorticotropic Hormone Stimulation in Healthy Dogs.

BACKGROUND: The ACTH stimulation has low sensitivity for the diagnosis of hypercortisolism possibly as a result of biological and analytical variability. HYPOTHESIS/OBJECTIVES: To report the components of biological and analytical variability in serum cortisol concentration post-ACTH stimulation ([cortisol]) in healthy dogs. ANIMALS: Fourteen healthy harrier hound dogs. METHODS: The data were extracted from a separate, prospective, randomized, double-blinded, controlled discovery study in which dogs treated with vehicle control and 4 different doses of cortisone acetate (CA) for 7 days had an ACTH stimulation test performed to confirm the dose-dependent effect of CA. The index of individuality (IoI), the critical difference between sequential measurements (CD ), and the number of measurements required to assess the homeostatic set point (HSP) of [cortisol] with confidence intervals (CI) of 90 and 95% were estimated. RESULTS: The IoI was equal to 1.1 and the CD was 3.3 µg/dL (92 nmol/L). The number of measurements required to assess the HSP of [cortisol] with CI of 90 and 95% were 3 and 15, respectively. Additionally, mean [cortisol] was higher in males than in females (13.3 ± 4 µg/dL [366 ± 114 nmol/L] vs. 11.5 ± 2.5 µg/dL [318 ± 65 nmol/L], respectively; P = .046). As expected, treatment with CA resulted in a dose-dependent suppression of [cortisol]. CONCLUSIONS AND CLINICAL IMPORTANCE: False-negative test results in hypercortisolism could occur when [cortisol] is outside of the individual's HSP and within the reference interval. The large CD emphasizes the importance of assessing clinically relevant parameters in the diagnosis and monitoring of HC.

Severe hypoglycaemia and its association with psychological well-being in Australian adults with type 1 diabetes attending specialist tertiary clinics.

AIM: To investigate severe hypoglycaemia (SH) in adults with type 1 diabetes and its associations with impaired awareness of hypoglycaemia (IAH), clinical, psychological and socio-demographic factors. METHODS: Attendees of three specialist diabetes clinics in Melbourne, Australia completed questions about frequency of SH in the past six months; impaired awareness of hypoglycaemia (Gold score); and measures of general emotional well-being (WHO-5), diabetes-specific positive well-being (subscale of W-BQ28), diabetes-related distress (PAID) and fear of hypoglycaemia (HFS). RESULTS: Of 422 participants (mean ± SD age 37.5 ± 15.0 years; 54% women), 78 (18.5%) reported at least one SH event and 86 (20.5%) had IAH. SH and IAH frequencies were similar at all clinics. In total, 194 SH events were reported, with 10 people experiencing 40% of events. Compared with those without SH, participants with SH had longer diabetes duration, were younger at diabetes onset and more likely to have IAH (p<0.01). Those with SH had greater fear of hypoglycaemia and diabetes-related distress, poorer general emotional well-being, and lower diabetes-specific positive well-being, (p<0.01). There were no associations with age, gender, insulin regimen or HbA1c. CONCLUSIONS: This study has identified that SH and IAH in Australian adults with type 1 diabetes exist at similar levels to those reported in US and European research. SH was significantly associated with IAH and fear of hypoglycaemia. Assessment of hypoglycaemia, IAH and psychological well-being as part of a routine diabetes clinic visit was well accepted by attendees and enabled identification of those who may benefit from medical, educational or therapeutic interventions.

The metabolic fate of cholesterol-5 alpha, 6 alpha-expoxide in vivo.

[14C] Cholesterol-5 alpha, 6 alpha-expoxide, administered to mice by either gastric intubation or skin painting, was rapidly and primarily excreted in the feces. Residual amonts of the epoxide and its metabolites were found in a wide variety of organs, and persisted for at least 72 hr. At some sites (principally the liver, the small intestinal contents and the combined stomach/duodenum and their contents), the labeled compound existed in a water-soluble form which could not be extracted with chloroform/methanol. Treatment of the small intestinal contents with a preparation of beta-glucuronidase/sulfatase produced a marked increase in the amount of organic-solvent-extractable cholesterol-alpha-epoxide and other polar metabolites. Unchanged epoxide was found mainly in the feces and the skin at the site of application. On the basis of these results, stool specimens, and not blood samples, should be analyzed to detect the presence of this compound and/or its metabolites in vivo.

Mutagenic activity of tryptophan metabolites produced by rat intestinal microflora.

The catabolism of tryptophan by rat intestinal microflora was studied for the production of mutagenic metabolites that might be involved in the etiology of colon cancer. Various tryptophan metabolites were assayed for mutagenic and comutagenic activity in the Ames bacterial test system. These included metabolites that were identified by thin-layer chromatography in cultures of rat fecal bacteria, other compounds structurally related to tryptophan, whole unfractionated mixed fecal bacteria culture filtrates, and concentrated solvent extracts. A total of 27 materials were tested with 5 Salmonella strains in the mutagenesis assay. Most substances were inactive, and only one compound, o-aminoacetophenone, which was unlikely to be produced in the intestine, showed weak comutagenic activity. Our results did not support the hypothesis that tryptophan metabolites produced by intestinal microflora are major etiologic factors in cancer of the colon.