Stress amplifies lung tissue mechanics, inflammation and oxidative stress induced by chronic inflammation

ABSTRACT Background: Mechanisms linking behavioral stress and inflammation are poorly understood, mainly in distal lung tissue. Objective: We have investigated whether the forced swim stress (FS) could modulate lung tissue mechanics, iNOS, cytokines, oxidative stress activation, eosinophilic recruitment, and remodeling in guinea pigs (GP) with chronic pulmonary inflammation. Methods: The GP were exposed to ovalbumin or saline aerosols (2×/wk/4wks, OVA, and SAL). Twenty-four hours after the 4th inhalation, the GP were submitted to the FS protocol (5×/wk/2wks, SAL-S, and OVA-S). Seventy-two hours after the 7th inhalation, lung strips were cut and tissue resistance (Rt) and elastance (Et) were obtained (at baseline and after OVA and Ach challenge). Strips were submitted to histopathological evaluation. Results: The adrenals' weight, the serum cortisol, and the catecholamines were measured. There was an increase in IL-2, IL-5, IL-13, IFN-γ, iNOS, 8-iso-PGF2α, and in %Rt and %Et after Ach challenge in the SAL-S group compared to the SAL one. The OVA-S group has had an increase in %Rt and %Et after the OVA challenge, in %Et after the Ach and in IL-4, 8-iso-PGF2α, and actin compared to the OVA. Adrenal weight and cortisol serum were increased in stressed animals compared to nonstressed ones, and the catecholamines were unaltered. Conclusion & clinical relevance: Repeated stress has increased distal lung constriction, which was associated with an increase of actin, IL-4, and 8-iso-PGF2α levels. Stress has also induced an activation of iNOS, cytokines, and oxidative stress pathways.     

Acute Renal Failure and Hypercalcemia

Hypercalcemia can result from excessive bone resorption, renal calcium retention, excessive intestinal calcium absorption, or a combination of these conditions. Hypercalcemia may also provoke acute renal failure (ARF) or hypertension, or aggravate the tubular necrosis that is frequently found in cases of ARF. The association of ARF and hypercalcemia was studied retrospectively in eight patients based in the data in their charts. Data are expressed as median and percentile (25th; 75th). Our results show that ARF associated with hypercalcemia was related with comorbidity in all cases (cancer, multiple myeloma, hyperparathyroidism, sarcoidosis, vitamin D intoxication, and leprosy). Maximum median serum creatinine levels were 3.3 mg/dL (2.7, 3.8 mg/dL) before treatment and 1.1 mg/dL (0.9, 1.3 mg/dL) after treatment. Maximum total median serum calcium was 15.9 mg/dL (13.5, 19.8 mg/dL) before treatment and 9.1 mg/dL (8.4, 9.7 mg/dL) after treatment. Maximum median ionized serum calcium was 2.1 mmol/L (1.8, 2.2 mmol/L) before treatment and 1.1 mmol/L (1.0, 1.2 mmol/L) after treatment. Different kinds of treatment induced a rapid fall in serum calcium concentration. All patients were treated with hydration and diuretics, and three patients also received calcitonin. Serum creatinine concentration always fell simultaneously with the decrease in serum calcium in all cases. All patients progressed with nonoliguric renal failure. In conclusion, in ARF, patients are frequently hypocalcemic. Usually, the presence of hypercalcemia associated with ARF is indicative of the presence of comorbidity, as observed in all eight patients studied here. There was an improvement of renal function in all cases as serum calcium levels decreased.