Chronic Kidney Disease-associated Lung Injury Is Mediated by Phosphate-induced MAPK/AKT Signaling.

Chronic kidney disease (CKD) is associated with systemic phosphate elevations, called hyperphosphatemia. Translational studies have shown that hyperphosphatemia contributes to CKD-associated inflammation and injury in various tissues, including the kidney, heart, liver, and parathyroid gland. Mechanisms underlying pathologic actions of elevated phosphate on cells are not well understood but seem to involve uptake of phosphate through sodium phosphate cotransporters and phosphate-induced signaling via FGFR1 (fibroblast growth factor receptor 1).

FGF receptors mediate cellular senescence in the cystic fibrosis airway epithelium.

The number of adults living with cystic fibrosis (CF) has already increased significantly because of drastic improvements in life expectancy attributable to advances in treatment, including the development of highly effective modulator therapy. Chronic airway inflammation in CF contributes to morbidity and mortality, and aging processes like inflammaging and cell senescence influence CF pathology. Our results show that single-cell RNA sequencing data, human primary bronchial epithelial cells from non-CF and CF donors, a CF bronchial epithelial cell line, and Cftr-knockout (Cftr-/-) rats all demonstrated increased cell senescence markers in the CF bronchial epithelium.

Fibroblast Growth Factor 23 Signaling Does Not Increase Inflammation from Infection in the Cystic Fibrosis Bronchial Epithelium.

: Chronic inflammation due to (PA) infection in people with cystic fibrosis (CF) remains a concerning issue in the wake of modulator therapy initiation. Given the perpetuating cycle of colonization, infection, chronic inflammation, and recurrent injury to the lung, there are increases in the risk for mortality in the CF population. We have previously shown that fibroblast growth factor (FGF) 23 can exaggerate transforming growth factor (TGF) beta-mediated bronchial inflammation in CF.

A novel in vitro model to study prolonged Pseudomonas aeruginosa infection in the cystic fibrosis bronchial epithelium.

Pseudomonas aeruginosa (PA) is known to chronically infect airways of people with cystic fibrosis (CF) by early adulthood. PA infections can lead to increased airway inflammation and lung tissue damage, ultimately contributing to decreased lung function and quality of life. Existing models of PA infection in vitro commonly utilize 1-6-hour time courses.

Phosphate induces inflammation and exacerbates injury from cigarette smoke in the bronchial epithelium.

An elevation in serum phosphate-also called hyperphosphatemia-is associated with reduced kidney function in chronic kidney disease (CKD). Reports show CKD patients are more likely to develop lung disease and have poorer kidney function that positively correlates with pulmonary obstruction. However, the underlying mechanisms are not well understood.

Cystic Fibrosis Lung Disease in the Aging Population.

The demographics of the population with cystic fibrosis (CF) is continuously changing, with nowadays adults outnumbering children and a median predicted survival of over 40 years. This leads to the challenge of treating an aging CF population, while previous research has largely focused on pediatric and adolescent patients. Chronic inflammation is not only a hallmark of CF lung disease, but also of the aging process.

Behavior therapy for obsessive-compulsive disorder guided by a computer or by a clinician compared with relaxation as a control.

Background: The demand for effective behavior therapy for obsessive-compulsive disorder (OCD) by exposure and ritual prevention exceeds its supply by trained therapists. A computer-guided behavior therapy self-help system (BT STEPS) was created that patients access by telephone from home via interactive voice response technology. This study compared the value of computer-guided behavior therapy value with that of clinician-guided behavior therapy and systematic relaxation as a control treatment.

Lecithin consumption increases acetylcholine concentrations in rat brain and adrenal gland.

Consumption of a single meal containing lecithin, the major source of choline occurring naturally in the diet, increased the concentrations of choline and acetylcholine in rat brain and adrenal gland. Hence, the concentration of acetylcholine in the tissues may normally be under direct, short-term nutritional control.

Oral choline administration to patients with tardive dyskinesia.

We gave pharmacologic doses of choline to patients with tardive dyskinesia in an attempt to suppress involuntary facial movements. Choline is the physiologic precursor of acetylcholine, and its administration elevates brain acetylcholine levels in laboratory animals and, possibly, in human beings. Hence, we thought that its use could benefit patients with diseases like tardive dyskinesia, which is believed to result from deficient central cholinergic tone.

Lecithin consumption raises serum-free-choline levels.

Consumption of choline by rats sequentially increases serum-choline, brain-choline, and brain-acetylcholine concentrations. In man consumption of choline increases in levels in the serum and cerebrospinal fluid; its administration is an effective way of treating tardive dyskinesia. We found that oral lecithin is considerably more effective in raising human serum-choline levels than an equivalent quantity of choline chloride.

Trans-synaptic induction of adrenomedullary tyrosine hydroxylase activity by choline: evidence that choline administration can increase cholinergic transmission.

Twenty-four hours after rats receive choline chloride (20 mmol/kg, by stomach tube) the activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.

Tryptophan concentrations in rat brain. Failure to correlate with free serum tryptophan or its ratio to the sum of other serum neutral amino acids.

Groups of rats were deprived of food overnight and then given free access to diets designed to raise (carbohydrate) or lower (carbohydrate and large neutral amino acids) brain tryptophan concentrations. Similar diets were supplemented with 40% fat and fed to other groups. All animals were killed 2h after food presentation.

Effects of skim milk, whole milk and light cream on serum tryptophan binding and brain tryptophan concentrations in rats.

One hour after rats fasted for 13 hours consume a single meal of skim milk, whole milk, or light cream, serum nonesterified fatty acid (NEFA) concentrations changed in direct proportion to the fat content of the diet: serum NEFA levels decreased in rats ingesting skim milk (0.09% fat) to 34% of fasting control values; in animals consuming whole milk (3.59% fat), levels dropped to 50% of fasting levels; these levels did not change significantly, however, in rats consuming light cream (18.