Fluid and Protein Secretion by the Submandibular Glands of Weanling Rats in Response to Cholinergic and Peptidergic Agonists at Various Doses

Fluid and protein secretion by the submandibular glands of 25-day-old rats were examined and compared in response to three cholinergic and four peptidergic sialogogues at various doses. All cholinergic and peptidergic agonists used were potent sialogogues for the submandibular glands of the weanling rats over the wide range of doses used. The cholinergic agonists, bethanechol and methacholine and the peptidergic agonists, substance P, substance P^Tyr8 and eledoisin-related peptide used intravenously, acted similarly to each other on the submandibular glands of the rats, late in the natural weaning period, but carbachol and physalaemin had slightly different effects. Of the peptidergic agonists, physalaemin was the most potent sialogogue among four tachykinins tested at the low dose. The types of protein secreted by the submandibular glands of the weanling rats in response to all sialogogues used here were typical of the β-type. These results indicate that all agonists used could mainly stimulate the acinar cells of the submandibular glands of the weanling rats which have already fully developed functionally at this time.     

Acquired pure red cell aplasia in a hemodialyzed patient

A 68-year-old male had end-stage renal disease secondary to hypertension. He was placed on chronic dialytic therapy and was given recombinant human erythropoietin (epoetin) for renal anemia. One month later, rapidly progressing anemia was noted. The anemia was unresponsive to maximal doses of epoetin and the patient soon became transfusion-dependent. Erythroid hypoplasia was demonstrated by bone marrow biopsy. A detailed search for the cause of the erythroblastopenia revealed nothing. A diagnosis of acquired pure red cell aplasia was made. The use of immunosuppressive agents improved the patient's symptoms and laboratory data. Antibodies for erythropoietin (EPO) were negative after the treatment. It is suggested that patients with EPO-resistant anemia with no obvious etiology should be examined for underlying hematologic disorders.     

Personality traits affect individual interests in day service activities

Aim: To assess the association of user interest in various activities with personality traits for the provision of activity programs at adult day centers. Methods: A self‐reported questionnaire survey of service users was conducted at 25 day centers in Tokyo; 133 men and 344 women, with a mean age of 81.6 ± 7.9 years, responded. The questionnaire examined their demographics, lifestyles, requested activities, purpose of activity participation, attitudes toward participation, and personality traits by using the BASIC‐3 Personality Inventory (PI)‐short version. Results: The participants with higher sociability and novelty‐seeking scores on the BASIC‐3 PI‐short version requested significantly more activities than those with lower scores. Music appreciation and singing were significantly associated with both sociability and novelty‐seeking facets. The sociability facets were significantly associated with activities, such as walking and interaction with children, while the novelty‐seeking facets were significantly associated with contact with animals and the Internet. There was no significant relationship between the neuroticism facets and any specific activity. Flower arrangement, handicrafts, fashion or make up, cooking, and singing were significantly more frequently requested by the women than by the men, while shogi or mahjong was requested significantly more frequently by the men than by the women. Conclusions: Sociability and novelty‐seeking facets, sex, and age were significantly associated with an interest in particular activities. We recommend that adult day centers create a system under which nurses and formal caregivers fully assess the elderly in order to provide activity programs based on user needs.     

Role of megalin, a proximal tubular endocytic receptor, in the pathogenesis of diabetic and metabolic syndrome-related nephropathies: protein metabolic overload hypothesis

SUMMARY:   Megalin is an endocytic receptor on the apical membranes of proximal tubule cells (PTC) in the kidney, and is involved in the reabsorption and metabolism of various proteins that have been filtered by glomeruli. Patients with diabetes, especially type 2 diabetes, or metabolic syndrome are likely to have elevated serum levels of advanced glycation end products, liver-type fatty acid binding protein, angiotensin II, insulin and leptin, and renal metabolism of these proteins is potentially overloaded. Some of these proteins are themselves nephrotoxic, while others are carriers of nephrotoxic molecules. Megalin is involved in the proximal tubular uptake of these proteins. We hypothesize that megalin-mediated metabolic overload in PTC leads to compensatory cellular hypertrophy and sustained Na⁺ reabsorption, causing systemic hypertension and glomerular hyperfiltration via tubuloglomerular feedback, and named this as 'protein metabolic overload hypothesis'. Impaired metabolism of bioactive proteins such as angiotensin II and insulin in PTC may enhance hypertrophy of PTC and/or Na⁺ reabsorption. Sleep apnoea syndrome, a frequent complication of diabetes and metabolic syndrome, may cause renal hypoxia and result in relative overload of protein metabolism in the kidneys. The development of strategies to identify patients with diabetes or metabolic syndrome who are at high risk for renal metabolic overload would allow intensive treatment of these patients in an effort to prevent the development of nephropathy. Further studies on the intracellular molecular signalling associated with megalin-mediated metabolic pathways may lead to the development of novel strategies for the treatment of nephropathies related to diabetes and metabolic syndrome.