Modulation of human lymphocyte proliferative response with aging.

Previously, we have demonstrated age-associated alterations in transmembrane signaling. One of the most reproducible alterations found in the immune response with aging is the decrease of lymphocyte proliferation on stimulation with various different mitogens. Here, we confirm that proliferative responses to stimulation with phytohaemagglutin (PHA), recombinant human IL-2, or anti-CD3 monoclonal antibody are all greater in the young (20-25 years) than old (60-87 years) population. We attempted to modulate the proliferative response using various agents acting at different levels of transmembrane signaling (pertussis toxin, cholera toxin, isoproterenol, PMA, Ca ionophore A23187), as well as at the level of the lymphocyte plasma membrane (methyl-beta-cyclodextrin, MBCD), or by using antioxidant vitamins (Vitamin E or C). None of these agents was able to restore effectively the proliferative response of lymphocytes from the aged to the level of young subjects. Even the combination of A23187 and PMA acting directly on calcium metabolism and protein kinase C activity was insufficient to restore the decreased mitogenic capacity of T cells from elderly subjects. Cyclodextrin, which decreases the cholesterol content of the membrane, increased the proliferative response of lymphocytes of elderly subjects, but not to the level of the young. Vitamin E had a very strong inhibitory effect on lymphocyte stimulation in both the age groups, except in combination with MBCD in T cells of the elderly, while Vitamin C had no significant modulatory effect. MAPK ERK and p38 activation was found to be decreased with aging in T cells after anti-CD3 mAb stimulation. Vitamin E but not Vitamin C strongly inhibited MAPK ERK or p38 activation. The direct activation of certain molecules or the modulation of the cholesterol content of the membrane seems to be effective immunomodulatory interventions with aging.     

Insulin-like growth factor-I receptors in human brain and pituitary gland: An autoradiographic study

Insulin-like growth factor (IGF)-I receptors were studied in adult human postmortem brain and pituitary gland using quantitative autoradiography with human recombinant [¹²⁵I]IGF-I. The highest densities were found in the choroid plexus, pituitary gland-where IGF-I receptors were mainly concentrated in the anterior lobe, pineal gland, glomerular layer of the olfactory bulb, and the molecular layer of the cerebellar cortex. Moderate densities were present in cerebral cortex, caudate nucleus, putamen, accumbens, the CA1, CA2, CA3 fields and dentate gyrus of the hippocampus, the dendate nucleus of the cerebellum, amygdala, thalamus, pontine nuclei, and substantia nigra. All other brain areas, including white matter, contained low densities of IGF-I receptors. The finding that several well-defined brain structures are enriched with IGF-I receptors suggests a rieurotrophic/survival or neuromodulatory role of insulin-like growth factors on specific neuronal systems. IGF-I receptors observed in the white matter may be associated with oligodendrocytes. © 1994 Wiley-Liss, Inc.     

Iron Status is Associated with Mood,Cognition, and Functional Ability in Older Adults: A Cross-Sectional Study

Several conditions are risk factors for iron deficiency (ID), some of which are highly prevalent in older individuals. Despite the amount of evidence pointing for a role of ID in cognition, mood and physical functional ability, the research addressing these associations in older individuals is still scarce. In the present study, 162 older community-dwelling individuals (29.53% classified as ID) were enrolled in a cross-sectional analysis and characterized regarding cognition, mood, functional ability, general nutritional intake and iron status. Assessment of iron status was performed using several blood biomarkers. Storage and erythropoiesis dimensions were positively associated with memory, along with an interaction (moderator effect) between iron storage and nutritional status. A more depressed mood was negatively associated with (iron) transport, transport saturation and erythropoiesis dimensions, and functional tiredness was positively associated with the erythropoiesis dimension. These observations indicate that lower iron status is associated with depressive mood, functional tiredness and poorer memory ability, with the latter moderated by nutritional status. These findings suggest that using iron as a continuous variable may be useful in finding associations with iron homeostasis, eventually missed when iron levels are considered within the usual classification groups.     

Beeinflussung der psychosozialen Entwicklung von Kindern und Jugendlichen durch das Tragen von Gesichtsmasken im öffentlichen Raum zur Prävention von Infektionskrankheiten: Ein systematischer Review

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Zur Prävention tröpfchenübertragener Infektionskrankheiten wird das Tragen einer Maske im öffentlichen Raum...     

The Health Effects of Vitamin D and Probiotic Co-Supplementation: A Systematic Review of Randomized Controlled Trials

Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment were conducted. Seven randomized controlled trials were included, which had low risk of bias. Six studies were double-blind, and once single-blind, extended over 6–12 weeks, and included 50–105 participants. Conditions explored included schizophrenia, gestational diabetes, type 2 diabetes and coronary heart disease, polycystic ovarian syndrome, osteopenia, irritable bowel syndrome (IBS), and infantile colic. Supplementation frequency was daily or bi-monthly, with mainly vitamin D3, and Lactobacillus, Bifidobacterium, and Streptococcus. Comparators were placebo, vitamin D, lower vitamin D dose, and probiotics and lower vitamin D dose. The co-supplementation yielded greater health benefits than its comparators did in all studies except in one assessing IBS. Beneficial effects included decreased disease severity, improved mental health, metabolic parameters, mainly insulin sensitivity, dyslipidemia, inflammation, and antioxidative capacity, and lower use of healthcare. Co-supplementation of vitamin D and probiotics generated greater health benefits than its comparators did. More studies in other diseases and various populations are needed to confirm these findings and to elucidate the optimal form, composition, and frequency of this co-supplementation.     

Comparison of hybrid <Superscript>68</Superscript>Ga-PSMA-PET/CT and <Superscript>99m</Superscript>Tc-DPD-SPECT/CT for the detection of bone metastases in prostate cancer patients: <Emphasis Type="Italic">Additional value of morphologic information from low dose CT</Emphasis>

Purpose

This study compared ⁶⁸Gallium-prostate-specific-membrane-antigen based Positron-emission-tomography (⁶⁸Ga-PSMA-PET) and ^99metastabletechnetium-3,3-diphospho-1,2-propanedicarbonacid (^99mTc-DPD-SPECT) in performing skeletal staging in prostate cancer (PC) patients and evaluated the additional value of the information from low-dose-computed tomography (CT).

Materials and Methods

In this retrospective study, 54 patients who received ⁶⁸Ga-PSMA-PET/CT and ^99mTc-DPD-SPECT/CT within 80 days were extracted from our database. Osseous lesions were classified as benign, malignant or equivocal. Lesion, region and patient based analysis was performed with and without CT fusion. The reference standard was generated by defining a best valuable comparator (BVC) containing information from all available data.

Results

In the patient based analysis, accuracies measured as “area-under-the-curve” (AUC) for ⁶⁸Ga-PSMA-PET, ^99mTc-SPECT, ⁶⁸Ga-PSMA-PET/CT and ^99mTc-SPECT/CT were 0.97-0.96, 0.86-0.83, 1.00 and 0.83, respectively (p<0.05) (ranges = optimistic vs. pessimistic view). Region based analysis resulted in the following sensitivities and specificities: 91.8-97.7%, 100-99.5% (PET); 61.2-70.6%, 99.8-98.3% (SPECT); 97.7%, 100% (PET/CT), 69.4% and 98.3% (SPECT/CT) (p<0.05). The amount of correct classifications of equivocal lesions by CT was significantly higher in PET (100%) compared to SPECT (52.4%) (p<0.05).

Conclusion

⁶⁸Ga-PSMA-PET outperforms ^99mTc-DPD-SPECT in detecting bone metastases in PC patients. Additional information from low-dose-CT resulted in a significant reduction in equivocal lesions in both modalities, however ⁶⁸Ga-PSMA-PET benefited most.

Key Points

? Ga-PSMA-PET outperforms ^99m Tc-DPD-SPECT in skeletal staging in prostate cancer patients ? Proportion of equivocal decisions was significantly reduced by CT-fusion in both modalities ? Ga-PSMA-PET benefits more from CT information, compared to ^99m Tc-DPD-SPECT