Protective effect of propolis against aluminum chloride-induced reproductive toxicity in male rats

The aim of the present study was to investigate the toxic effects of aluminum chloride (AlCl3) on the reproductive organs, as well as, the protective effect of propolis against AlCl3-induced reproductive toxicity in male rats. Eighty adult male fertile Sprague Dawley albino rats were randomly divided into four groups of 20 each. Group 1: served as control group and received only distilled water. Group 2: received a daily ingestion of 80 mg/kg of AlCl3. Group 3: received a daily ingestion of 200 mg/kg of an ethanol extract of propolis. Group 4: received a daily ingestion of 80 mg/kg of AlCl3 in addition to 200 mg/kg of an ethanol extract of propolis. The duration of experiment was six weeks. At the end of the experiment, the testes, seminal vesicles, prostate glands and epididymides were dissected out, and weighed. Sperm characteristics were evaluated and plasma testosterone level was estimated. There were no significant changes between the control and the propolis-treated group. AlCl3-treated group showed a highly significant decrease in the index weights of testes and prostate glands, a highly significant lower sperm count, motility and viability, a highly significant increase in the number of abnormal sperms, as well as, a highly significant decrease in serum testosterone level (p < 0.001), compared to control. Rats of AlCl3+propolis-treated group showed a highly significant improvement in all previous alterations. In conclusion, propolis appeared to ameliorate AlCl3-induced reproductive toxicity in male rats.

Occurrence of Phthalates in Bottled Drinks in the Chinese Market and Its Implications for Dietary Exposure

Ubiquitous occurrences of phthalic acid esters (PAEs) or phthalates in a variety of consumer products have been demonstrated. Nevertheless, studies on their occurrence in various types of bottled drinks are limited. In this study, fifteen PAEs were analyzed in six categories of bottled drinks (n = 105) collected from the Chinese market, including mineral water, tea drinks, energy drinks, juice drinks, soft drinks, and beer. Among the 15 PAEs measured, DEHP was the most abundant phthalate with concentrations ranging from below the limit of quantification (LOQ) to 41,000 ng/L at a detection rate (DR) of 96%, followed by DIBP (DR: 88%) and DBP (DR: 84%) with respective concentration ranges of below LOQ to 16,000 and to 4900 ng/L. At least one PAE was detected in each drink sample, and the sum concentrations of 15 PAEs ranged from 770 to 48,004 ng/L (median: 6286 ng/L). Significant differences with respect to both PAE concentrations and composition profiles were observed between different types of bottled drinks. The median sum concentration of 15 PAEs in soft drinks was over five times higher than that detected in mineral water; different from other drink types. Besides DEHP, DBIP, and DBP, a high concentration of BMEP was also detected in a tea drink. The estimated daily dietary intake of phthalates (EDIdrink) through the consumption of bottled drinks was calculated based on the concentrations measured and the daily ingestion rates of bottled drink items. The EDIdrink values for DMP, DEP, DIBP, DBP, BMEP, DAP, BEEP, BBP, DCP, DHP, BMPP, BBEP, DEHP, DOP, and DNP through the consumption of bottled mineral water (based on mean concentrations) were 0.45, 0.33, 12.5, 3.67, 2.10, 0.06, 0.32, 0.16, 0.10, 0.09, 0.05, 0.81, 112, 0.13, and 0.20 ng/kg-bw/d, respectively, for Chinese adults. Overall, the EDIdrink values calculated for phthalates through the consumption of bottled drinks were below the oral reference doses suggested by the United States Environmental Protection Agency (U.S. EPA).

Administration of Ligilactobacillus salivarius MP101 in an Elderly Nursing Home during the COVID-19 Pandemic: Immunological and Nutritional Impact

The elderly population living in nursing homes is particularly vulnerable to COVID-19 although individual susceptibility to SARS-CoV-2 infection may be related to the host microbiota. The objective of this work was to investigate the effect of Ligilactobacillus salivarius MP101 on the functional (Barthel index), cognitive (GDS/FAST), and nutritional (MNA) status as well as on the nasal and fecal inflammatory profiles of elderly residents living in a nursing home that is highly affected by COVID-19. A total of 25 residents participated in the trial, which involved the daily ingestion of a dairy product (L. salivarius MP101: 9.3 log10 CFU per unit) for 4 months. Nasal and fecal samples were analyzed for 37 immune factors at recruitment and at the end of the study. After the trial, no change in the GDS/FAST scores were found but, in contrast, the values for the Barthel index and the MNA score improved significantly. The concentrations of some immune factors changed significantly after the trial, including a decrease in the concentrations of BAFF/TNFSF13B, APRIL/TNFSF13, IL8, IL31, osteopontin, sTNF-R1, and sTNF-R2, and an increase in chitinase 3-like 1, IL19, IL35, and pentraxin 3 was also observed. In conclusion, L. salivarius MP101 seems to be a promising strain for improving or maintaining health in this highly vulnerable population.

Vitamin D Supplements: Over-the-Counter Accessibility... It Is Safe?

Calcium is the fifth most abundant element in earth and human body. It has multiple functions within our system such bone mineralization, neuromuscular excitability regulation, hemostasis, membrane transport, release of hormones and neurotransmitters, among others. For duodenal absorption of calcium, we need vitamin D, reason for which supplementation of both components is important to maintain adequate calcium homeostasis. However, it is entirely beneficial or can be harmful? As we know everything in excess has its consequences, as we describe below. 72 y/o male is brought to the ED after relative find him lethargic, she reports noticing generalized weakness that has been progressing over weeks, prominent in upper extremities with associated increased in urinary frequency. Patient past medical history is relevant for CAD, hypothyroidism, dyslipidemia, and DMT2. On physical examination patient is found hypoactive, but arousable to verbal stimuli, without distress, focal neurologic deficit, thyromegaly nor lymphadenopathy. Presents with Ca+: 18.8mg/dL (n:8.0–10.5mg/dL), that could explain patient clinical presentation for which workup for hypercalcemia is done finding PTH suppress: 14.57pg/mL (n:15-65pg/mL). Patient now with non-PTH related hypercalcemia is further evaluated and found with negative UPEP and SPEP ruling out multiple myeloma and PTH-rp &lt;2.0pmol/L (negative). While etiology of severe hypercalcemia is being study, patient complications of it are being managed such as AKI stage 3 as he presents with Cr: 3.85mg/dL, BUN: 62.5, CrCl:18ml/min and GFR: 15ml/min. Aggressive IV hydration and bisphosphonate therapy failed to decrease calcium and renal function continues worsens, for which hemodialysis is required for calcium clearance. Patient then found with vitamin D25-OH levels: 210.4ng/mL (n:30-100ng/mL), upon questioning he reports taking multivitamins and supplements equivalent for a daily ingestion of 50,700IU of Vitamin D3 and 334mg of calcium carbonate. Patient calcium levels normalize after dialysis but develops renal failure for which he has to be discharged on permanent hemodialysis. Although prevalence is unknown, hypercalcemia due to vitamin D intoxication is relatively uncommon in comparison to hyperparathyroidism and malignancy. An exact dose intake that leads to intoxication has not yet being stablished but supplementation besides dosage is also dependent on duration of therapy. This case has a lot to teach us, starting with detrimental effects of hypercalcemia, follow by the consequences of lack of counseling and close follow-up of patient over-the-counter supplementation. As physicians we should inquire more about OTC medications and supplements our patients are taking not only for intoxication concerns, but also for drugs interactions. Counseling must be the cornerstone of our practice to avoid life changing consequences as in this case.

Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

Intake of Seven Essential Amino Acids Improves Cognitive Function and Psychological and Social Function in Middle-Aged and Older Adults: A Double-Blind, Randomized, Placebo-Controlled Trial

Background: To delay the onset of dementia, it is important for healthy adults to take preventive actions before the cognitive function clearly declines. Protein malnutrition is a potential risk factor for senile dementia, although the precise link between protein/amino acid nutrition and cognitive function is unknown. The purpose of this study was to examine the effect of the ingestion of seven selected essential amino acids as a granular powder, namely, leucine, phenylalanine, and lysine supplemented with isoleucine, histidine, valine, and tryptophan on cognitive and psychosocial functions in healthy adults.Methods: A double-blind, randomized, placebo-controlled trial was conducted. A total of 105 participants aged 55 years or older were randomly assigned to one of three groups: daily ingestion of 3 g (3gIG) or 6 g (6gIG) of the selected amino acids or daily ingestion of a placebo (PCG). Each group ingested the test powder for 12 weeks. As the main outcome, cognitive function was assessed before and after ingestion by a cognitive test battery. Psychosocial functions were also examined.Results: The numbers of participants excluding dropouts were 35 in PCG and 3gIG and 33 in 6gIG. Analysis of covariance revealed that the 6gIG showed significantly improved cognitive function (Trail Making Test B), social interaction and psychological health scores after ingestion compared to the PCG (multiplicity adjusted p &lt; 0.05).Conclusions: Current findings suggested that ingestion of the seven essential amino acids led to improved attention and cognitive flexibility and psychosocial functioning, which is expected to prevent cognitive decline.Clinical Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037779, Identifier: UMIN000033174).

On the Digital Psychopharmacology of Valproic Acid in Mice

ObjectiveAntiepileptic drugs (AEDs) require daily ingestion for maximal seizure prophylaxis. Adverse psychiatric consequences of AEDs present as: (i) reversible changes in mood, anger, anxiety and/or irritability that often necessitate drug discontinuation, and (ii) autism and/or cognitive/psychomotor developmental delays following fetal exposure. Technical advances in quantifying naturalistic rodent behaviors may provide sensitive preclinical estimates of AED psychiatric tolerability and neuropsychiatric teratogenicity.MethodsUsing instrumented home-cage monitoring, we assessed how valproic acid (VPA, dissolved in sweetened drinking water) alters home-cage behavior in adult C57BL/6J mice and in the adult offspring of VPA-exposed breeder pairs. By utilizing a pup open field assay, we also examined how prenatal VPA exposure impacts early spontaneous exploratory behavior.ResultsAt 500-600mg/kg/d, chronic VPA produced hyperphagia and increased wheel-running without impacting sleep, activity and measures of risk aversion. When applied chronically to breeder pairs of mice, VPA prolonged the latency to viable litters without affecting litter size. Two-week old VPA-exposed pups displayed open field hypoactivity without alterations in thigmotaxis. As adults, prenatal VPA-exposed mice displayed active state fragmentation, hypophagia and increased wheel running, together with subtle alterations in home-cage dyadic behavior.InterpretationThrough automated home-cage assessments of C57BL/6J mice, we capture an ethologically centered psychopharmacological profile of enterally administered VPA that is aligned with human clinical experience. By characterizing the effects of pangestational VPA exposure, we discover novel murine expressions of pervasive neurodevelopment. Incorporating rigorous comprehensive assessments of neuropsychiatric tolerability may inform the design of future AEDs with improved neuropsychiatric safety profiles, both for patients and their offspring.