PMID: 

Proc Natl Acad Sci U S A. 1985 Dec ;82(24):8733-6. PMID: 2867545

Abstract Title: 

Pertussis toxin is required for pertussis vaccine encephalopathy.

Abstract: 

A mouse model for encephalopathy induced by pertussis immunization has been described; it has features that closely resemble some of the severe reactions, including seizures and a shock-like state leading to death, occasionally seen after administration of Bordetella pertussis (whooping cough) vaccine. Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin. In this study we have investigated which bacterial determinant is responsible for the encephalopathy. Two lines of evidence implicate pertussis toxin as the active bacterial component. Single-site mutants of B. pertussis with single affected virulence factors were tested. A mutant that produces a defective pertussis toxin had greatly diminished capacity to induce encephalopathy, whereas a hemolysin- and adenylate-cyclase-deficient avirulent mutant had the same activity in the mouse model as a virulent strain. Purified pertussis toxin plus bovine serum albumin was tested and found to induce the lethal encephalopathy, demonstrating that the toxin was the critical constituent of B. pertussis responsible for encephalopathy.

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PMID: 

Vaccine. 2006 Jul 26 ;24(31-32):5779-80. PMID: 15908063

Abstract Title: 

Unexplained cases of sudden infant death shortly after hexavalent vaccination.

Abstract: 

[n/a]

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n/a

PMID: 

Rev Environ Contam Toxicol. 2010 ;203:105-18. PMID: 19957118

Abstract Title: 

The toxic effects of formaldehyde on the nervous system.

Abstract: 

Formaldehyde (FA) is found in the polluted atmosphere of cities, domestic air (e.g., paint, insulating materials, chipboard and plywood, fabrics, furniture, paper), and cigarette smoke, etc.; therefore, everyone and particularly susceptible children may be exposed to FA. FA is also widely used in industrial and medical settings and as a sterilizing agent, disinfectant, and preservative. Therefore, employees may be highly exposed to it in there settings. Of particular concern to the authors are anatomists and medical students, who can be highly exposed to formaldehyde vapor during dissection sessions. Formaldehyde is toxic over a range of doses; chances of exposure and subsequent harmful effects are increased as (room) temperature increases, because of FA's volatility. Many studies have been conducted to evaluate the effects of FA during systemic and respiratory exposures in rats. This review compiles that literature and emphasizes the neurotoxic effects of FA on neuronal morphology, behavior, and biochemical parameters. The review includes the results of some of the authors' work related to FA neurotoxicity, and such neurotoxic effects from FA exposure were experimentally demonstrated. Moreover, the effectiveness of some antioxidants such as melatonin, fish omega-3, and CAPE was observed in the treatment of the harmful effects of FA. Despite the harmful effects from FA exposure, it is commonly used in Turkey and elsewhere in dissection laboratories. Consequently, all anatomists must know and understand the effects of this toxic agent on organisms and the environment, and take precautions to avoid unnecessary exposure. The reviewed studies have indicated that FA has neurotoxic characteristics and systemic toxic effects. It is hypothesized that inhalation of FA, during the early postnatal period, is linked to some neurological diseases that occur in adults. Although complete prevention is impossible for laboratory workers and members of industries utilizing FA, certain precautions can be taken to decrease and/or prevent the toxic effects of FA.

PMID: 

Mol Nutr Food Res. 2019 Oct ;63(20):e1900117. Epub 2019 Aug 12. PMID: 31336403

Abstract Title: 

High-Fat Diet Enriched with Bilberry Modifies Colonic Mucus Dynamics and Restores Marked Alterations of Gut Microbiome in Rats.

Abstract: 

SCOPE: Emerging evidence suggests that high-fat diet (HFD) is associated with gut microbiome dysbiosis and related disorders. Bilberry is a prebiotic food component with known health benefits. Herein, the dynamics of the colonic mucus layer and microbiome during HFD and bilberry supplementation are addressed.METHODS AND RESULTS: The effects on colonic mucus thickness in vivo and gut microbiota composition (Illumina sequencing, quantitative real-time PCR) are investigated in young rats fed a low-fat diet or HFD with or without bilberries for 8 weeks (n = 8). HFD induced significant local colonic effects, despite no observed weight gain or systemic inflammation, as HFD causes epithelial upregulation of inducible nitric oxide synthase, which is counteracted by bilberry. The firmly adherent mucus layer becomes thicker and the mRNA levels of Muc2 and Tff3 are increased by HFD with or without bilberry. In parallel, HFD reduced the colonic abundance of mucolytic bacterial species Akkermansia muciniphila and Bacteroides spp. Finally, bilberry prevents HFD-induced microbiota dysbiosis, including expansion of pathobionts, for example, Enterobacteriaceae.CONCLUSION: HFD expand firmly adherent mucus thickness and reduce mucus-foraging bacteria populations in the colon prior to obesity. Enriching HFD with bilberry protects against intestinal inflammation and marked microbiota encroachment.

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PMID: 

Vaccine. 2013 Jun 7 ;31(25):2738-43. Epub 2013 Apr 11. PMID: 23583892

Abstract Title: 

Pharmacokinetic modeling as an approach to assessing the safety of residual formaldehyde in infant vaccines.

Abstract: 

Formaldehyde is a one-carbon, highly water-soluble aldehyde that is used in certain vaccines to inactivate viruses and to detoxify bacterial toxins. As part of the manufacturing process, some residual formaldehyde can remain behind in vaccines at levels less than or equal to 0.02%. Environmental and occupational exposure, principally by inhalation, is a continuing risk assessment focus for formaldehyde. However, exposure to formaldehyde via vaccine administration is qualitatively and quantitatively different from environmental or occupational settings and calls for a different perspective and approach to risk assessment. As part of a rigorous and ongoing process of evaluating the safety of biological products throughout their lifecycle at the FDA, we performed an assessment of formaldehyde in infant vaccines, in which estimates of the concentrations of formaldehyde in blood and total body water following exposure to formaldehyde-containing vaccines at a single medical visit were compared with endogenous background levels of formaldehyde in a model 2-month-old infant. Formaldehyde levels were estimated using a physiologically-based pharmacokinetic (PBPK) model of formaldehyde disposition following intramuscular (IM) injection. Model results indicated that following a single dose of 200μg, formaldehyde is essentially completely removed from the site of injection within 30 min. Assuming metabolism at the site of injection only, peak concentrations of formaldehyde in blood/total body water were estimated to be 22 μg/L, which is equivalent to a body burden of 66 μg or

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PMID: 

Pol J Vet Sci. 2019 Sep ;22(3):481-487. PMID: 31560462

Abstract Title: 

The influence of bilberry fruit on memory and the expression of parvalbumin in the rat hippocampus.

Abstract: 

Therefore, the aim of the present study was to evaluate the possible effect of bilberry fruit (Vaccinium myrtillus L.) supplement in a daily diet on the cognitive behaviour of the rats and the expression of paravalbumin (PV) in populations of hippocampal neurons. It has been postulated that the antioxidants present in bilberry fruit may act as neuroprotective factors playing also a significant role as memory enhancements. Forty Wistar rats with a similar average body weight (460± 0.4 g) were divided into four groups (n=10 per group). The control group received standard feed (210 g/week), whereas animals of experimental groups received standard feed supplemented with bilberry (per os) at consumed doses of 2 g (group I), 5 g (group II), and 10 g/kg b.w./ /day (group III). After three months of feeding with bilberry, the modified elevated plus-maze test (mEPM) was performed. After 32 weeks of feeding, brains were collected and PV-immunoreactive (ir) neurons were immunohistochemically visualized. In the modified elevated plus-maze test, transfer latency examined 2 h and24 h after the acquisition session was significantly shorter (p⟨0.05) in the group II in comparison with the control group. In CA1 and CA2/CA3 hippocampal fields as well as dentate gyrus of all experimental groups, a significant (p⟨0.05) decrease in number of PV-ir neurons were found. In relation to the control group, the mean subpopulation of PV-ir neurons found in groups II and III were significantly reduced. The subpopulations of PV-ir neurons found in DG of all experimental groups were significantly reduced in comparison to the control. In conclusion the in the present paper we demonstrated a relationship between the diet rich in a bilberry fruit and process of memory as well as numbers of calcium- binding protein-expressing hippocampal neurons. Our results may be source of basic knowledge for further research aiming at neuroprotective role of the bilberry fruit.

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PMID: 

Nutrients. 2019 Nov 25 ;11(12). Epub 2019 Nov 25. PMID: 31775396

Abstract Title: 

An Anthocyanin-Rich Mixed-Berry Intervention May Improve Insulin Sensitivity in a Randomized Trial of Overweight and Obese Adults.

Abstract: 

Evidence supports the beneficial effects of berries on glucoregulation, possibly related to flavonoid content, fiber content, or both. The purpose of this study was to assess the potential of mixed berries to improve insulin sensitivity and to identify the potential role of flavonoids and fiber. In a randomized cross-over trial with four treatment periods, overweight/obese men and women were fed a controlled 45% fat diet for one week prior to a meal-based glucose tolerance test. The same base diet was provided during each feeding period with the addition of one of four treatments: whole mixed berries, sugar matched mixed berry juice, sugar matched gelatin, and sugar/fiber matched gelatin. Subjects then completed a meal-based oral glucose tolerance test. Serum glucose, insulin and non-esterified fatty acids were not different between individual treatments. However, in a secondary analysis, the combined berry preparations resulted in a lower serum insulin area under the curve (difference of 0.15± 0.066 ln pmol min/mL, mean ± SE,= 0.0228), compared to the combined gelatin treatments, while the difference for serum glucose did not quite meet statistical significance (difference of 0.17± 0.093 ln mg·min/dL, mean ± SE,= 0.0738). These results suggest the potential for mixed berry preparations to improve post-prandial insulin response.

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PMID: 

Nutrients. 2019 Nov 26 ;11(12). Epub 2019 Nov 26. PMID: 31779179

Abstract Title: 

Effects of Vitamin D and Calcium Fortified Yogurts on Gait, Cognitive Performances, and Serum 25-Hydroxyvitamin D Concentrations in Older Community-Dwelling Females

Abstract: 

BACKGROUND: Vitamin Dfortified food may improve serum vitamin D level, suggesting that the prevention of adverse consequences of hypovitaminosis D is possible with food fortification. The aim of this randomized controlled trial (RCT) was to examine the effects of vitamin D and calcium fortified yogurt on spatiotemporal gait parameters, cognitive performance, handgrip strength, and serum 25OHD levels in healthy older females.METHODS: Forty older community-dwelling females were recruited in a single-blind, randomized, controlled, superiority clinical trial in two parallel groups (20 participants in the intervention group and 20 in the control group) with intent-to-treat. The intervention group took fortified yogurts daily (i.e., 400 UI of vitamin Dand 800 mg calcium) for 3 months. The non-fortified yogurts contained similar proteins, carbohydrates and lipids, as well as a lower dose of calcium (300 mg) and no vitamin Dsupplementation. Spatiotemporal gait parameters (mean value and coefficient of variation) were assessed using a computerized walkway. Handgrip strength was measured with hydraulic dynamometers. Cognitive performances, including global cognitive functioning assessed with the Mini Mental Status Examination (MMSE) were recorded. All the outcomes were assessed at baseline and at the end of follow-up. The primary outcome was the coefficient of variation of stride time.RESULTS: The intervention group maintained its global cognitive performance and serum 25OHD concentrations, whereas these outcomes decreased (i.e., worst performance) in the control group. The changes in the MMSE score (= 0.022) and serum 25OHD concentrations were different (≤ 0.001) with better values reported in the intervention group compared to the control group. There was no significant change in gait parameters (≥ 0.518) and handgrip strength (≥ 0.600).CONCLUSIONS: Fortified yogurts with vitamin D (i.e., 200 IU) and calcium (i.e., 400 mg) twice a day maintained global cognitive performance and vitamin D status in older females, but not gait performances, signifying that they mainly prevent hypovitaminosis D-related extra-skeletal disorders.

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PMID: 

Food Funct. 2019 Apr 17 ;10(4):2125-2137. PMID: 30924473

Abstract Title: 

Lycopene ameliorates systemic inflammation-induced synaptic dysfunction via improving insulin resistance and mitochondrial dysfunction in the liver-brain axis.

Abstract: 

Systemic inflammation is an important determinant of synaptic dysfunction, but the underlying molecular mechanisms remain elusive. Lycopene (LYC), a major carotenoid present in tomato, is regarded as a nutraceutical that has significant antioxidant and anti-obesity bioactivities. In the current study, we randomly divided 3-month-old C57BL/6J mice into 3 groups: the control, LPS and LPS + LYC groups (LYC, 0.03% w/w, mixed with normal chow) for 5 weeks, and then mice were intraperitoneally injected with LPS (0.25 mg kg-1) for 9 days. Our results demonstrated that LYC supplementation effectively attenuated LPS-elicited neuronal damage and synaptic dysfunction through increasing the expressions of neurotrophic factors and the synaptic proteins SNAP-25 and PSD-95. LYC ameliorated LPS-induced insulin resistance and mitochondrial dysfunction in the mouse brain and liver. LYC alleviated the neuroinflammation and hepatic inflammation. Furthermore, LYC decreased the circulating levels of insulin and proinflammatory mediators LPS, TNF-α, IL-1β and IL-6. In conclusion, these results indicated that the supplementation of LYC might be a nutritional preventive strategy in systemic inflammation-induced synaptic dysfunction.

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PMID: 

Nutrients. 2019 Apr 1 ;11(4). Epub 2019 Apr 1. PMID: 30939781

Abstract Title: 

Lycopene Inhibits Reactive Oxygen Species-Mediated NF-κB Signaling and Induces Apoptosis in Pancreatic Cancer Cells.

Abstract: 

Generation of excess quantities of reactive oxygen species (ROS) caused by mitochondrial dysfunction facilitates rapid growth of pancreatic cancer cells. Elevated ROS levels in cancer cells cause an anti-apoptotic effect by activating survival signaling pathways, such as NF-κB and its target gene expression. Lycopene, a carotenoid found in tomatoes and a potent antioxidant, displays a protective effect against pancreatic cancer. The present study was designed to determine if lycopene induces apoptosis of pancreatic cancer PANC-1 cells by decreasing intracellular and mitochondrial ROS levels, and consequently suppressing NF-κB activation and expression of NF-κB target genes including cIAP1, cIAP2, and survivin. The results show that the lycopene decreased intracellular and mitochondrial ROS levels, mitochondrial function (determined by the mitochondrial membrane potential and oxygen consumption rate), NF-κB activity, and expression of NF-κB-dependent survival genes in PANC-1 cells. Lycopene reduced cell viability with increases in active caspase-3 and the Bax to Bcl-2 ratio in PANC-1 cells. These findings suggest that supplementation of lycopene could potentially reduce the incidence of pancreatic cancer.

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