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Bone Reports Jun 2024Objective Isotretinoin, also known as 13-cis-retinoic acid, is an isomer of tretinoin, the oxidized form of Vitamin A. Orthodontic tooth movement (OTM) is the result of...
Objective Isotretinoin, also known as 13-cis-retinoic acid, is an isomer of tretinoin, the oxidized form of Vitamin A. Orthodontic tooth movement (OTM) is the result of a cascade of inflammatory responses stimulated by a physical element that is the force generated by orthodontic appliances. Isotretinoin is mainly used among adolescents and young adults, and coincidentally it is this age group that also undergoes orthodontic treatment. Materials and Methods Fifty-five animals were used, and they were randomly divided into 11 groups, containing 5 animals in each group. Group 1: Control; Group 2: OTM for 7 days; Group 3: OTM for 14 days; Group 4: Treated with isotretinoin for 14 days with a dosage of 7.5 mg/kg/day; Group 5: Treated with isotretinoin for 14 days with a dosage of 1.0 mg/kg/day; Group 6: Treated with isotretinoin for 21 days with a dosage of 7.5 mg/kg/day; Group 7: Treated with isotretinoin for 21 days with a dosage of 1.0 mg/kg/day; Group 8: Treated with isotretinoin for 14 days with a dosage of 7.5 mg/kg/day and undergoing OTM for 7 days; Group 9: Treated with isotretinoin for 14 days with a dosage of 1.0 mg/kg/day and undergoing OTM for 7 days; Group 10: Treated with isotretinoin for 21 days with a dosage of 7.5 mg/kg/day and undergoing OTM for 14 days; Group 11: Treated with isotretinoin for 21 days with a dosage of 1.0 mg/kg/day and undergoing OTM for 14 days. In Groups 8, 9, 10 and 11, the animals were treated with isotretinoin for 7 days before OTM and maintained during the movement period in the respective groups. Results There was a significant difference in microtomographic parameters, including Trabecular Volume (BV/TV), Trabecular Thickness (Tb.Th), Number of Trabeculae (Tb.N), and Trabecular Separation (Tb.Sp), between the groups. The group that received orthodontic force in conjunction with isotretinoin treatment at a dosage of 7.5 mg/kg/day exhibited lower tooth displacement over a period of 21 days and 14 days. Conclusion Isotretinoin caused a reduction in tooth displacement during OTM when administered at a dose of 7.5 mg/kg/day and isotretinoin did change the microtomographic parameters of treated animals.
PubMed: 38812839
DOI: 10.1016/j.bonr.2024.101775 -
Frontiers in Immunology 2024Porcine epidemic diarrhea virus (PEDV) causes a highly contagious enteric disease with major economic losses to swine production worldwide. Due to the immaturity of the...
Maternal immunization and vitamin A sufficiency impact sow primary adaptive immunity and passive protection to nursing piglets against porcine epidemic diarrhea virus infection.
Porcine epidemic diarrhea virus (PEDV) causes a highly contagious enteric disease with major economic losses to swine production worldwide. Due to the immaturity of the neonatal piglet immune system and given the high virulence of PEDV, improving passive lactogenic immunity is the best approach to protect suckling piglets against the lethal infection. We tested whether oral vitamin A (VA) supplementation and PEDV exposure of gestating and lactating VA-deficient (VAD) sows would enhance their primary immune responses and boost passive lactogenic protection against the PEDV challenge of their piglets. We demonstrated that PEDV inoculation of pregnant VAD sows in the third trimester provided higher levels of lactogenic protection of piglets as demonstrated by >87% survival rates of their litters compared with <10% in mock litters and that VA supplementation to VAD sows further improved the piglets' survival rates to >98%. We observed significantly elevated PEDV IgA and IgG antibody (Ab) titers and Ab-secreting cells (ASCs) in VA-sufficient (VAS)+PEDV and VAD+VA+PEDV sows, with the latter maintaining higher Ab titers in blood prior to parturition and in blood and milk throughout lactation. The litters of VAD+VA+PEDV sows also had the highest serum PEDV-neutralizing Ab titers at piglet post-challenge days (PCD) 0 and 7, coinciding with higher PEDV IgA ASCs and Ab titers in the blood and milk of their sows, suggesting an immunomodulatory role of VA in sows. Thus, sows that delivered sufficient lactogenic immunity to their piglets provided the highest passive protection against the PEDV challenge. Maternal immunization during pregnancy (± VA) and VA sufficiency enhanced the sow primary immune responses, expression of gut-mammary gland trafficking molecules, and passive protection of their offspring. Our findings are relevant to understanding the role of VA in the Ab responses to oral attenuated vaccines that are critical for successful maternal vaccination programs against enteric infections in infants and young animals.
Topics: Animals; Porcine epidemic diarrhea virus; Female; Swine; Pregnancy; Vitamin A; Coronavirus Infections; Antibodies, Viral; Swine Diseases; Immunity, Maternally-Acquired; Adaptive Immunity; Animals, Newborn; Lactation; Dietary Supplements; Vitamin A Deficiency; Immunization
PubMed: 38812505
DOI: 10.3389/fimmu.2024.1397118 -
Frontiers in Nutrition 2024Among commonly performed bariatric surgeries, biliopancreatic diversion with duodenal switch (BPD-DS) provides greater weight loss than Roux-en-Y gastric bypass (RYGB)...
BACKGROUND
Among commonly performed bariatric surgeries, biliopancreatic diversion with duodenal switch (BPD-DS) provides greater weight loss than Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG), with sustained metabolic improvements. However, the risk of long-term nutritional deficiencies due to the hypoabsorptive component of BPD-DS hinders its widespread use.
OBJECTIVE
The aim of the study was to examine nutritional status over 2 years after BPD-DS, RYGB or SG.
METHODS
Patients were recruited in the REMISSION trial (NCT02390973), a single-center, prospective study. Out of 215 patients, 73, 48 and 94, respectively, underwent BPD-DS, RYGB or SG. Weight loss, micronutrient serum levels (including iron, calcium, parathormone, vitamins A, B12 and D), and nutritional supplementation were assessed over 2 years. Patients were supplemented according to the type of surgery and individual micronutrient level evolution.
RESULTS
At baseline, BPD-DS patients were younger than SG patients ( = 0.0051) and RYGB patients had lower body mass index ( < 0.001). Groups had similar micronutrient levels before surgery, with vitamin D insufficiency as the most prevalent nutritional problem (SG: 38.3%, RYGB: 39.9%, BPD-DS: 54.8%, = 0.08). BPD-DS patients showed lower levels of iron, calcium and vitamin A than SG patients at 24 months. Groups had similar levels of vitamin D at 24 months. Prevalence of vitamin D, calcium, iron, vitamin A and vitamin B12 deficiency was similar among groups at 24 months. Rates of vitamin D insufficiency and iron deficiency were lower at 24 months than at baseline. Micronutrient intake was consistent with recommendations in groups post-surgery, but most BPD-DS patients took vitamin A and vitamin D supplement doses above initial recommendations.
CONCLUSION
With appropriate medical and nutritional management, all surgeries led to similar rates of vitamin D, calcium, iron, vitamin A and vitamin B12 deficiencies at 24 months. However, initial vitamin A and vitamin D supplementation recommendations for BPD-DS patients should be revised upwards.
PubMed: 38807643
DOI: 10.3389/fnut.2024.1385510 -
Frontiers in Cellular and Infection... 2024and stand as notorious threats to human beings owing to the myriad of infections they cause. The bacteria readily form biofilms that help in withstanding the effects...
and stand as notorious threats to human beings owing to the myriad of infections they cause. The bacteria readily form biofilms that help in withstanding the effects of antibiotics and the immune system. Intending to combat the biofilm formation and reduce the virulence of the pathogens, we investigated the effects of carotenoids, crocetin, and crocin, on four Staphylococcal strains. Crocetin was found to be the most effective as it diminished the biofilm formation of ATCC 6538 significantly at 50 µg/mL without exhibiting bactericidal effect (MIC >800 µg/mL) and also inhibited the formation of biofilm by MSSA 25923 and at a concentration as low as 2 µg/mL, and that by methicillin-resistant MW2 at 100 µg/mL. It displayed minimal to no antibiofilm efficacy on the Gram-negative strains O157:H7 and as well as a fungal strain of . It could also curb the formation of fibrils, which partly contributes to the biofilm formation in . Additionally, the ADME analysis of crocetin proclaims how relatively non-toxic the chemical is. Also, crocetin displayed synergistic antibiofilm characteristics in combination with tobramycin. The presence of a polyene chain with carboxylic acid groups at its ends is hypothesized to contribute to the strong antibiofilm characteristics of crocetin. These findings suggest that using apocarotenoids, particularly crocetin might help curb the biofilm formation by and
Topics: Biofilms; Carotenoids; Vitamin A; Microbial Sensitivity Tests; Anti-Bacterial Agents; Staphylococcus epidermidis; Candida albicans; Staphylococcus aureus; Humans; Pseudomonas aeruginosa; Staphylococcus
PubMed: 38803574
DOI: 10.3389/fcimb.2024.1404960 -
Cell Communication and Signaling : CCS May 2024A promising new therapy option for acute kidney injury (AKI) is mesenchymal stem cells (MSCs). However, there are several limitations to the use of MSCs, such as low...
A promising new therapy option for acute kidney injury (AKI) is mesenchymal stem cells (MSCs). However, there are several limitations to the use of MSCs, such as low rates of survival, limited homing capacity, and unclear differentiation. In search of better therapeutic strategies, we explored all-trans retinoic acid (ATRA) pretreatment of MSCs to observe whether it could improve the therapeutic efficacy of AKI. We established a renal ischemia/reperfusion injury model and treated mice with ATRA-pretreated MSCs via tail vein injection. We found that AKI mice treated with ATRA-MSCs significantly improved renal function compared with DMSO-MSCs treatment. RNA sequencing screened that hyaluronic acid (HA) production from MSCs promoted by ATRA. Further validation by chromatin immunoprecipitation experiments verified that retinoic acid receptor RARα/RXRγ was a potential transcription factor for hyaluronic acid synthase 2. Additionally, an in vitro hypoxia/reoxygenation model was established using human proximal tubular epithelial cells (HK-2). After co-culturing HK-2 cells with ATRA-pretreated MSCs, we observed that HA binds to cluster determinant 44 (CD44) and activates the PI3K/AKT pathway, which enhances the anti-inflammatory, anti-apoptotic, and proliferative repair effects of MSCs in AKI. Inhibition of the HA/CD44 axis effectively reverses the renal repair effect of ATRA-pretreated MSCs. Taken together, our study suggests that ATRA pretreatment promotes HA production by MSCs and activates the PI3K/AKT pathway in renal tubular epithelial cells, thereby enhancing the efficacy of MSCs against AKI.
Topics: Acute Kidney Injury; Animals; Mesenchymal Stem Cells; Tretinoin; Humans; Mice; Mesenchymal Stem Cell Transplantation; Male; Mice, Inbred C57BL; Hyaluronic Acid; Hyaluronan Receptors; Proto-Oncogene Proteins c-akt; Cell Line; Phosphatidylinositol 3-Kinases; Signal Transduction; Reperfusion Injury; Disease Models, Animal; Apoptosis
PubMed: 38802835
DOI: 10.1186/s12964-024-01671-1 -
Cureus May 2024Background Assessing micronutrient intake is important in identifying deficiencies that may contribute to insulin resistance, poor glycemic control, and increased risk...
Background Assessing micronutrient intake is important in identifying deficiencies that may contribute to insulin resistance, poor glycemic control, and increased risk of diabetes-related complications. The study's objectives were to evaluate micronutrient intake in prediabetes (PD) and type 2 diabetes (T2DM) patients compared to recommended dietary intakes (RDI) and to determine the associations between the micronutrient patterns and both anthropometric measurements and biomarkers of diabetes. Methods This cross-sectional study was conducted on 349 patients with T2DM and 252 patients with PD. Micronutrient intake was evaluated using a validated food frequency questionnaire. Micronutrient patterns were extracted from factor analysis using principal component analysis with varimax rotation. Participants in the highest tertile were considered to have the highest adherence to the corresponding micronutrient pattern. Results T2DM patients had a significantly lower intake of vitamin E (9.4 ± 0.2 vs. 10.1 ± 0.3 mg; p = 0.048), vitamin D (44.3 ± 1.1 vs. 48.9 ± 1.7 IU; p = 0.020), and thiamin (1.3 ± 0.1 vs. 1.4 ± 0.1 mg; p = 0.013) compared to PD patients. All patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium and a significantly higher intake of vitamin B12 and copper compared to RDI. Three distinct micronutrient patterns were identified within each group. In the PD group, the Fe-Mn-Se pattern correlated significantly with waist circumference (WC) and fasting plasma glucose (FPG). The Vit.C-K-Folate pattern showed significant associations with body fat (BF). The Vit.B2-P-Vit.B12 pattern was significantly linked to WC, body mass index (BMI), BF, FPG, and serum insulin (SI). For the T2DM patients, the K-Folate-Mg pattern displayed an inverse and significant association with weight and WC. The Iron-Se-Vit.B3 pattern showed a significant association with low-density lipoprotein (LDL) cholesterol, triglycerides, and total cholesterol. The Vit.B2-P-Ca pattern was significantly associated with fasting plasma glucose (FPG). Conclusion This study demonstrated that T2DM patients had significantly lower vitamin E, vitamin D, and thiamin intake than PD patients. Both T2DM and PD patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium compared to the RDI. Among the identified micronutrient patterns, only the K-Folate-Mg pattern exhibited a significant association with reduced body weight and WC.
PubMed: 38800767
DOI: 10.7759/cureus.60906 -
Journal of Medical Case Reports May 2024All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous... (Review)
Review
A rare incidence of severe dermatological toxicities triggered by concomitant administration of all-trans retinoic acid and triazole antifungal in patients with acute promyelocytic leukemia: a case series and review of the literature.
BACKGROUND
All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous xerosis, rash, and pruritus are well reported, ATRA associated severe dermatological toxicities are extremely rare. ATRA is primary metabolized by cytochrome P450 (CYP450) enzyme system, and triazole antifungals are notorious for their strong inhibitory effect on CYP450.
CASE PRESENTATION
Three Asian APL patients experienced rare ATRA-induced severe dermatological toxicities: exfoliative dermatitis (ED) in cases 1 and 2, and necrotic scrotal ulceration in case 3. Both case 1 (33-year-old female), and case 2 (28-year-old male) landed in emergency department with dehydration, generalized skin erythema and xerosis during their induction chemotherapy. Both of these patients also developed invasive aspergillosis and required concomitant triazole antifungals during their chemotherapy. For ED, intravenous fluids and broad-spectrum antibiotics were started along with application of local emollients to prevent transdermal water loss. Although their general condition improved but skin exfoliation continued with complete desquamation of palms and soles. Dermatology was consulted, and clinical diagnosis of ED was established. Discontinuation of ATRA resulted in complete resolution of ED. Case 3 (15-year-old boy) reported two blackish mildly tender scrotal lesions during induction chemotherapy. He also had mucocutaneous candidiasis at presentation and was kept on triazole antifungal. Local bacterial & fungal cultures, and serological testing for herpes simplex virus were reported negative. Despite adequate local care and optimal antibiotic support, his lesions persisted, and improved only after temporary discontinuation of ATRA. After a thorough literature review and considering the temporal association of cutaneous toxicities with triazole antifungals, we speculate that the concomitant use of triazole antifungals inhibited the hepatic metabolism of ATRA, resulting in higher serum ATRA concentration, and markedly accentuated cutaneous toxicities in our patients.
CONCLUSION
By highlighting this crucial pharmacokinetic interaction, we want to caution the fellow oncologists to be mindful of the inhibitory effect of triazole antifungals on CYP450. We propose using a non-myelosuppressive combination of ATRA and arsenic trioxide for management of APL hence, obliterating the need of prophylactic antifungals. However, in the event of invasive fungal infection (IFI), we suggest using alternative class of antifungals.
Topics: Humans; Leukemia, Promyelocytic, Acute; Male; Antifungal Agents; Female; Tretinoin; Adult; Triazoles; Antineoplastic Agents; Aspergillosis; Drug Eruptions
PubMed: 38797854
DOI: 10.1186/s13256-024-04577-1 -
Food Chemistry Oct 2024Fatty acid (FA), carotenoid and vitamin contents of UK eggs were assessed for four production systems (caged (CA), free-range (FR), organic (OR) and extensive organic...
Fatty acid (FA), carotenoid and vitamin contents of UK eggs were assessed for four production systems (caged (CA), free-range (FR), organic (OR) and extensive organic (EO)) as well as season. The impact of enforced housing, due to avian influenza, was also investigated. Production system did not alter vitamin D, B or B content, but significantly influenced nutritionally desirable FA, carotenoid and vitamins A and E - concentrations decreased as production intensity increased, although for most, CA and FR did not differ significantly. Vitamin E and FA profiles for OR and EO were also similar, although carotenoids were higher in EO eggs. In contrast, FA, carotenoids, vitamins E and B were consistent throughout the year, unlike vitamins A, D and B, which fluctuated with season; D and B were higher in July than January and lower vitamin A was the only detected implication from enforced housing of FR and OR birds.
Topics: Eggs; United Kingdom; Animals; Nutritive Value; Vitamins; Carotenoids; Chickens; Fatty Acids; Seasons
PubMed: 38795627
DOI: 10.1016/j.foodchem.2024.139783 -
Nutrients May 2024In Japan, many workers are exposed to chronic stress, sleep deprivation, and nutritional imbalance. They tend still to go to work when ill, leading to decreased work...
In Japan, many workers are exposed to chronic stress, sleep deprivation, and nutritional imbalance. They tend still to go to work when ill, leading to decreased work performance and productivity, which has become a major social problem. We conducted a human entry study with the aim of finding a link between these two factors and proposing an optimized diet, believing that a review of diet may lead to an improvement in labor productivity. In this study, we used subjective accomplishment (SA) as a measure of productivity. First, we compared nutrient intake between groups with high and low SA using data from a health survey of 1564 healthy male and female adults. Significant differences were found in the intake of 13 nutrients in males and 15 nutrients in females, including potassium, vitamin A, insoluble fiber, and biotin. Recommended daily intake of these nutrients was determined from survey data. Next, we designed test meals containing sufficient amounts of 17 nutrients and conducted a single-arm intervention study (registration code UMIN000047054) in Kameyama City, Mie Prefecture, Japan. Healthy working adults (males and females aged 20-79 years) were recruited and supplied with test meals, which were eaten once a day 5 days a week for 8 weeks. SA was significantly higher and daytime sleepiness (DS) was significantly lower after lunch on workdays in younger participants (under 60 years) when they ate the test meals as breakfast or lunch. Our results suggest that SA and DS, which change daily, are strongly influenced by the meal eaten before work, and that taking the 17 nutrients may help prevent presenteeism and improve labor productivity.
Topics: Humans; Male; Female; Adult; Middle Aged; Japan; Aged; Nutrients; Young Adult; Health Surveys; Efficiency; Diet; Work Performance; Meals
PubMed: 38794648
DOI: 10.3390/nu16101410 -
Pharmaceutics Apr 2024The development of numerous drugs is often arrested at clinical testing stages, due to their unfavorable biopharmaceutical characteristics. It is the case of fenretinide... (Review)
Review
The development of numerous drugs is often arrested at clinical testing stages, due to their unfavorable biopharmaceutical characteristics. It is the case of fenretinide (4-HPR), a second-generation retinoid, that demonstrated promising in vitro cytotoxic activity against several cancer cell lines. Unfortunately, response rates in early clinical trials with 4-HPR did not confirm the in vitro findings, mainly due to the low bioavailability of the oral capsular formulation that was initially developed. Capsular 4-HPR provided variable and insufficient drug plasma levels attributable to the high hepatic first-pass effect and poor drug water solubility. To improve 4-HPR bioavailability, several approaches have been put forward and tested in preclinical and early-phase clinical trials, demonstrating generally improved plasma levels and minimal systemic toxicities, but also modest antitumor efficacy. The challenge is thus currently still far from being met. To redirect the diminished interest of pharmaceutical companies toward 4-HPR and promote its further clinical development, this manuscript reviewed the attempts made so far by researchers to enhance 4-HPR bioavailability. A comparison of the available data was performed, and future directions were proposed.
PubMed: 38794242
DOI: 10.3390/pharmaceutics16050579