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12 pages, 564 KiB  
Article
Real-World Treatment Efficacy and Safety Profile of Sofosbuvir- and Velpatasvir-Based HCV Treatment in South Korea: Multicenter Prospective Study
by Jae Hyun Yoon, Chang Hun Lee, Hoon Gil Jo, Ju-Yeon Cho, Jin Dong Kim, Jin Won Kim, Ga Ram You, Sung Bum Cho and Sung Kyu Choi
Viruses 2025, 17(7), 949; https://doi.org/10.3390/v17070949 - 4 Jul 2025
Viewed by 609
Abstract
Background: The advent of direct-acting antivirals (DAAs) has marked a significant milestone in the therapeutic landscape of hepatitis C, greatly improving treatment efficacy. A therapeutic regimen encompassing sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) has demonstrated strong efficacy across all genotypes of the [...] Read more.
Background: The advent of direct-acting antivirals (DAAs) has marked a significant milestone in the therapeutic landscape of hepatitis C, greatly improving treatment efficacy. A therapeutic regimen encompassing sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) has demonstrated strong efficacy across all genotypes of the hepatitis C virus (HCV) and has recently been incorporated into the Korean healthcare system. This study aimed to evaluate the real-world efficacy and safety of these antivirals in the South Korean population. Methods: This prospective, multicenter, observational study enrolled patients with chronic HCV treated with SOF/VEL-based regimens at six hospitals between November 2022 and January 2024. DAA-naïve patients received SOF/VEL ± ribavirin for 12 weeks. Patients who had failed prior DAA therapy received SOF/VEL/VOX for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks post-treatment (SVR12). Results: Among 101 patients treated with SOF/VEL, the mean age was 64.71 years, and 40.9% were male. Genotypes 1b and 2 were identified in 40.6% and 59.4% of patients, respectively. Two patients had a history of interferon-based treatment. The mean baseline HCV RNA level was 3,088,097 IU/mL. Cirrhosis was observed in 26.7% of patients (21.8% compensated; 5.0% decompensated). Of the 101 patients, 12 were lost to follow-up. Among the 89 patients who completed follow-up, SVR12 was achieved in 100.0% (89/89), including 5 patients with decompensated cirrhosis. In the SOF/VEL/VOX group, 17 patients were treated. The mean age was 61.84 years, 29.4% were male, and four had compensated cirrhosis. One patient was lost to follow-up. SVR12 was achieved in 100.0% (16/16) of the patients who completed follow-up. No serious adverse events (≥grade 3) were reported in either group during the DAA treatment period. Conclusions: In this first prospective real-world study in South Korea, SOF/VEL-based regimens demonstrated excellent efficacy and safety, achieving 100% SVR12 in the per-protocol population, including patients with cirrhosis and prior treatment failure. Full article
(This article belongs to the Special Issue Advancing Hepatitis Elimination: HBV, HDV, and HCV)
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24 pages, 3016 KiB  
Article
Safety and Efficacy of Loading Doses of Vitamin D: Recommendations for Effective Repletion
by Béla E. Tóth, István Takács, Kristóf Kádár, Sara Mirani, Miklós Vecsernyés and Péter Lakatos
Pharmaceuticals 2024, 17(12), 1620; https://doi.org/10.3390/ph17121620 - 30 Nov 2024
Cited by 1 | Viewed by 7639
Abstract
Background/Objectives: Epidemiological data on vitamin D status revealed that, despite various dosage and durations of supplementation, the effectiveness often fails to achieve optimal outcomes. The need for higher doses than previously recommended was suggested, but several modifying factors should be considered, including the [...] Read more.
Background/Objectives: Epidemiological data on vitamin D status revealed that, despite various dosage and durations of supplementation, the effectiveness often fails to achieve optimal outcomes. The need for higher doses than previously recommended was suggested, but several modifying factors should be considered, including the level of deficiency, and BMI. The objectives of this post hoc evaluation are to characterize treatment effectiveness based on the applied dose, duration and BMI; and to assess the safety aspects associated with rapid repletion of vitamin D. Methods: Vitamin D deficient subjects selected in the post-hoc analysis: seventy patients included from a combined loading-maintenance supplementation (300,000 IU followed by 60,000 IU) protocol and 62 deficient subjects who received a low-dose maintenance (1000 IU/day) therapy. The risk of overload and the incidence of hypercalciuria and hypercalcemia resulting from loading or post-loading maintenance were investigated. Results: The moderate–fast-loading schedule of 60,000 IU per week for 5 weeks, effectively achieves the target in 25(OH)D levels over 30 ng/mL for all deficient subjects, regardless of their BMI. Slower loading with lower weekly doses confirms the safety of supplementation, but the effectiveness is dependent on the subjects’ BMI; overweight and obese patients require higher doses to reach the same vitamin D levels. No difference in safety parameters observed compared to low-dose therapies. Conclusions: The loading treatment involving a total dose of 300,000 IU administered over 5 or 10 weeks is effective for repletion, does not lead to 25(OH)D overload, and poses no additional risks of hypercalcemia or hypercalciuria. Furthermore, there are no safety concerns regarding changes in bone resorption markers. A combination of the loading treatment with a subsequent maintenance dose of 2000 IU daily is adequate to achieve the target vitamin D levels. Full article
(This article belongs to the Special Issue Drug Insights: Vitamin D and Its Analogs 2023)
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11 pages, 252 KiB  
Article
A Therapeutic Proposal for Mini-Puberty in Male Infants with Hypogonadotropic Hypogonadism: A Retrospective Case Series
by María Aurora Mesas-Aróstegui, Fidel Hita-Contreras and Juan Pedro López-Siguero
J. Clin. Med. 2024, 13(22), 6983; https://doi.org/10.3390/jcm13226983 - 20 Nov 2024
Cited by 1 | Viewed by 1327
Abstract
Background: Male patients with congenital hypogonadotropic hypogonadism (CHH) have impaired postnatal activation of the hypothalamic–pituitary–gonadal axis that occurs during mini-puberty. The aim of this study was to report our experience using gonadotropin replacement therapy for mini-puberty in male infants with CHH and to [...] Read more.
Background: Male patients with congenital hypogonadotropic hypogonadism (CHH) have impaired postnatal activation of the hypothalamic–pituitary–gonadal axis that occurs during mini-puberty. The aim of this study was to report our experience using gonadotropin replacement therapy for mini-puberty in male infants with CHH and to establish treatment recommendations. Methods: The patients included in this retrospective case series (n = 9) were diagnosed in the postnatal period due to micropenis, with two being accompanied by cryptorchidism and four with other associated hormonal deficits. All patients started treatment with gonadotropins early after diagnosis, between 2 weeks and 5 months of age, with a schedule of discontinuous injections with subcutaneous human chorionic gonadotropin (62.5–500 IU) two times per week and recombinant follicle-stimulating hormone-alpha (37.5–75 IU) three times per week. Results: The data from our study show an early response, ranging from almost undetectable levels of testosterone at diagnosis to elevated levels after starting treatment, as well as a positive clinical response with increases in testicular volume and penis size in all cases without requiring complementary treatment with testosterone esters and without adverse effects. Conclusions: Our results show that gonadotropin replacement therapy is a well-tolerated and effective treatment for testicular and penile problems in male patients with CHH. Full article
(This article belongs to the Special Issue Current Trends in Pediatric Endocrinology)
15 pages, 290 KiB  
Review
Daily and Weekly “High Doses” of Cholecalciferol for the Prevention and Treatment of Vitamin D Deficiency for Obese or Multi-Morbidity and Multi-Treatment Patients Requiring Multi-Drugs—A Narrative Review
by Pawel Pludowski, Ewa Marcinowska-Suchowierska, Galymzhan Togizbayev, Zhanna Belaya, William B. Grant, Stefan Pilz and Michael F. Holick
Nutrients 2024, 16(15), 2541; https://doi.org/10.3390/nu16152541 - 3 Aug 2024
Cited by 6 | Viewed by 6530
Abstract
Daily vitamin D supplementation using higher than normal dosing (up to the upper limit value) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database, a thorough search for published [...] Read more.
Daily vitamin D supplementation using higher than normal dosing (up to the upper limit value) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database, a thorough search for published randomized controlled trials and other studies was conducted, and the results were analyzed. This review provides an overview of the use of 7000 IU daily, 30,000 IU per week or twice weekly, and 50,000 IU weekly of vitamin D for obtaining and maintaining 25(OH)D concentrations of at least 30 ng/mL in patients at high risk of vitamin D deficiency. The abovementioned dosages should be considered in adults with obesity, liver disease or malabsorption syndromes, or multi-diseased patients, mainly seniors requiring multi-drug treatment, including drugs affecting vitamin D metabolism. The simple schedules of 7000 IU/day, 30,000 IU/week or twice weekly, and 50,000 IU/week for use by patients with an increased risk of vitamin D deficiency were provided for consideration. Without monitoring of 25(OH)D, daily doses of 7000 IU or intermittent doses of 30,000 IU/week should be considered for a prolonged time as prophylactic or maintenance doses, mainly in obese patients, patients with liver disease and patients with malabsorption syndromes. For the treatment of possible vitamin D deficiency without assessment of 25(OH)D in these groups, intermittent doses of 30,000 IU twice weekly or 50,000 IU per week should be considered for a 6–8-week period only. The higher daily doses or the intermittent doses suggested above are effective, safe and responsive based on patient’s preferences. Full article
15 pages, 1678 KiB  
Article
Dietary 25-Hydroxycholecalciferol Supplementation as a Vitamin D3 Substitute Improves Performance, Egg Quality, Blood Indexes, Jejunal Morphology, and Tibia Quality in Late-Phase Laying Hens
by Shan Gao, Kai Qiu, Junjie Zheng, Haijun Zhang, Jing Wang, Xiaolong Qi and Shugeng Wu
Animals 2024, 14(6), 878; https://doi.org/10.3390/ani14060878 - 13 Mar 2024
Cited by 9 | Viewed by 2848
Abstract
This study aimed to investigate whether a dietary 25-OHD3 addition improved the performance, egg quality, blood indexes, antioxidant status, jejunal morphology, and tibia quality of aged laying hens compared to a dietary VD3 addition. A total of 270 Hy-Line Brown laying [...] Read more.
This study aimed to investigate whether a dietary 25-OHD3 addition improved the performance, egg quality, blood indexes, antioxidant status, jejunal morphology, and tibia quality of aged laying hens compared to a dietary VD3 addition. A total of 270 Hy-Line Brown laying hens at 55 wk of age were randomly assigned to three dietary treatments with six replicates (15 birds per replicate with 3 birds per cage). Chickens were fed a corn–soybean meal diet supplementation of 4000 IU/kg VD3 (control group), 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 (experimental group 1), or 50 μg/kg 25-OHD3 and 4000 IU/kg VD3 (experimental group 2) for 12 weeks. The results demonstrated that 25-OHD3 caused a significant increase in the laying rate, especially in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group; the laying rate reached the maximum compared with other groups after 12 weeks (p < 0.05). However, there were no significant effects on the average egg weight, average daily feed intake, or feed-to-egg ratio (p > 0.05). A dietary supplementation of 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 provided an improved eggshell strength, thick albumen height, and Haugh unit after 12 weeks (p < 0.05). Further analysis of the blood indexes showed that alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, calcium, and phosphorus were enhanced significantly in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group, while the content of total bilirubin decreased significantly (p < 0.05). In addition, the 25-OHD3 addition in diets improved the calcium and phosphorus contents in the serum (p < 0.05). The concentrations of 25-OHD3, parathyroid hormones, follicle-stimulating hormone, and progesterone were increased in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group, and the levels of cortisol, calcitonin, bone gla protein, and endotoxin in the serum reached a minimum in the 50 μg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05), which constitutes an advantage for the aged laying hens. The antioxidant enzyme activities and free radical scavenging abilities in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group increased markedly, and the MDA level decreased significantly in the 50 μg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05). Improvements in jejunal morphology and intestinal integrity resulted in an increased villi-length-to-crypt-depth ratio in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group (p < 0.05). Dietary 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 additions improved the tibia quality, including fresh tibia weight, strength, mineral content (Ca), and trabeculae area (p < 0.05). Taken together, compared with the dietary VD3 addition, dietary supplementation of 25-OHD3 supported a stable physiological status for sustained egg production, egg quality, and bone quality in late-phase laying hens, and the addition levels of 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 had the best effect. Therefore, this could provide a theoretical basis for the use of 25-OHD3 as a substitute forVD3. Full article
(This article belongs to the Collection Poultry Nutrition and Metabolism)
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18 pages, 2719 KiB  
Article
Retreatment with HBV siRNA Results in Additional Reduction in HBV Antigenemia and Immune Stimulation in the AAV-HBV Mouse Model
by Ellen Van Gulck, Nádia Conceição-Neto, Liese Aerts, Wim Pierson, Lore Verschueren, Mara Vleeschouwer, Vinod Krishna, Isabel Nájera and Frederik Pauwels
Viruses 2024, 16(3), 347; https://doi.org/10.3390/v16030347 - 23 Feb 2024
Cited by 2 | Viewed by 2908
Abstract
Background and Aims: Treatment with siRNAs that target HBV has demonstrated robust declines in HBV antigens. This effect is also observed in the AAV-HBV mouse model, which was used to investigate if two cycles of GalNAc-HBV-siRNA treatment could induce deeper declines in HBsAg [...] Read more.
Background and Aims: Treatment with siRNAs that target HBV has demonstrated robust declines in HBV antigens. This effect is also observed in the AAV-HBV mouse model, which was used to investigate if two cycles of GalNAc-HBV-siRNA treatment could induce deeper declines in HBsAg levels or prevent rebound, and to provide insights into the liver immune microenvironment. Methods: C57Bl/6 mice were transduced with one of two different titers of AAV-HBV for 28 days, resulting in stable levels of HBsAg of about 103 or 105 IU/mL. Mice were treated for 12 weeks (four doses q3wk) per cycle with 3 mg/kg of siRNA-targeting HBV or an irrelevant sequence either once (single treatment) or twice (retreatment) with an 8-week treatment pause in between. Blood was collected to evaluate viral parameters. Nine weeks after the last treatment, liver samples were collected to perform phenotyping, bulk RNA-sequencing, and immunohistochemistry. Results: Independent of HBsAg baseline levels, treatment with HBV-siRNA induced a rapid decline in HBsAg levels, which then plateaued before gradually rebounding 12 weeks after treatment stopped. A second cycle of HBV-siRNA treatment induced a further decline in HBsAg levels in serum and the liver, reaching undetectable levels and preventing rebound when baseline levels were 103 IU/mL. This was accompanied with a significant increase in inflammatory macrophages in the liver and significant upregulation of regulatory T-cells and T-cells expressing immune checkpoint receptors. Conclusions: Retreatment induced an additional decline in HBsAg levels, reaching undetectable levels when baseline HBsAg levels were 3log10 or less. This correlated with T-cell activation and upregulation of Trem2. Full article
(This article belongs to the Special Issue Recent Advances in Anti-HCV, Anti-HBV and Anti-flavivirus Agents)
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19 pages, 4319 KiB  
Article
Sex Differences under Vitamin D Supplementation in an Animal Model of Progressive Multiple Sclerosis
by Michaela Tanja Haindl, Muammer Üçal, Cansu Tafrali, Willibald Wonisch, Cigdem Erdogan, Marta Nowakowska, Milena Z. Adzemovic, Christian Enzinger, Michael Khalil and Sonja Hochmeister
Nutrients 2024, 16(4), 554; https://doi.org/10.3390/nu16040554 - 17 Feb 2024
Cited by 1 | Viewed by 4963
Abstract
A central role for vitamin D (VD) in immune modulation has recently been recognized linking VD insufficiency to autoimmune disorders that commonly exhibit sex-associated differences. Similar to other autoimmune diseases, there is a higher incidence of multiple sclerosis (MS) in women, but a [...] Read more.
A central role for vitamin D (VD) in immune modulation has recently been recognized linking VD insufficiency to autoimmune disorders that commonly exhibit sex-associated differences. Similar to other autoimmune diseases, there is a higher incidence of multiple sclerosis (MS) in women, but a poorer prognosis in men, often characterized by a more rapid progression. Although sex hormones are most likely involved, this phenomenon is still poorly understood. Oxidative stress, modulated by VD serum levels as well as sex hormones, may act as a contributing factor to demyelination and axonal damage in both MS and the corresponding preclinical models. In this study, we analyzed sex-associated differences and VD effects utilizing an animal model that recapitulates histopathological features of the progressive MS phase (PMS). In contrast to relapsing–remitting MS (RRMS), PMS has been poorly investigated in this context. Male (n = 50) and female (n = 46) Dark Agouti rats received either VD (400 IU per week; VD+) or standard rodent food without extra VD (VD) from weaning onwards. Myelination, microglial activation, apoptotic cell death and neuronal viability were assessed using immunohistochemical markers in brain tissue. Additionally, we also used two different histological markers against oxidized lipids along with colorimetric methods to measure protective polyphenols (PP) and total antioxidative capacity (TAC) in serum. Neurofilament light chain serum levels (sNfL) were analyzed using single-molecule array (SIMOA) analysis. We found significant differences between female and male animals. Female rats exhibited a better TAC and higher amounts of PP. Additionally, females showed higher myelin preservation, lower microglial activation and better neuronal survival while showing more apoptotic cells than male rats. We even found a delay in reaching the peak of the disease in females. Overall, both sexes benefitted from VD supplementation, represented by significantly less cortical, neuroaxonal and oxidative damage. Unexpectedly, male rats had an even higher overall benefit, most likely due to differences in oxidative capacity and defense systems. Full article
(This article belongs to the Special Issue Vitamin D, Immune Response, and Autoimmune Diseases)
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12 pages, 273 KiB  
Article
Dynamic Evaluation of Vitamin D Metabolism in Post-Bariatric Patients
by Alexandra Povaliaeva, Artem Zhukov, Alina Tomilova, Axenia Bondarenko, Maksim Ovcharov, Mariya Antsupova, Vitaliy Ioutsi, Ekaterina Shestakova, Marina Shestakova, Ekaterina Pigarova, Liudmila Rozhinskaya and Natalia Mokrysheva
J. Clin. Med. 2024, 13(1), 7; https://doi.org/10.3390/jcm13010007 - 19 Dec 2023
Cited by 1 | Viewed by 1872
Abstract
Background: findings from the previously conducted studies indicate altered regulatory mechanisms of calcium and vitamin D metabolism in obese patients and a role for bariatric surgery in regulating vitamin D metabolism; however, the available data is controversial and does not provide an adequate [...] Read more.
Background: findings from the previously conducted studies indicate altered regulatory mechanisms of calcium and vitamin D metabolism in obese patients and a role for bariatric surgery in regulating vitamin D metabolism; however, the available data is controversial and does not provide an adequate understanding of the subject. Methods: we evaluated serum parameters of vitamin D and mineral metabolism (vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3), vitamin D-binding protein (DBP), free 25(OH)D, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), total calcium, albumin, phosphorus, creatinine, magnesium) in 30 patients referred for bariatric surgery in comparison with 30 healthy volunteers of similar age, sex and baseline 25(OH)D3. Patients were also followed up with repeated laboratory assessments 3 months and 6 months after surgery. During the first 3 months, patients were prescribed high-dose cholecalciferol therapy (50,000 IU per week), with subsequent correction based on the results of the 3-month visit examination. Results: Preoperatively, patients with morbid obesity were characterized by a high prevalence of vitamin D deficiency (median 25(OH)D3 level 11.9 (6.8; 22.2) ng/mL), significantly lower levels of active vitamin D metabolite 1,25(OH)2D3 (20 (10; 37) vs. 39 (33; 50) pg/mL, p < 0.001), lower serum albumin-adjusted calcium levels (2.24 (2.20; 2.32) vs. 2.31 (2.25; 2.35) mmol/L, p = 0.009) and magnesium levels (0.79 (0.72; 0.82) vs. 0.82 (0.78; 0.85) mmol/L, p = 0.043) with simultaneous similar PTH levels (p = 0.912), and higher DBP levels (328 (288; 401) vs. 248 (217; 284) mg/L, p < 0.001). The 25(OH)D3 levels remained suboptimal (24.5 (14.7; 29.5) ng/mL at the 3-month visit and 17.9 (12.4; 21.0) ng/mL at the 6-month visit, p = 0.052) despite recommended high-dose cholecalciferol supplementation. Patients also demonstrated an increase in 1,25(OH)2D3 levels (38 (31; 52) pg/mL at the 3-month visit and 49 (29; 59) pg/mL at the 6-month visit, p < 0.001) without a change in PTH or calcium levels during the follow-up. Conclusion: our results of a comprehensive laboratory evaluation of vitamin D status and mineral metabolism in patients undergoing bariatric surgery highlight the importance of improving current clinical guidelines, as well as careful monitoring and education of patients. Full article
(This article belongs to the Special Issue Clinical Advances in Obesity and Bariatric Surgery)
17 pages, 3787 KiB  
Article
A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID
by Tom Wai-Hin Chung, Hui Zhang, Fergus Kai-Chuen Wong, Siddharth Sridhar, Tatia Mei-Chun Lee, Gilberto Ka-Kit Leung, Koon-Ho Chan, Kui-Kai Lau, Anthony Raymond Tam, Deborah Tip-Yin Ho, Vincent Chi-Chung Cheng, Kwok-Yung Yuen, Ivan Fan-Ngai Hung and Henry Ka-Fung Mak
Brain Sci. 2023, 13(7), 1014; https://doi.org/10.3390/brainsci13071014 - 30 Jun 2023
Cited by 8 | Viewed by 3500
Abstract
Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral [...] Read more.
Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs–fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127–175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs–fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID. Full article
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14 pages, 3140 KiB  
Article
Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren’s Syndrome
by Maria Consiglia Trotta, Hildegard Herman, Cornel Balta, Marcel Rosu, Alina Ciceu, Bianca Mladin, Carlo Gesualdo, Caterina Claudia Lepre, Marina Russo, Francesco Petrillo, Gorizio Pieretti, Francesca Simonelli, Settimio Rossi, Michele D’Amico and Anca Hermenean
Biomedicines 2023, 11(2), 616; https://doi.org/10.3390/biomedicines11020616 - 18 Feb 2023
Cited by 5 | Viewed by 2797
Abstract
Background: Vitamin D deficiency has been associated with dry eye development during Sjögren’s syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin [...] Read more.
Background: Vitamin D deficiency has been associated with dry eye development during Sjögren’s syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C−) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). Results: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C−), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. Conclusions: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye. Full article
(This article belongs to the Special Issue Recent Advances in Vitamin D)
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12 pages, 1023 KiB  
Article
Effects of Supplementation of 25-Hydroxyvitamin D3 as a Vitamin D3 Substitute on Performance, Bone Traits, and Egg Quality of Laying Hens from 1 Day to 72 Weeks of Age
by Dongdong Li, Xuemei Ding, Shiping Bai, Jianping Wang, Qiufeng Zeng, Huanwei Peng, Yue Xuan and Keying Zhang
Agriculture 2023, 13(2), 383; https://doi.org/10.3390/agriculture13020383 - 6 Feb 2023
Cited by 5 | Viewed by 3546
Abstract
This experiment was conducted to explore the effect of long-term supplementation of 25-hydroxyvitamin D3 (25-OHD) as a vitamin D3 (VD3) substitute on performance, bone traits, and egg quality of laying hens from 1 day to 72 weeks of age. [...] Read more.
This experiment was conducted to explore the effect of long-term supplementation of 25-hydroxyvitamin D3 (25-OHD) as a vitamin D3 (VD3) substitute on performance, bone traits, and egg quality of laying hens from 1 day to 72 weeks of age. In total, 900 one-day-old Lohman pullets were randomly allotted into three dietary groups (three treatments × 15 replicates × 20 birds per replicate): VD3 2800 IU/kg; 25-OHD 69 μg/kg; 25-OHD 125 μg/kg. At the end of the 20th w, five replicates from each group were selected to feed on the same vitamin D diets, as used during the rearing stage (1–20 w) until 72 w. The result showed that the 25-OHD 125 μg/kg treatment had the lowest average daily feed intake (ADFI) at 1–8 or 1–19 w, body weight at 8 w, body weight gain between 1 and 8 w and shank length at 4 w (p < 0.05). The 25-OHD 125 μg/kg treatment had a lower shank length at 7 w, compared with the 25-OHD 69 μg/kg treatment. The shank length of the birds in each treatment reached the maximum (about 103 mm) at about 18 w of age. For the bone traits, the 25-OHD 125 μg/kg treatment had the lowest femur bone diameter at 20 w (p < 0.001) and femur bone plumpness at 20 w (p = 0.002). The 25-OHD 125 μg/kg treatment had a lower tibia strength at 10 w (p = 0.023) and keel length at 10 w (p = 0.046), compared with the 25-OHD 69 μg/kg treatment. However, both 25-OHD 69 and 125 μg/kg treatments had a greater femur strength at 72 w (p = 0.006), compared with the VD3 2800 IU/kg treatment. No difference in laying performance was observed among all treatments. The overall (21–72 w) ADFI in the 25-OHD 125 μg/kg treatment was significantly lower than that in the 25-OHD 69 μg/kg treatment (p = 0.030). At 60 w, the 25-OHD 125 μg/kg treatment had a lower eggshell thickness (p = 0.012) and proportion of eggshell (p = 0.022), compared with the 25-OHD 69 μg/kg treatment. No significant differences in egg quality parameters were observed at 50 and 70 w among treatments. In general, supplementary 2800 IU/kg doses of VD3 at the early stage were sufficient to maintain the bone quality and growth and development of pullets. Feeding birds at a higher 25-OHD level (125 μg/kg) resulted in the reduced ADFI and growth at the rearing period, but the long-term supplementation of 25-OHD as a VD3 substitute improved the bone quality in the late laying period. Full article
(This article belongs to the Special Issue Animal Nutrition and Productions: Series II)
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14 pages, 5666 KiB  
Article
Vitamin D Ameliorates the Hepatic Oxidative Damage and Fibrotic Effect Caused by Thioacetamide in Rats
by Aya Megahed, Hossam Gadalla, Fatma M. Abdelhamid, Samah J. Almehmadi, Anmar A. Khan, Talat A. Albukhari and Engy F. Risha
Biomedicines 2023, 11(2), 424; https://doi.org/10.3390/biomedicines11020424 - 1 Feb 2023
Cited by 12 | Viewed by 3235
Abstract
Vitamin D3 (VD3) is a sunshine hormone that regulates cellular proliferation, differentiation, apoptosis, and angiogenesis related to liver parenchyma. We used a thioacetamide (TAA)-induced hepatic fibrosis rat model in our study to investigate the beneficial roles of VD3 to [...] Read more.
Vitamin D3 (VD3) is a sunshine hormone that regulates cellular proliferation, differentiation, apoptosis, and angiogenesis related to liver parenchyma. We used a thioacetamide (TAA)-induced hepatic fibrosis rat model in our study to investigate the beneficial roles of VD3 to overcome extensive liver fibrosis. Randomly, four equal groups (eight rats per group) underwent therapy for eight successive weeks: a control group, a group treated with TAA 100 mg/kg BW IP every other day, a group treated with VD3 1000 IU/kg BW IM every day, and a TAA+VD group treated with both therapies. Treatment with VD3 after TAA-induced hepatic fibrosis was found to alleviate elevated liver function measures by decreasing ALT, AST, and ALP activity; decreasing total bilirubin, direct bilirubin, cholesterol, and triglyceride levels; and increasing glucose and 25[OH]D3. Rats treated with VD3 showed marked decreases in MDA and increased SOD, CAT, and GSH levels. In addition, CD34 and FGF23 gene expressions were reduced after dual therapy. Liver sections from the TAA+VD group showed markedly decreased hepatic lesions, and Masson’s trichrome stain showed a marked decrease in dense bluish-stained fibrous tissue. The immunohistochemical expression of TGF-β and α-SMA showed markedly decreased positive brown cytoplasmic expression in a few hepatocytes, clarifying the antifibrotic effect of VD3 in hepatic fibrosis. In conclusion, VD3 alleviates hepatotoxicity and fibrosis caused by TAA. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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12 pages, 2411 KiB  
Article
Sexual and Reproductive Outcomes in Obese Fertile Men with Functional Hypogonadism after Treatment with Liraglutide: Preliminary Results
by Sandro La Vignera, Rosita A. Condorelli, Aldo E. Calogero, Rossella Cannarella and Antonio Aversa
J. Clin. Med. 2023, 12(2), 672; https://doi.org/10.3390/jcm12020672 - 14 Jan 2023
Cited by 30 | Viewed by 8602
Abstract
Purpose: To prospectively investigate the effects of treatment with liraglutide, a glucagon-like peptide 1 (GLP1) analog, on reproductive and sexual function in men with metabolic hypogonadism who are of childbearing age. Materials and Methods: To accomplish this purpose, 110 men of [...] Read more.
Purpose: To prospectively investigate the effects of treatment with liraglutide, a glucagon-like peptide 1 (GLP1) analog, on reproductive and sexual function in men with metabolic hypogonadism who are of childbearing age. Materials and Methods: To accomplish this purpose, 110 men of childbearing age (18–35 years) with metabolic hypogonadism were enrolled and divided into three groups, according to their desire to have children. Group A was made up of men actively seeking fatherhood, Group B, of men who did not seek fatherhood, and Group C, of men who had already fathered a child. Group A patients were treated with gonadotropins (urofollitropin at 150 IU, three times a week, and human chorionic gonadotropin at 2000 IU, twice a week), Group B patients with liraglutide (3 mg daily), and Group C patients with transdermal testosterone (60 mg per day). All patients were treated for 4 months. Results: Patients treated with liraglutide (Group B) showed significant improvement in conventional sperm parameters, compared to baseline and Group A patients, and in the quality of erectile function compared to baseline and patients of Groups A and C. In addition, they had significantly higher levels of total testosterone and sex hormone-binding globulin serum levels after 4 months of treatment with liraglutide than those achieved by patients in the other two groups at the end of the respective treatments. Finally, Group B patients also showed significantly higher serum gonadotropin levels than the other groups. Conclusions: The results of this study showed, for the first time, the efficacy of liraglutide, a GLP1 analog, for the pharmacological treatment of male patients with metabolic hypogonadism. Liraglutide has also shown advantages over traditional treatments on both reproductive and sexual function and appears to offer greater benefits in terms of metabolic protection. These findings suggest that liraglutide is a useful drug for the treatment of obese males with metabolic hypogonadism. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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16 pages, 1885 KiB  
Article
Small-Scale Randomized Controlled Trial to Explore the Impact of β-Hydroxy-β-Methylbutyrate Plus Vitamin D3 on Skeletal Muscle Health in Middle Aged Women
by William D. Fairfield, Dennis M. Minton, Christian J. Elliehausen, Alexander D. Nichol, Taylor L. Cook, John A. Rathmacher, Lisa M. Pitchford, Scott A. Paluska, Adam J. Kuchnia, Jacob M. Allen and Adam R. Konopka
Nutrients 2022, 14(21), 4674; https://doi.org/10.3390/nu14214674 - 4 Nov 2022
Cited by 6 | Viewed by 6800
Abstract
β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function. However, HMB may be less effective at improving muscle function in people with insufficient Vitamin D3 (25-OH-D < 30 ng/mL) which is common in middle-aged and older [...] Read more.
β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function. However, HMB may be less effective at improving muscle function in people with insufficient Vitamin D3 (25-OH-D < 30 ng/mL) which is common in middle-aged and older adults. Therefore, we tested the hypothesis that combining HMB plus Vitamin D3 (HMB + D) supplementation would improve skeletal muscle size, composition, and function in middle-aged women. In a double-blinded fashion, women (53 ± 1 yrs, 26 ± 1 kg/m2, n = 43) were randomized to take placebo or HMB + D (3 g Calcium HMB + 2000 IU D per day) during 12 weeks of sedentary behavior (SED) or resistance exercise training (RET). On average, participants entered the study Vitamin D3 insufficient while HMB + D increased 25-OH-D to sufficient levels after 8 and 12 weeks. In SED, HMB + D prevented the loss of arm lean mass observed with placebo. HMB + D increased muscle volume and decreased intermuscular adipose tissue (IMAT) volume in the thigh compared to placebo but did not change muscle function. In RET, 12-weeks of HMB + D decreased IMAT compared to placebo but did not influence the increase in skeletal muscle volume or function. In summary, HMB + D decreased IMAT independent of exercise status and may prevent the loss or increase muscle size in a small cohort of sedentary middle-aged women. These results lend support to conduct a longer duration study with greater sample size to determine the validity of the observed positive effects of HMB + D on IMAT and skeletal muscle in a small cohort of middle-aged women. Full article
(This article belongs to the Special Issue The Impact of Nutritional Strategies on Muscle Health)
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12 pages, 791 KiB  
Article
Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial
by Sophie De Niet, Mickaël Trémège, Monte Coffiner, Anne-Francoise Rousseau, Doriane Calmes, Anne-Noelle Frix, Fanny Gester, Muriel Delvaux, Anne-Francoise Dive, Elora Guglielmi, Monique Henket, Alicia Staderoli, Didier Maesen, Renaud Louis, Julien Guiot and Etienne Cavalier
Nutrients 2022, 14(15), 3048; https://doi.org/10.3390/nu14153048 - 26 Jul 2022
Cited by 60 | Viewed by 23500
Abstract
Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length [...] Read more.
Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D. Full article
(This article belongs to the Section Micronutrients and Human Health)
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