Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice.

Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-γ, TNF-α, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients.

Type 1 Plasminogen Deficiency With Pulmonary Involvement: Novel Treatment and Novel Mutation.

Type 1 plasminogen deficiency is a rare genetic disorder. Type 1 plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on mucosal surfaces, particularly the conjunctiva. Tracheobronchial tree involvement is a less common reported manifestation of type 1 plasminogen deficiency. Pseudomembranes in the tracheobronchial tree may result in respiratory compromise and ultimately fail if not recognized and treated. Currently, there is no specific replacement therapy approved for the treatment of congenital plasminogen deficiency. In the present paper, we report that type 1 plasminogen deficiency with novel frameshift mutation and pulmonary involvement was treated initially with systemic fresh frozen plasma followed by pulmonary lavage with fresh frozen plasma and tissue plasminogen activator.

The efficacy of vitamin K2 and calcitriol combination on thalassemic osteopathy.

Thalassemic osteopathy (TOSP) has emerged as a topic of interest, as the optimized transfusion regimens and iron chelations has markedly improved the survival of the patients suffering from thalassemia major (TM) and increased the life expectancy. The aim of this prospective monocentric pilot study was to investigate the effects of a dietary supplement with vitamin K2 (50 mcg menaquinone-7) and vitamin D (5 mcg calcitriol) on the patients with TOSP. Twenty children (12 girls, 8 boys; age varied from 3 to 18 y) with ß TM, who underwent regular blood transfusion and iron chelation therapy, were enrolled in this study and investigated at the initial, sixth, and 12th month of the treatment. We detected a significant improvement in the bone mineral density and Z-score at the lumbar spine area of the patients at the sixth and 12th month of the treatment, especially in the prepubertal group. We also found a decrease in the ratio of undercarboxylated osteocalcin to carboxylated osteocalcin, however, this was not found to be significant. Although the natural course of TOSP is worsening or at least stabilizing, our pilot study demonstrated that vitamin K2 and calcitriol combination clearly has a positive effect on the bone mineral density of the children with TM during a 1-year period. Supplementation of menaquinone-7 instead of drugs is an augmented physiological intake and seems a beneficial alternative for the treatment of TOSP. Further studies on a large number of participants are necessary to highlight the effect of vitamin K2 on TOSP.

The effect of bovine colostrum on viral upper respiratory tract infections in children with immunoglobulin A deficiency.

INTRODUCTION: Immunoglobulin A (IgA)-deficient patients predominantly suffer from respiratory and gastrointestinal infections since secretory IgA has important functions to protect mucosal surfaces. OBJECTIVE: To evaluate the effect of bovine colostrum, rich in IgA, on the treatment of viral upper respiratory tract (URT) infections in IgA-deficient children. METHODS: Thirty-one IgA-deficient children with viral URT infections were included in this double-blind, placebo-controlled study, and randomly oral bovine colostrum or placebo was given three times a day for 1 week. Samples of saliva IgA were collected before treatment, after the administration of the first dose, and after the last dose. Mothers of the children completed a daily questionnaire regarding the severity of the infection and any adverse effects. RESULTS: The bovine colostrum group had a lower infection severity score than the placebo group after 1 week (respectively 0.81±0.83, 3.00±1.85; P=0.000), but there was no difference between the salivary IgA levels of the groups. CONCLUSION: This is the first study to evaluate the effect of bovine colostrum in IgA-deficient children, and no adverse effects were observed. However, further studies are needed to confirm the efficacy and safety of bovine colostrum in IgA-deficient patients.

The efficacy of Pelargonium sidoides in the treatment of upper respiratory tract infections in children with transient hypogammaglobulinemia of infancy.

Transient hypogammaglobulinemia of infancy (THI), defined as prolongation of physiological hypogammaglobulinemia normally seen between the initial 3rd and 6th months of life, is one of the most common immune deficiencies of childhood. Recurrent upper respiratory tract infections (URTI) are rather common in this group of patients, and generally, antibiotic treatment is the usual choice, although viruses involved in most cases. Pelargonium sidoides extract a herbal drug with known immunmodulator, antiviral and antibacterial effects. In this randomized, placebo controlled, prospective, monocentric pilot study, 14 of 28 patients with a diagnosed THI, were given Pelargonium sidoides, while 14 were given placebo during the period of URTI. Before and after the treatment period of one week, complete blood count, prothrombin time, activated prothromboplastin time, serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, total and direct bilirubin levels were measured. Mothers were asked to fill in a questionnaire for the recovery of the clinical symptoms during the treatment. The results were evaluated and compared in both group to assess the effect of Pelargonium sidoides. As a conclusion, the Pelargonium sidoides group showed increased appetite. The Pelargonium sidoides were found to beneficial for the nasal congestion, recovery of daily and nocturnal cough but not found be significant. Further studies with large number of participants are necessary to highlight the effect of Pelargonium sidoides in children with transient hypogammaglobulinemia of infancy.

Coenzyme Q10 levels in ß-thalassemia and its association with ferritin levels and chelation therapy.

The aim of this study was to evaluate the plasma coenzyme Q(10) (CoQ(10)) concentration, a vitamin-like substance found in every cell, which is also viewed as the most effective membrane antioxidant, of thalassemic patients and investigate the effect of chelating agents and ferritin levels on its concentration in patients with ß-thalassemia major (ß-TM). The study included 44 ß-TM patients undergoing deferasirox (DFRA) or deferoxamine (DFO) chelation monotherapies or combined therapy with deferiprone (L1) and DFO, 20 patients with ß-thalassemia (ß-thal) traits and a control group of 22 healthy sex- and age-matched subjects. Complete blood counts, liver and renal function tests, lipid profiles, ferritin and plasma CoQ(10) [by high performance liquid chromatography (HPLC)] were analyzed. The mean age (14.7 ± 7.3 years; median 14.3 years) and sex (26 males, 18 females) of the ß-TM patients were not statistically different from the ß-thal trait patients and the control group. The plasma CoQ(10) concentration was 0.425 ± 0.136 µmol/L in ß-TM patients, 0.508 ± 0.159 µmol/L in the ß-thal trait patients and 0.534 ± 0.133 µmol/L in the control group. The difference was significant in both the ß-TM (p < 0.001) and ß-thal trait patients (p <0.05) compared to the control group. The CoQ(10) concentration was also associated with ferritin levels in ß-TM patients; the ß-TM patients with high ferritin levels had a lower CoQ(10) (p <0.05) concentration. Also, higher plasma CoQ(10) levels were detected in ß-TM patients undergoing DFRA treatment, according to combined therapy administered (0.457 ± 0.115 vs. 0.382 ± 0.127 mg/dL respectively, p <0.05). In conclusion, both the ß-thal trait and ß-TM patients have lower antioxidant capacity as demonstrated by the lower CoQ(10) levels. The type of chelating agents and ferritin levels are factors effecting CoQ(10) concentration in ß-TM patients.

Treatment of thalassemia-induced osteoporosis with intermittent pamidronate infusions: Two-year follow up.

OBJECTIVE: The purpose of this study was to evaluate the bone mineral density (BMD) in 23 patients aged 7-14 years with thalassemia major and to assess the alterations in bone density in a two-year follow-up study. METHOD: BMD of the lumbar spine and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) at baseline, after 12 months of treatment and two years later. Pamidronate treatment (15 mg/dose, every 3 months for 1 year) was given to 23 osteoporotic (Z score below -2.5) and osteopenic (Z score -1 to -2.5) patients. After 12 months of treatment, all patients received only calcium and vitamin D supplements. After the two years of follow-up, BMD of the lumbar spine and femur was measured using DXA. RESULT: Administration of pamidronate resulted in a significant increase in BMD of the femoral neck. Lumbar spine BMD after pamidronate treatment was slightly higher than at baseline, but this was statistically non-significant. After two years, femoral neck and lumbar BMD had significantly increased compared to baseline. CONCLUSION: In view of the present findings, longer follow-up studies to determine long-term treatment are fully warranted.