Effect of azithromycin on bronchiolitis obliterans syndrome in posttransplant recipients: A systematic review and meta-analysis.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a devastating complication that occurs after transplantation. Although azithromycin is currently used for the treatment of BOS, the evidence is sparse and controversial. The aim of this meta-analysis is to evaluate the effects of azithromycin on forced expiratory volume in 1 second (FEV1) and patient's survival. METHODS: PubMed, Embase, Cochrane library, Web of Science databases, and the ClinicalTrials.gov registry were systematically searched from inception until December 2020 for relevant original research articles. Random-effects models were used to calculate pooled-effect estimates. RESULTS: Searches identified 15 eligible studies involving 694 participants. For FEV1 (L), there was a significant increase after short-term (≤12 weeks; P = .00) and mid-term (12-24 weeks; P = .01) administration of azithromycin. For FEV1 (%) compared to baseline, there was a significant increase after short-term (≤12 weeks) administration of azithromycin (P = .02), while there were no statistically significant differences in the medium and long term. When pooled FEV1% was predicted, it exhibited a similar trend to FEV1 (%) compared to baseline. In addition, we discovered that azithromycin reduced the risk of death (hazard ratio = 0.26; 95% confidence interval = 0.17 to 0.40; P = .00) in patients with BOS post-lung transplantation. CONCLUSIONS: Azithromycin therapy is both effective and safe for lung function improvement in patients with posttransplant BOS after the short- and medium-term administration. Additionally, it has been demonstrated a significant survival benefit among patients with BOS post-lung transplant. Higher quality randomized controlled trials and more extensive prospective cohort studies are needed to confirm the effect of azithromycin on patients with posttransplant BOS.

Melanoma therapy with transdermal mitoxantrone cubic phases.

CONTEXT: Melanoma therapy absorbs attention because of the high morbidity and mortality. However, currently systematic administrations could take little therapeutic efficiency and severe side effects. OBJECTIVE: An effective transdermal formulation for the convenient melanoma therapy was found and evaluated. MATERIALS AND METHODS: A mitoxantrone (MTO) cubic phase was prepared with glyceryl monooleate, ethanol and water. The permeation, cytotoxicity, in vivo anti-melanoma effect of the MTO cubic phases were evaluated. The anti-cancer mechanism of the MTO cubic phases was explored according to the immunohistochemistry and flow cytometry. RESULTS AND DISCUSSION: The isotropic structure of MTO cubic phases was identified. The transdermal permeability of MTO was greatly improved by the cubic phase compared to that of the MTO solution. The MTO cubic phases showed the high cytotoxicity in B16 melanoma cells evidenced by a modified electrical cell-substrate impedance sensing system. High anti-melanoma effect of the MTO cubic phases was confirmed according to the tumor volume changes and tumor weight. The tumor inhibitory rate of the MTO cubic phases was 68.44%. The calreticulin expression of B16 cells was improved by the MTO cubic phases, and the improved cell uptake of MTO was confirmed by the flow cytometry. CONCLUSION: The MTO cubic phase is a promising topical delivery system for melanoma therapy with the advantages of non-invasion and no severe side effects.

Improved anti-melanoma effect of a transdermal mitoxantrone ethosome gel.

Melanomas are malignant tumors characterized by early metastasis, rapid development, poor prognosis and high mortality. A highly effective and convenient method is necessary for long-term treatment of melanomas. Mitoxantrone (MTO) was topically applied for melanoma therapy using an MTO ethosome gel. Firstly, an ethosome was prepared from MTO, phospholipids, ethanol and water followed by addition of hydroxypropyl methylcellulose to obtain an ethosome gel. The ethosome was characterized. The cytotoxicity on B16 melanoma cells was evaluated on an electrical cell-substrate impedance sensing system with a novel modified chip. In vivo anti-melanoma effect of the ethosome gel was explored. Immunohistochemical and flow cytometric investigations were done. The MTO ethosomes had the size of 78nm and the zeta potential of -55mV. The ethosomes were flexible vesicles and showed much higher in vitro permeability across the rat skin than MTO aqueous solutions. The ethosomes had significant cytotoxicity and higher in vivo anti-melanoma effect than MTO solutions. The calreticulin membrane translocation of B16 cells was improved by the MTO ethosomes and the cell uptake of MTO was confirmed. The MTO ethosome gel is a promising transdermal delivery system for melanoma therapy with the advantages of non-invasion and no significant side effects.

Effect of simultaneous supplementation of vitamin A and iron on diarrheal and respiratory tract infection in preschool children in Chengdu City, China.

OBJECTIVE: The goal of this study was to investigate whether vitamin A combined with iron supplementation for preschool children resulted in improved changes in children's infectious morbidity. METHOD: In this randomized placebo-controlled and blinded field intervention trial, totally 445 preschoolers, ages 3 to 6 y old, were randomly selected. All children were randomly divided into four groups: vitamin A supplement-only group (group I), iron supplement-only group (group II), vitamin A and iron supplement group (group III), and no vitamin A and ferrous sulfate as placebo-control (group IV) for 6 mo. The morbidity of diarrhea and respiratory infections, were collected during supplementation. RESULTS: There was evidence of the lowest incidence rate of respiratory-related illnesses and fewest symptoms of runny nose, cough, and fever for children in group III compared with children in groups I, II and IV (P < 0.05). Moreover, despite the undistinguished incidence rate of vomiting, nausea, and stomach pain, the rate of diarrhea-related illness was significantly lower for children in group III than for those in the other three groups. CONCLUSION: The beneficial affects on infectious morbidity over 6 mo, highlight the potential of vitamin A plus an iron supplement for preschool-aged children.

[Preparation of transdermal drug delivery system of felodipine-metoprolol and its bioavailability in rabbits].

To prepare transdermal drug delivery system (TDDS) of felodipine and metoprolol and to study its pharmaceutical characteristics, pharmacokinetics and bioavailability in rabbits, an HPLC assay was established for the simultaneous determination of felodipine and metoprolol in the permeation receptor and patch. The permeation rate and permeation mechanism of felodipine-metoprolol-TDDS through rabbit skin in vitro was examined. The determination of drug content, the examination of content uniformity and stability of the TDDS were carried out. GC-ECD assays were established for the determination of felodipine and metoprolol in plasma separately and then employed to study the pharmacokinetics and bioavailability of felodipine and metoprolol after a single dose of oral or transdermal administration in rabbits. The results indicated that the permeation of flodipine and metoprolol from the patch through excised rabbit skin exhibited zero-order kinetic characteristics. The determination of drug content and the quality control of content uniformity of the patch accorded with Pharmacopoeia of the People's Republic of China of 2005 edition and the pharmaceutical characterization showed good stability. In contrast to oral delivery, relatively constant, sustained blood concentration with minimal fluctuation and prolonged peak time were observed over a long period after transdermal administration. The relative bioavailability of felodipine and metoprolol were 275.37% and 189.76% versus oral administration respectively. It was evident that the felodipine-metoprolol-TDDS exhibited good controlled release properties that satisfied the demands of original design that enhancing bioavailability and maintaining appropriate blood levels for a prolonged time without adverse effects associated with frequent oral administration.

Pharmacodynamics and pharmacokinetics of the insulin-mimetic agent vanadyl acetylacetonate in non-diabetic and diabetic rats.

The objectives of this study were to evaluate the pharmacodynamics and pharmacokinetics of vanadyl acetylacetonate (VAC) in rats. Pharmacodynamic study was carried out using non-diabetic and diabetic rats by subcutaneous (s.c.) and intragastric (i.g.) administrations at single dose or multiple doses. Pharmacokinetic study was performed using non-diabetic rats. Results showed that VAC resulted in a significant decrease of plasma glucose levels in diabetic rats in all dosing levels, and nearly restored hyperglycemic values to normal values after s.c. injection at a single dose of 2, 4, and 8 mg vanadium (V)/kg, or after i.g. administration at multiple doses of 3 and 6 mg V/kg once daily for seven consecutive days, respectively. The VAC could be rapidly absorbed and T(max) values ranged from 0.9 +/- 0.3 h for s.c. injection to 3.0 +/- 0.9 h for i.g. administration. The average absolute bioavailabilities for i.g. administrations at a single dose of 3, 6, and 10 mg V/kg were 34.7%, 28.1%, and 22.8%, respectively. After i.g. administration at a single dose of 10 mg V/kg, the average elimination half-lives obtained from non-diabetic rats were very long ranging from 144.7 +/- 8.7 h in plasma to 657.3 +/- 34.8 h in femur tissue. In conclusion, VAC widely distributed in various tissues and accumulated more in the femur tissue. The time to reach maximal vanadium level after s.c. injection or i.g. administration was not coincident with the time to reach maximal hypoglycemic effect. The accumulated vanadium in bone, kidney or other tissues may gradually release and exert a longer action. In present dosing levels and administration routes, VAC was effective for lowering plasma glucose levels in diabetic rats and could reverse the higher triglyceride and cholesterol levels to the normal ranges. VAC did not influence the insulin levels in plasma and not cause obvious toxic signs like diarrhea.