Meningococcal Polysaccharide A O-Acetylation Levels Do Not Impact the Immunogenicity of the Quadrivalent Meningococcal Tetanus Toxoid Conjugate Vaccine: Results from a Randomized,Controlled Phase III Study of Healthy Adults Aged 18 to 25 Years

In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ≥1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ≥1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.     

Prevalence of and Predictive Factor for Abdominal Aortic Calcification in Thai Chronic Kidney Disease Patients

Presence and severity of cardiovascular calcifications strongly predict cardiovascular morbidity and mortality in patients with CKD. This multicenter, cross‐sectional study primarily aimed to determine prevalence of abdominal aortic calcification (AAC) detected by plain lateral abdominal radiograph, and secondarily aimed to assess predictive factors for AAC. Patients (N = 1500), aged 18–70 years, with CKD stages 3–5D for ≥3 months prior to evaluation, were enrolled at 24 study centers in Thailand; 54.3% were non‐dialysis patients. The prevalence of AAC was 70.6% and 70.8% in non‐dialysis and dialysis patients, respectively. Patient's advanced age and widening pulse pressure were identified as predictive factors for AAC ≥ 5 in non‐dialysis patients, while patient's age, history of coronary heart disease or diabetes, longer dialysis vintage, and increasing corrected serum calcium or high‐sensitivity C‐reactive protein were identified as such in dialysis patients. With additional regression having covariates in binary, corrected serum calcium ≥9.5 mg/dL gave an OR 1.974 (95% CI: 1.324–2.943) for AAC ≥ 5 among the dialysis patients. AAC in diabetes subgroup (N = 692) was additionally evaluated and found that it was prevalent at 84.7% with increased phosphorus as predictive factor (OR, 1.178; 95% CI: 1.032–1.344) and 1,25 (OH)₂ vitamin D as protective factor (OR, 0.983; 95% CI, 0.970–0.996). The prevalence of AAC in the Thai CKD population is lower than that reported in the literature, and yet the burden is prominent in patients coexisting with diabetes. Variable relationships identified in this study may guide preventive measures against cardiovascular complications in CKD patients.     

Single-dose therapy for giardiasis in school-age children

A randomized controlled trial was carried out to study the efficacy of combined albendazole and praziquantel in the treatment of giardiasis in school-age children. Eighty-four children were randomly allocated to 3 groups: group 1 (n = 31) albendazole 400 mg combined with praziquantel 20 mg/kg; group 2 (n = 26) albendazole 800 mg as a single dose; group 3 (n = 27) tinidazole 50 mg/kg as a single dose. The treatment was considered curative when Giardia was not found in two consecutive stool samples. The parasitological cure rate was 74.2% for combined single-dose albendazole-praziquantel, 50% and 92.6% in the albendazole and tinidazole groups respectively (p = 0.0023). There was no statistically significant difference between the cure rates of the combined regimen and tinidazole (p > 0.05). This combined regimen was considered safe, with only minor side-effects being observed. Of the single-dose regimens, tinidazole still achieves the highest parasitological cure rate for giardiasis. The albendazole-praziquantel combined regimen may be an alternative single-dose therapy for giardiasis in children, especially as this combination will eradicate common intestinal protozoa and co-existing helminths. Whether the dosage of this combination treatment should be adjusted for G. intestinalis remains to be established by further study.     

Abnormal kinetics of erythrocyte sodium lithium countertransport in renal transplant recipients

Cardiovascular disease is now the most common cause of death in renal transplantation. Cyclosporine (CsA)-associated hypertension might be a major cause of cardiovascular risk factors. There is evidence suggesting that one mechanism of CsA toxicity might be mediated through alteration of membrane lipid peroxidation, which can activate cellular pathways. Erythrocyte sodium lithium countertransport (Na/Li CT) is a sensitive membrane protein that is abnormal in several hypertensive-related diseases. We have studied the kinetics of erythrocyte Na/Li CT in 38 renal transplant recipients. Group 1 (15 patients) received CsA, azathioprine, and prednisolone (C+A+P), Group 2 (15 patients) CsA and prednisolone (C+P), and Group 3 (8 patients) azathioprine and prednisolone (A+P). Compared with the normal subjects, the Michaelis constant for extracellular sodium (Km) of erythrocyte Na/Li CT was lower among the CsA-based regimen groups (C+A+P and C+P), but not the A+P group. The maximum velocity (Vmax)/Km ratio was also higher among the C+A+P and C+P groups than the A+P group. These abnormalities of Na/Li CT kinetics might be due to abnormalities of cell membrane functions, caused by immunosuppressive drugs, particularly CsA. Further studies involving the effect of CsA on the physiological function of membrane thiol proteins are required.     

Mucoadhesive curcumin nanospheres: Biological activity, adhesion to stomach mucosa and release of curcumin into the circulation

Although mucoadhesive drug carriers for the gastro-intestinal tract (GIT) have been reported, the mucoadhesive property and drug release characteristics have never been evaluated separately, whilst the adherence of the carriers to the surface of GIT has not been directly visualized. Here, a monopolymeric carrier made from ethylcellulose (EC) and a dipolymeric carrier made from a blend of methylcellulose (MC) and EC (ECMC) were easily fabricated through a self-assembling process and yielded the highest reported curcumin loading of ~ 48-49%. Both curcumin loaded ECMC (C-ECMC) and curcumin loaded EC (C-EC) particles showed an in vitro free radical scavenging activity and a dose-dependent in vitro cytotoxic effect towards MCF-7 human breast adenocarcinoma and HepG2 hepatoblastoma cells in tissue culture. The in vivo evaluation of their adherence to stomach mucosa and their ability to release curcumin into the circulation were carried out through quantification of curcumin levels in the stomach tissue and in blood of mice orally administered with the two spheres. Direct evidence of the adherence of the C-EC and C-ECMC particles along the mucosal epithelia of the stomach is also presented for the first time through SEM images. The mucoadhesive property of self-assembled C-EC nanoparticles is discussed.