Hibiscus sabdariffa increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B12 deficiency with neurological symptoms

The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB₁₂) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B₁₂‐deficient patients (vit B₁₂ < 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. To understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B₁₂ level increased from 55.1 ± 36.9 to 1330 ± 335.5 pg/mL at day 10 and 431.0 ± 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose‐dependent manner with HB₁₂. The apparent permeability of Hdrx was P_app = 34.9 ± 4.6 × 10^?6 cm/s in the presence of 3 mg/mL (HB₁₂B) compared to the control P_app = 6.2 ± 0.7 × 10^?6 cm/s. (ii) Total transepithelial electrical conductance (G_t) increased in dose‐dependent manner with HB₁₂, G_t = 161.5 ± 10.8 mS/cm² with HB₁₂B (Hdrx 1 mg + HS 3 mg) compared to the control Hdrx, G_t = 28.7 ± 4.0 mS/cm². In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS.     

A novel <Emphasis Type="Italic">PCLN-1</Emphasis> gene mutation in familial hypomagnesemia with hypercalciuria and atypical phenotype

Familial hypomagnesemic hypercalciuria and nephrocalcinosis (FHHNC [MIM 248250]) is a rare renal tubular disorder characterized by impaired reabsorption of magnesium and calcium in the thick ascending limb of Henle’s loop (tALH), causing renal magnesium wasting and hypercalciuria. Patients with FHHNC usually present with recurrent urinary tract infections, polyuria, nephrolithiasis (NL) and nephrocalcinosis (NC) with many progressing to chronic renal failure (CRF). We have shown recently that loss of function mutations in paracellin-1 PCLN-1/claudin-16, a renal tight junction protein located in the TAL, are causative of FHHNC. We present clinical and molecular studies on a highly inbred family with FHHNC in association with an unusual phenotype in that all affected members were extremely short. Affected individuals were found to be homozygous for marker D3S1314 on chromosome 3q. Sequencing of the PCLN-1/claudin-16 gene revealed a previously unknown point mutation at S235Y on exon 4 on the 4th transmembrane domain, providing additional evidence that inactivating mutations in the PCLN-1/claudin-16 gene result in FHHNC.