Salivary Effects of Facial Vibrotactile Stimulation in Patients with Sjogren’s Syndrome and Poor Salivation

We examined the effect of vibrotactile apparatus in patients with Sjögren’s syndrome and others with reduced salivation in comparison to normal subjects. The most effective salivation in normal subjects was produced by 89 Hz vibrotactile stimulation with 9.8 μm amplitude on the parotid or submandibular glands vibrotactile stimuli. First, we examined by measuring the weight of dental cotton rolls positioned at the opening of the secretory duct for total salivation 3 min during resting, and then after 5-min intervals, the weights were measured every 3 min of vibrotactile stimulation on salivary glands. Furthermore, we measured facial temperature around vibrators after 2 min of vibration. We investigated 10 poor salivation patients with Sjögren’s syndrome (8 patients) defined by examinations (contrast study or scintigraphic test) and others (2 patients). About 50% of patients with poor salivation gained recognition for good results, although they had periods of short-term (3 months) and long-term effects (6–7 years) during recuperation. Furthermore, facial skin temperatures on both sides of parotid glands were decreased in Sjogren’s syndrome after vibration, although their temperatures were increased following recovery. Although the mechanism is not clear, we think that vibrotactile stimulation gives activation to salivary glands under the rising facial temperature

Assessment of ATP8B1 Deficiency in Pediatric Patients With Cholestasis Using Peripheral Blood Monocyte-Derived Macrophages

Progressive familial intrahepatic cholestasis type 1 (PFIC1), a rare inherited recessive disease resulting from a genetic deficiency in ATP8B1, progresses to liver failure. Because of the difficulty of discriminating PFIC1 from other subtypes of PFIC based on its clinical and histological features and genome sequencing, an alternative method for diagnosing PFIC1 is desirable. Herein, we analyzed human peripheral blood monocyte-derived macrophages (HMDM) and found predominant expression of ATP8B1 in interleukin-10 (IL-10)-induced M2c, a subset of alternatively activated macrophages. SiRNA-mediated depletion of ATP8B1 in IL-10-treated HMDM markedly suppressed the expression of M2c-related surface markers and increased the side scatter (SSC) of M2c, likely via impairment of the IL-10/STAT3 signal transduction pathway. These phenotypic features were confirmed in IL-10-treated HMDM from four PFIC1 patients with disease-causing mutations in both alleles, but not in those from four patients with other subtypes of PFIC. This method identified three PFIC1 patients in a group of PFIC patients undiagnosed by genome sequencing, an identical diagnostic outcome to that achieved by analysis of liver specimens and in vitro mutagenesis studies. In conclusion, ATP8B1 deficiency caused incomplete polarization of HMDM into M2c. Phenotypic analysis of M2c helps to identify PFIC1 patients with no apparent disease-causing mutations in ATP8B1

Intestinal Atp8b1 dysfunction causes hepatic choline deficiency and steatohepatitis

Abstract Choline is an essential nutrient, and its deficiency causes steatohepatitis. Dietary phosphatidylcholine (PC) is digested into lysoPC (LPC), glycerophosphocholine, and choline in the intestinal lumen and is the primary source of systemic choline. However, the major PC metabolites absorbed in the intestinal tract remain unidentified. ATP8B1 is a P4-ATPase phospholipid flippase expressed in the apical membrane of the epithelium. Here, we use intestinal epithelial cell (IEC)-specific Atp8b1-knockout (Atp8b1IEC-KO) mice. These mice progress to steatohepatitis by 4 weeks. Metabolomic analysis and cell-based assays show that loss of Atp8b1 in IEC causes LPC malabsorption and thereby hepatic choline deficiency. Feeding choline-supplemented diets to lactating mice achieves complete recovery from steatohepatitis in Atp8b1IEC-KO mice. Analysis of samples from pediatric patients with ATP8B1 deficiency suggests its translational potential. This study indicates that Atp8b1 regulates hepatic choline levels through intestinal LPC absorption, encouraging the evaluation of choline supplementation therapy for steatohepatitis caused by ATP8B1 dysfunction

Cystic Kidney Diseases That Require a Differential Diagnosis from Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney disease, with patients often having a positive family history that is characterized by a similar phenotype. However, in atypical cases, particularly those in which family history is unclear, a differential diagnosis between ADPKD and other cystic kidney diseases is important. When diagnosing ADPKD, cystic kidney diseases that can easily be excluded using clinical information include: multiple simple renal cysts, acquired cystic kidney disease (ACKD), multilocular renal cyst/multilocular cystic nephroma/polycystic nephroma, multicystic kidney/multicystic dysplastic kidney (MCDK), and unilateral renal cystic disease (URCD). However, there are other cystic kidney diseases that usually require genetic testing, or another means of supplementing clinical information to enable a differential diagnosis of ADPKD. These include autosomal recessive polycystic kidney disease (ARPKD), autosomal dominant tubulointerstitial kidney disease (ADTKD), nephronophthisis (NPH), oral-facial-digital (OFD) syndrome type 1, and neoplastic cystic kidney disease, such as tuberous sclerosis (TSC) and Von Hippel-Lindau (VHL) syndrome. To help physicians evaluate cystic kidney diseases, this article provides a review of cystic kidney diseases for which a differential diagnosis is required for ADPKD