Gaucher disease is the most common lysosomal storage disorder. Resveratrol is a natural polyphenol that possesses a wide range of beneficial effects, including anti-inflammatory, anti-oxidant, and neuroprotective activities. The aim of this study was to determine if resveratrol has a therapeutic effect on primary fibroblast cells derived from a patient with type III Gaucher disease. 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of resveratrol on cell survival. The expression levels of apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax), caspase-3, acetyl-coenzyme A acetyltransferase 1 (ACAT1), E3- binding protein (E3BP), and citrate synthase (CS) were evaluated by western blotting to characterize the effect of resveratrol treatment on Gaucher disease cells. Thin-layer chromatography (TLC) was carried out to measure changes in glucosylceramide levels in resveratrol-treated patient cells. Resveratrol increased the viability of patient cells compared to that of untreated control cells. Resveratrol treatment dose-dependently decreased AIF, Bax, and cleaved caspase-3 levels, whereas ACAT1, E3BP, and CS expression dose-dependently increased. TLC analysis showed reduced levels of glucosylceramides in resveratrol-treated patient cells. These findings demonstrate that resveratrol can relieve cellular stress due to glucosylceramide accumulation, and suggest that it should be studied further as a new therapeutic approach for the treatment of Gaucher disease.
Gaucher Disease

Familial hyperkalemic periodic paralysis is an autosomal-dominant channelopathy characterized by reversible paralysis associated with episodic hyperkalemia. Mutations in the skeletal muscle voltage-gated sodium channel gene (SCN4A) have been reported to be responsible for this disorder. Paramyotonia congenita is also caused by mutations in the SCN4A gene. Here, we report the case of a 17-year-old boy who presented with both hyperkalemic periodic paralysis and paramyotonia congenita. A molecular analysis of the SCN4A gene revealed a heterozygous T>C transition at nucleotide 2078, leading to an Ile693Thr mutation. This mutation was absent in the patient’s parents supporting a de novo Ile693Thr mutation in our patient.

Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases.
Ataxia ; Bartter Syndrome ; Brugada Syndrome ; Cardiovascular System ; Channelopathies* ; Diabetes Insipidus, Nephrogenic ; Diabetes Mellitus ; Endocrine System ; Epilepsy, Generalized ; Genetics ; Hypoglycemia ; Hypokalemic Periodic Paralysis ; Immune System ; Ion Channels ; Isaacs Syndrome ; Long QT Syndrome ; Membranes ; Migraine with Aura ; Myasthenia Gravis ; Nervous System ; Neuromyelitis Optica ; Organelles ; Polycystic Kidney Diseases ; Respiratory System ; Seizures, Febrile

STATEMENT OF PROBLEM: Little information is available about the buccal gingival level of multiple implant restorations. PURPOSE: This study was aimed to evaluate the relationship between width and height of buccal soft tissue around single and 2 adjacent implant restorations. MATERIAL AND METHODS: Four implant restoration groups (first and second molars, single second molars, posterior single restorations between teeth, and anterior single restorations between teeth) were randomly chosen from one dental institute. Each group comprised of 6 patients. After 6 months of function, silicone impressions were taken and stone models were fabricated for each restoration group. The stone models were cut in bucco-lingual direction at the most apical point of buccal gingival margin. The height and width of buccal supra-implant soft tissue were measured. One way ANOVA and Tukey HSD post hoc tests were performed to analyze the data obtained (P < .05). RESULTS: The most unfavorable width-height ratio was noted for the group, which was comprised of the second molar in the multiple adjacent (first and second molar) implant-supported restorations. The group also resulted in the shorter height of buccal supra-implant mucosa rather than that of anterior single implant restorations between natural teeth. CONCLUSION: To achieve a favorable level of buccal gingival margin, greater thickness of buccal supra-implant mucosa is required for the implant restorations without a neighboring natural tooth compared to the implant restorations next to a natural tooth.
Humans ; Molar ; Mucous Membrane ; Silicones ; Tooth

We analyzed the mRNA expression patterns of major potassium channel genes to determine the mechanism of hypokalemia in familial hypokalemic periodic paralysis. We used quantitative RT-PCR to examine the mRNA levels of both inward (KCNJ2, KCNJ6, and KCNJ14) and delayed rectifi er (KCNQ1 and KCNA2) potassium channel genes in skeletal muscle cells from both normal and patient groups, prior to and after exposure to 4 mM and 50 mM potassium buffers. Quantitative RT-PCR analysis revealed no changes in the mRNA levels of these genes in normal and patient cells on exposure to 4 mM potassium buffer. However, after exposure to 50 mM potassium buffer, which was used to induce depolarization, normal cells showed a signifi cant decrease in KCNJ2, KCNJ6, and KCNJ14 expression, but no change in KCNQ1 and KCNA2 expression. In contrast, patient cells showed no change in KCNJ2 and KCNJ6 expression, but an increase in KCNJ14 expression. Furthermore, KCNQ1 and KCNA2 showed decreased expression. We found that the expression levels of both inward and delayed rectifi er potassium channel genes in patient cells differ from those in normal cells. Altered potassium channel gene expression in patient cells may suggest a possible mechanism for hypokalemia in familial hypokalemic periodic paralysis.

Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy characterized by episodic muscle weakness with hypokalemia. The respiratory and cardiac muscles typically remain unaffected, but we report an atypical case of a family with hypokalemic periodic paralysis in which the affected members presented with frequent respiratory insufficiency during severe attacks. Molecular analysis revealed a heterozygous c.664 C>T transition in the sodium channel gene SCN4A, leading to an Arg222Trp mutation in the channel protein. The patients described here presented unusual clinical characteristics that included a severe respiratory phenotype, an incomplete penetrance in female carriers, and a different response to medications.
Channelopathies ; Female ; Humans ; Hypokalemia ; Hypokalemic Periodic Paralysis ; Muscle Weakness ; Myocardium ; Penetrance ; Phenotype ; Respiratory Insufficiency ; Sodium ; Sodium Channels

Familial hyperkalemic periodic paralysis (HYPP) is an autosomaldominant channelopathy characterized by transient and recurrent episodes of paralysis with concomitant hyperkalemia. Mutations in the skeletal muscle voltage-gated sodium channel gene SCN4A have been reported to be responsible for this disease. Here, we report the case of a 16-year-old girl with HYPP whose mutational analysis revealed a heterozygous c.2111C>T substitution in the SCN4A gene leading to a Thr704Met mutation in the protein sequence. The parents were clinically unaffected and did not have a mutation in the SCN4A gene. A de novo SCN4A mutation for familial HYPP has not previously been reported. The patient did not respond to acetazolamide, but showed a marked improvement in paralytic symptoms upon treatment with hydrochlorothiazide. The findings in this case indicate that a de novo mutation needs to be considered when an isolated family member is found to have a HYPP phenotype.
Acetazolamide ; Adolescent ; Channelopathies ; Humans ; Hydrochlorothiazide ; Hyperkalemia ; Muscle, Skeletal ; Paralysis ; Paralysis, Hyperkalemic Periodic ; Parents ; Phenotype ; Sodium ; Sodium Channels

Familial hyperkalemic periodic paralysis (HYPP) is an autosomaldominant channelopathy characterized by transient and recurrent episodes of paralysis with concomitant hyperkalemia. Mutations in the skeletal muscle voltage-gated sodium channel gene SCN4A have been reported to be responsible for this disease. Here, we report the case of a 16-year-old girl with HYPP whose mutational analysis revealed a heterozygous c.2111C>T substitution in the SCN4A gene leading to a Thr704Met mutation in the protein sequence. The parents were clinically unaffected and did not have a mutation in the SCN4A gene. A de novo SCN4A mutation for familial HYPP has not previously been reported. The patient did not respond to acetazolamide, but showed a marked improvement in paralytic symptoms upon treatment with hydrochlorothiazide. The findings in this case indicate that a de novo mutation needs to be considered when an isolated family member is found to have a HYPP phenotype.
Acetazolamide ; Adolescent ; Channelopathies ; Humans ; Hydrochlorothiazide ; Hyperkalemia ; Muscle, Skeletal ; Paralysis ; Paralysis, Hyperkalemic Periodic ; Parents ; Phenotype ; Sodium ; Sodium Channels

Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus that presents within the first 6 months of life with remission in infancy or early childhood. TNDM is mainly caused by anomalies in the imprinted region on chromosome 6q24; however, recently, mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1 (SUR1), have also been implicated in TNDM. Herein, we present the case of a male child with TNDM whose mutational analysis revealed a heterozygous c.3547C>T substitution in the ABCC8 gene, leading to an Arg1183Trp mutation in the SUR1 protein. The parents were clinically unaffected and did not show a mutation in the ABCC8 gene. This is the first case of a de novo ABCC8 gene mutation in a Korean patient with TNDM. The patient was initially treated with insulin and successfully switched to sulfonylurea therapy at 14 months of age. Remission of diabetes had occurred at the age of 16 months. Currently, the patient is 21 months old and is euglycemic without any insulin or oral hypoglycemic agents. His growth and physical development are normal, and there are no delays in achieving neurological and developmental milestones.
ATP-Binding Cassette Transporters ; Child ; Diabetes Mellitus ; Humans ; Hypoglycemic Agents ; Infant ; Insulin ; Male ; Parents ; Potassium Channels, Inwardly Rectifying ; Receptors, Drug

Reconstructjon of old anterior cruciate ligament injury was divided into extraarticular and intraarticular group. The intraarticular ligament reconstruction was a reliable method to correct the rotational axis of knee joint instability. Authors studied 10 cases in 10 patients who were treated by reconstruction of anterior cruciate ligament using patellar tendon under arthroscopy from January, 1988 to June, 1989. The follow up period was over 10 months. 7 cases were negative in Lachman test and 2 cases had mild instability of knee joint. The postoperative result was excellent in 3 cases, good in 4 cases, fair in 1 case, and failure in 1 case according to Clancy's evaluation. We concluded that the reconstruction of anterior cruciate ligament injury using patellar tendon under arthroscopy was an effective method in the treatment of old anterior knee instability.
Anterior Cruciate Ligament ; Arthroscopy ; Follow-Up Studies ; Humans ; Knee ; Knee Joint ; Ligaments ; Methods ; Patellar Ligament