Sinus arrest in familial hypokalemic periodic paralysis caused by SCN4A mutation: a case report.

BACKGROUND: Primary hypokalemic periodic paralysis (HypoPP), a rare skeletal muscle channelopathy resulting in episodic muscle weakness or paralysis under hypokalemic conditions, is caused by autosomal-dominant genetic mutations. HypoPP limits physical activity, and cardiac arrhythmias during paralytic attacks have been reported. We describe a rare familial HypoPP case complicated by sinus arrest and syncope requiring urgent temporary pacemaker implantation. CASE REPORT: A 27-year-old Vietnamese man with a family history of periodic paralysis presented with his third attack of muscle weakness triggered by intense football training the previous day. Clinical and laboratory features justified a HypoPP diagnosis. During intravenous potassium replacement, the patient experienced syncopal sinus arrest requiring urgent temporary pacemaker implantation. The patient gradually improved, responding favorably to oral potassium supplements. Genetic testing revealed an Arg1132Gln mutation in the sodium ion channel (SCN4A, chromosome 17: 63947091). At discharge, the patient received expert consultation regarding nonpharmacological preventive strategies, including avoidance of vigorous exercise and carbohydrate-rich diet. CONCLUSIONS: No evidence has established a relationship between hypokalemia and sinus arrest, and no specific treatment exists for familial HypoPP due to SCN4A mutation. Clinician awareness of this rare condition will promote appropriate diagnostic approaches and management strategies for acute paralytic attacks. Treatment should be tailored according to HypoPP phenotypes and genotypes.

Vitiligo Treatment Impact score (VITs): development and validation of a vitiligo burden of treatment questionnaire using the ComPaRe Vitiligo e-cohort.

BACKGROUND: Vitiligo management is challenging and requires long-term adherence of patients who often complain of the burden associated with treatment. OBJECTIVE: To develop and validate a patient reported measurement of the burden of treatment in vitiligo. METHODS: The study was nested within the ComPaRe Vitiligo e-cohort, an online e-cohort of vitiligo patients in France. Items were derived from a literature review and from the qualitative analysis of a survey using open-ended questions of 204 patients with Vitiligo. Construct validity of the resulting instrument was assessed by comparing the instrument's score to the Dermatology Life Quality Index (DLQI), Vitiligo Impact Patient score (VIPs) and Treatment Burden Questionnaire (TBQ) scores. Reliability was assessed by test-retest with 15 ± 10 days of interval between both assessments. RESULTS: In total, 343 adult participants participated in the validation of the Vitiligo Treatment Impact score (VITs). The VITs is a 19-item questionnaire assessing the burden of treatment in patients with vitiligo with results suggesting four domains ('Finding a doctor', 'Phototherapy', 'Topical treatment' and 'Impact on outdoor activities and photoprotection'). The VITs total score was well correlated with the DLQI, VIP and TBQ scores. Agreement between test and retest was good (ICC 0.705, 95% CI 0.491-0.818). CONCLUSIONS: We developed a patient reported measurement of the burden of treatment in vitiligo with good psychometric properties.

Perspectives on COVID-19 prevention and treatment using herbal medicine in Vietnam: A cross-sectional study.

Introduction: The significance of herbal medicine (HM) during the COVID-19 pandemic has been confirmed. Nevertheless, limited studies have included the people perspectives on COVID-19 prevention/treatment using herbal medicine in Vietnam. Thus, this study tackled the aforementioned issue. Methods: Online-based cross-sectional study was conducted in Vietnamese adults between February-April 2021. Descriptive analysis, regression and Chi-squared tests were implemented for the statistical purposes. Results: total of 787 respondents attended the study, 368 (46.8%) confirmed that they use herbal medicine/nutritional supplements for COVID-19 prevention/treatment. Over 50% of the respondents possessed positive perspective on vitamin C ingestion. Using herbal medicine for external use as a disinfectant was mostly preferred. Respondents who had a 'very good' health self-perception or who lived in rural areas, were more likely to have a positive opinion in the COVID-19 prevention/treatment using herbal medicine. The main barrier for herbal medicine utilization was the deficiency of personal experience or expert advice. Conclusion: The Vietnamese people commonly utilize herbal medicine for the COVID-19 prevention/treatment. These data might help policy-makers in managing the public knowledge and practice on herbal medicine use in Vietnam.

Electroacupuncture prevents cocaine-induced conditioned place preference reinstatement and attenuates ΔFosB and GluR2 expression.

Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse. The transcription factor delta-FosB (ΔFosB) plays a critical role in behavior and pathology after chronic use of cocaine. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models. This experimental study compared the effects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially beneficial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine-induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). EA at LI4 and LI11 significantly prevented cue-induced cocaine CPP reinstatement, whereas needle insertion without electrical stimulation at these acupoints had no such effect. EA also significantly attenuated cocaine-induced increases in ΔFosB and GluR2 expression in the NAc. Unexpectedly, these effects were reversed when GBP was combined with EA. Treatment with EA at LI4 and LI11 prevented cocaine-induced increases in dendritic spine density in the NAc core and shell. Our results suggest that EA at LI4 and LI11 may prevent cocaine relapse by modulating ΔFosB and GluR2 expression, as well as dendritic spine density.

Modified Folfox6 as Adjuvant Chemotherapy in Vietnamese Patients With Colorectal Cancer.

Colorectal cancer is the third most common cancer and the second leading cause of death from cancer worldwide. In Vietnam, the disease is the fifth leading cancer (8.9%), with 14 733 new cases in 2018. In recent years, the mFolfox6 regimen has been indicated commonly as the adjuvant chemotherapy after curative resection for patients with colorectal cancer. However, the efficacy of the regimen in Vietnamese patients has not been assessed and reported. In this retrospective study, we reviewed medical records of 83 patients with stage II or stage III colorectal cancer who received mFOLFOX6 regimen in order to investigate simultaneously survival and safety of this chemotherapy regimen. Three-year overall and disease-free survival were 84.3% and 79.5%, respectively. Our data revealed that postoperative Carcinoma Embryonic Antigen (CEA) level was a significant prognostic factor for survival, with hazard ratio of 3.83 and 3.67, respectively (P < .05), for overall survival and disease-free survival in the elevated CEA level group when compared to the normal CEA level group. The regimen also demonstrated to be well tolerated and can be used in routine practice as an adjuvant chemotherapy.

Specific reversal of multidrug resistance to colchicine in CEM/VLB(100) cells by Gynostemma pentaphyllum extract.

P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR) is perhaps the most thoroughly studied cellular mechanism of cytotoxic drug resistance. Its efflux function can be circumvented by a wide range of pharmacological agents in vitro and in vivo. Most of these agents are pharmaceuticals used clinically for conditions other than cancer. However, their use in alleviating MDR is limited because the concentrations required for inhibition of the pump surpass their dose-limiting toxicity. The aim of this research is to study the role of gypenosides, isolated from Gynostemma pentaphyllum, as modulators of P-gp-mediated MDR in tumor cells, at both cellular and plasma membrane level. In the presence of total gypenoside preparation (0.1 mg/ml), an approximately 15-fold reversal of colchicine (COL) resistance was observed in P-gp-overexpressed CEM/VLB(100) cells. However, the gypenoside sample showed no reversal effect in cells treated with vinblastine and taxol. A purified gypenoside sample (gypenoside fraction 100) exhibited even more significant reversal of COL resistance (approximately 42-fold) in the CEM/VLB(100) cells. Further examination of the reversal effect of fraction 100 in membrane vesicles derived from CEM/VLB(100) cells using the continuous fluorescence method found that gypenoside fraction 100 at 0.1 mg/ml completely abolished the transport of fluorescein-COL.

Transpupillary thermotherapy for occult subfoveal neovessels in age-related macular degeneration: importance of patient pigmentation for the determination of laser settings.

BACKGROUND: Presently the indication for transpupillary thermotherapy (TTT) is the treatment of retrofoveal occult subretinal neovascular membranes (OSRNM) for which PDT (photodynamic therapy) has a limited effect. The diode laser power settings given by the manufacturer (Iridex Co, Mountain View, California) have to be modulated according to several criteria including patient pigmentation. The purpose here was to report on a group of patients that presented chorioretinal atrophy after TTT. METHODS: Thirty-eight eyes of 37 patients with OSRNM due to age-related macular degeneration underwent TTT. Indications to treat were diffuse exudative membranes, limited subfoveal OSRNM with a visual acuity of less than 0.4, or a drop of visual acuity of 3 Snellen lines or more since the previous examination. Dual fluorescein and indocyanine green angiography were used for angiographic follow-up. Treatment was performed according to the manufacturer's parameters. The group of patients that presented chorioretinal atrophy after TTT was analysed in this study RESULTS: Five patients presented a limited or spot-size related post-TTT chorioretinal atrophy. Pre-laser visual acuity was 0.34 +/- 0.13 and post-TTT visual acuity was 0.25 +/- 0.15. The OSRNM had disappeared in all cases. The common denominator in these patients was that they were white haired but upon questioning all happened to be dark-haired in their youth. CONCLUSIONS: Evolution towards atrophy can occur after TTT and probably depends on several factors. We showed that pigmentation is a parameter to be evaluated carefully before TTT and that laser power settings should progressively be diminished with increasing patient pigmentation. In white haired persons the original pigmentary status should be part of the patient history.

The stability of gingerol and shogaol in aqueous solutions.

Gingerols, pungent principles of ginger (the rhizome of Zingiber officinale), are biologically active components that may make a significant contribution towards medicinal applications of ginger and some products derived from ginger. Gingerols, however, are thermally labile due to the presence of a beta-hydroxy keto group in the structure, and undergo dehydration readily to form the corresponding shogaols. This study investigated the stability of [6]-gingerol [5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one] at temperatures ranging from 37 to 100 degrees C in aqueous solutions, at pH 1, 4, and 7. Quantitative measurements of [6]-gingerol and its major degradation product [6]-shogaol [1-(4-hydroxy-3-methoxyphenyl)decan-4-ene-3-one] were performed by HPLC. Kinetics of [6]-gingerol degradation was characterized by least square fitting of a rate equation. It was found that gingerol exhibited novel reversible kinetics, in which it undergoes dehydration-hydration transformations with shogaol, the major degradation product. Degradation rates were found to be pH dependent with greatest stability observed at pH 4. The reversible degradation of [6]-gingerol at 100 degrees C and pH 1 was relatively fast and reached equilibrium within 2 h. Activation energies for the forward and reverse reactions for [6]-gingerol were calculated from the Arrhenius equation using reaction rates obtained at temperatures ranging from 37 to 100 degrees C.

Analysis of a three-dimensional structure of Potato leafroll virus coat protein obtained by homology modeling.

Viruses of the family Luteoviridae are ssRNA plant viruses that have particles that exhibit icosahedral symmetry. To identify the residues that might be exposed on the surface of the Potato leafroll virus (PLRV; genus Polerovirus, family Luteoviridae) capsid, and therefore involved in biological interactions, we performed a structural analysis of the PLRV coat protein (CP) on the basis of comparisons with protein sequences and known crystal structures of CPs of other viruses. The CP of PLRV displays 33% sequence similarity with that of Rice yellow mottle virus (genus Sobemovirus) when the sequences were aligned by using the hidden Markov model method. A structure model for PLRV CP was designed by protein homology modeling, using the crystal structure of RYMV as a template. The resulting model is consistent with immunological and site-directed mutagenesis data previously reported. On the basis of this model it is possible to predict some surface properties of the PLRV CP and also speculate about the structural evolution of small icosahedral viruses.

The control of haemolysis during transurethral resection of the prostate when water is used for irrigation: monitoring absorption by the ethanol method.

OBJECTIVE: To determine whether the addition of ethanol to water for irrigation during transurethral resection of the prostate (TURP) and monitoring breath ethanol could be used to detect irrigant absorption and to limit free plasma haemoglobin in cases of absorption. PATIENTS AND METHODS: One hundred patients (46 in Piteå, Sweden and 54 in Uong bi, Vietnam) underwent surgery for benign prostatic hyperplasia (BPH) under an intermittent irrigation technique using water containing 2% ethanol. An expired breath alcohol meter was used to monitor ethanol in the patients' breath every 5 min. Blood samples taken after TURP were assessed for free haemoglobin in 99 patients, and other markers of haemolysis were also evaluated in the Swedish group. RESULTS: Thirty-two patients had detectable ethanol in their breath. There was a close correlation between the maximum ethanol reading during surgery and the level of free plasma haemoglobin after TURP (r = 0.90, P < 0.001). There was no correlation between the duration of TURP and the free haemoglobin level. CONCLUSION: Monitoring breath ethanol during TURP assesses absorption and so can help to keep control of haemolysis. It is suggested that the value on the alcohol meter should not be allowed to exceed 0.15 (corresponding to a blood ethanol level of 0.15 per thousand), which should maintain the free plasma haemoglobin level at < 1.0 g/L after TURP. Restricting the operative duration per se is not a reliable safety measure.

Effects of blocking GABA degradation on corticotropin-releasing hormone gene expression in selected brain regions.

PURPOSE: The gamma-aminobutyric acid (GABA) degradation blocker gamma-vinyl-GABA (VGB) is used clinically to treat seizures in both adult and immature individuals. The mechanism by which VGB controls developmental seizures is not fully understood. Specifically, whether the anticonvulsant properties of VGB arise only from its elevation of brain GABA levels and the resulting activation of GABA receptors, or also from associated mechanisms, remains unresolved. Corticotropin-releasing hormone (CRH), a neuropeptide present in many brain regions involved in developmental seizures, is a known convulsant in the immature brain and has been implicated in some developmental seizures. In certain brain regions, it has been suggested that CRH synthesis and release may be regulated by GABA. Therefore we tested the hypothesis that VGB decreases CRH gene expression in the immature rat brain, consistent with the notion that VGB may decrease seizures also by reducing the levels of the convulsant molecule, CRH. METHODS: VGB was administered to immature, 9-day-old rats in clinically relevant doses, whereas littermate controls received vehicle. RESULTS: In situ hybridization histochemistry demonstrated a downregulation of CRH mRNA levels in the hypothalamic paraventricular nucleus but not in other limbic regions of VGB-treated pups compared with controls. In addition, VGB-treated pups had increased CRH peptide levels in the anterior hypothalamus, as shown by radioimmunoassay. CONCLUSIONS: These findings are consistent with a reduction of both CRH gene expression and secretion in the hypothalamus, but do not support an indirect anticonvulsant mechanism of VGB via downregulation of CRH levels in limbic structures. However, the data support a region-specific regulation of CRH gene expression by GABA.

Resorcinol derivatives from two Ardisia species.

Besides a series of known sterols and triterpenoids, 2-methyl-5-(Z-nonadec-14-enyl)resorcinol and 5-(Z-nonadec-14-enyl)resorcinol have been isolated from leaves of Ardisia silvestris. The last mentioned diphenol has also been obtained from roots of Ardisia gigantifolia. The structures of these resorcinol derivatives were elucidated.

The double-helical nature of the crystalline part of A-starch.

A new three-dimensional structure of the crystalline part of A-starch is described in which the unit cell contains 12 glucose residues located in two left-handed, parallel-stranded double helices packed in a parallel fashion; four water molecules are located between these helices. Chains are crystallized in a monoclinic lattice with a = 2.124 nm, b = 1.172 nm, c = 1.069 nm and gamma = 123.5 degrees, the c axis being parallel to the helix axis. Systematic absences are consistent with the space group B2. The structure was derived from joint use of electron diffraction of single crystals, X-ray powder patterns decomposed into individual peaks and previously reported X-ray fibre diffraction data after adequate re-indexing. The repeating unit consists of a maltotriose moiety where the glucose residues have the 4C1 pyranose conformation and are alpha(1----4) linked. The conformation of the glycosidic linkage is characterized by torsion angles (phi, psi) which take the values (91.8, -153.2), (85.7, -145.3) and 91.8, -151.3); all the primary hydroxyl groups exist in a gauche-gauche conformation. There are no intramolecular hydrogen bonds. Within the double helix, interstrand stabilization is achieved without any steric conflict and through the occurrence of O(2)...O(6) type hydrogen bonds. The present structure is consistent with both physicochemical and biochemical aspects of the crystalline component of the cereal starch granules.