Clinical Characteristics, Genetic Features, and Long-Term Outcome of Wilson’s Disease in a Taiwanese Population: An 11-Year Follow-Up Study

Objective@#aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. @*Methods@#aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. @*Results@#aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. @*Conclusion@#aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

Clinicopathological Characteristics of NRG1 Fusion–Positive Solid Tumors in Korean Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown. @*Materials and Methods@#We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed. @*Results@#Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions. @*Conclusion@#Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.

Update on the Epidemiology, Pathogenesis, and Biomarkers of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disorder of the cerebral small blood vessels. It is caused by mutations in the NOTCH3 gene on chromosome 19, and more than 280 distinct pathogenic mutations have been reported to date. CADASIL was once considered a very rare disease with an estimated prevalence of 1.3–4.1 per 100,000 adults. However, recent large-scale genomic studies have revealed a high prevalence of pathogenic NOTCH3 variants among the general population, with the highest risk being among Asians. The disease severity and age at onset vary significantly even among individuals who carry the same NOTCH3 mutations. It is still unclear whether a significant genotype–phenotype correlation is present in CADASIL. The accumulation of granular osmiophilic material in the vasculature is a characteristic feature of CADASIL. However, the exact pathogenesis of CADASIL remains largely unclear despite various laboratory and clinical observations being made. Major hypotheses proposed so far have included aberrant NOTCH3 signaling, toxic aggregation, and abnormal matrisomes. Several characteristic features have been observed in the brain magnetic resonance images of patients with CADASIL, including subcortical lacunar lesions and white matter hyperintensities in the anterior temporal lobe or external capsule, which were useful in differentiating CADASIL from sporadic stroke in patients. The number of lacunes and the degree of brain atrophy were useful in predicting the clinical outcomes of patients with CADASIL. Several promising blood biomarkers have also recently been discovered for CADASIL, which require further research for validation.

Construction and Validation of a Mammalian Expression Vector for in Utero Electroporation Study of miR-3099 in the Mouse Neocortex

@#Introduction: MiR-3099 was reported to play a role in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development. To further explore its potential regulatory effects on embryonic brain development, this study aims to construct and validate an expression vector of miR-3099 for future gain-of-function and loss-of-function studies. Methods: pCAG-eGFP vector was modified to include IRES2 and miR-3099 with 150bp upstream and downstream genomic sequences. The newly constructed vector, pCAG-miR-3099-IRES2-eGFP, consists of CAG promoter. The in vitro expression level of miR-3099 was measured using stem-loop RT-qPCR after it was transfected into 293FT cell. Later, the vector was electroporated into the embryonic brain at E15.5. Three days later, the E18.5 embryonic brain was harvested and cryopreserved. Immunohistochemistry was performed by using antibody against eGFP to validate the in utero expression of the transgene in the neocortex of the brain. Results: Our finding showed that, the expression level of miR-3099 was significantly upregulated (p<0.001) in cells transfected with miR-3099 vector as compared to both negative and empty plasmid control groups. In addition, the expression of eGFP was noted in the brain section indicating that the vectors with or without miR-3099 transgene were successfully transfected into and expressed in the neocortex upon electroporation. Conclusion: The bicistronic expression vector of miR-3099 which was driven by the CAG promoter was successfully constructed, validated and sufficiently delivered to brain cells via the in utero electroporation approach. The regulatory roles of miR-3099 in embryonic brain development can be manipulated using similar approach.

Identification of the PROM1 Mutation p.R373C in a Korean Patient With Autosomal Dominant Stargardt-like Macular Dystrophy

Stargardt-like macular dystrophy 4 (STGD4) is a rare macular dystrophy characterized by bull's eye atrophy of the macula and the underlying retinal pigment epithelium. Patients with STGD4 show decreased central vision, which often progresses to severe vision loss. The PROM1 gene encodes prominin-1, which is a 5-transmembrane glycoprotein also known as CD133 and is involved in photoreceptor disk morphogenesis. PROM1 mutations have been identified as genetic causes for STGD4 and other retinal degenerations such as retinitis pigmentosa. We report a case of STGD4 with a PROM1 p.R373C mutation in a Korean patient. Ophthalmic examinations of a 38-yr old man complaining of decreased visual acuity revealed bilateral atrophic macular lesions consistent with STGD4. Targeted exome sequencing of known inherited retinal degeneration genes revealed a heterozygous missense mutation c.1117C>T (p.R373C) of PROM1, which was confirmed by Sanger sequencing. To the best of our knowledge, this is the first case of a PROM1 mutation causing STGD4 in Koreans.

Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia

Choroideremia is a rare X-linked disorder causing progressive chorioretinal atrophy. Affected patients develop night blindness with progressive peripheral vision loss and eventual blindness. Herein, we report two Korean families with choroideremia. Multimodal imaging studies showed that the probands had progressive loss of visual field with characteristic chorioretinal atrophy, while electroretinography demonstrated nearly extinguished cone and rod responses compatible with choroideremia. Sanger sequencing of all coding exons and flanking intronic regions of the CHM gene revealed a novel small deletion at a splice site (c.184_189+3delTACCAGGTA) in one patient and a deletion of the entire exon 9 in the other. This is the first report on a molecular genetic diagnosis of choroideremia in Korean individuals. Molecular diagnosis of choroideremia should be widely adopted for proper diagnosis and the development of new treatment modalities including gene therapy.

Phytochemical constituents and pharmacological activities of Lagerstroemia floribunda Jack. (Kedah bungor): A Review.

This is the first report on review of Lagerstroemia species which includes the detailed description on phytochemistry and its pharmacological research. Despite being rich in important phytochemicals and having possible medicinal value there is no enough information available on this plant. Lagerstroemia floribunda Jack also known as Thai crape myrtle and kedah bungor, is a species of flowering plant in the Lythraceae family. This delightful ornamental plant is native to subtropical and tropical South-East Asia, from southern China to Myanmar, Thailand, Cambodia, Indo-China and Peninsular Malaysia. The phytoconstituents of Lagerstroemia floribunda includes 23-hydroxyursoIic acid, alphitolic acid, ursolic acid, dihydro-β-cyclopyrethrosin, sesamin, β -sitosterol, clauslactone-K, betulinic acid, lingueresinol, ent-isolariciresinol. Some of the researches that are being carried out on this plant include total phenolic contents and antioxidative activity of its flowers. This review will help to provide detailed information on recent researches done on this plant.

Molecular Phylogenetics of Exophiala Species Isolated from Korea

BACKGROUND: Recently, identification of fungi have been supplemented by molecular tools, such as ribosomal internal transcribed spacer (ITS) sequence analysis. According to these tools, morphological Exophiala species was newly introduced or redefined. OBJECTIVE: This study was designed to investigate the phylogenetics based on ribosomal ITS sequence analysis from clinical Exophiala species isolated in Korea. METHODS: The strains of Exophiala species were 4 clinical isolates of phaeohyphomycosis agents kept in the department of dermatology, Dongguk University Medical Center(DUMC), Gyeongju, Korea. The DNAs of total 5 strains of Exophiala species were extracted by bead-beating method. Polymerase chain reaction of ITS region using the primer pairs ITS1-ITS4, was done and phylogenetic tree contributed from sequences of ITS region from 5 Korean isolates including E. dermatitidis CBS 109154 and comparative related strains deposited in GenBank. RESULTS: The strains of Exophiala species were 3 strains of E. dermatitidis, 1 strain of E. jeanselmei and 1 strain of Exophiala new species. Among the 3 subtypes (type A, B, C) of E. jeanselmei, E. jeanselmei DUMC 9901 belonged to type B. Of the 2 main types of E. dermatitidis (type A, B) and 3 subtypes of E. dermatitidis type A (A0, A1 and A2), two strains (E. dermatitidis CBS 709.95, E. dermatitidis CBS 109154) belonged to A0 subtypes, 1 strain (E. dermatitidis DUMC 9902) A1 subtype, respectively. CONCLUSION: Phylogenetic analysis of ITS region sequence provided useful information not only for new species identification but for the subtyping and origin of Exophiala species.

Effects of acupuncture on post-cesarean section pain / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Post-operation pain is a very subjective phenomenon. The aim of this study was to find out the effects of acupuncture or electro-acupuncture on post-cesarean pain.</p><p><b>METHODS</b>Sixty women, who had had spinal anesthesia during cesarean section at the Department of Obstetrics of China Medical University Hospital, were randomly assigned to the control group, the acupuncture group, and the electro-acupuncture group. After the operation, we applied subjects with acupuncture or electro-acupuncture on the bilateral acupuncture point, San Yin Jiao (Sp6), and the patient controlled analgesia (PCA). The first time of requesting morphine, the frequency of PCA demands in 24 hours, and the doses of PCA used were recorded double blindly. In addition, monitoring the subjects' vital signs, the opioid-related side effects, and the pain scores was done.</p><p><b>RESULTS</b>The results showed that the acupuncture group and the electro-acupuncture group could delay the time of requesting morphine up to 10 - 11 minutes when compared with the control group. The total dose of PCA used within the first 24 hours was 30% - 35% less in the acupuncture group and the electro-acupuncture group when compared with the control group, which was indicated in statistical significance. However, there was no significant difference between the acupuncture group and the electro-acupuncture group. The electro-acupuncture group's and the acupuncture group's pain scores were lower than the control group's within the first 2 hours. Both were statistically significant. However, two hours later, there were no significant differences of the visual analogue scale (VAS) scores between either of the treatment groups and the control group. Finally, the incidence of opioid-related side effects, such as dizziness, was less in the acupuncture group and electro-acupuncture group than in the control group.</p><p><b>CONCLUSIONS</b>This study shows that the application of acupuncture and electro-acupuncture could definitely delay the time of requesting pain relief medication after cesarean section and decrease the PCA doses used within the first 24 hours.</p>

Operative Treatment of the Bilateral 1,4th Brachymetatarsia with Painful Callosity and Hallux Varus using Massive Metatarsal Axial Shortening: A Case Report / 대한족부족관절학회지

In general, the operative treatment of the brachymetatarsia is the lengthening of the affected metatarsal bone due to the cosmetic problem rather than the functional one. We experienced 22 year-old female bilateral congenital foot deformities such as hallux varus and 1,4th brachymetatarsia treated with reverse Scarf osteotomy on the hallux varus and massive axial metatarsal shortening Weil osteotomy on the 2,3,5th metatarsals which could reconstruct the normal metatarsal parabola.

The Mechanism of R-PIA Induced Mechanical Antiallodynia in a Peripheral Neuropathic Rat / 대한마취과학회지

BACKGROUND: The injury by a nerve ligation produces a mechanical allodynia. The antiallodynic effect resulted from intrathecal administration of the adenosine analogues has been well known. ATP-sensitive potassium channel blockers have been known to reverse the effect of some antinociceptive drugs in animal and human studies. Therefore, the present study is to assess the relationship between antiallodynic effect of N6-(R)-phenylisopropyl adenosine (R-PIA) and mitochondrial ATP-sensitive potassium (mKATP) channel in a neuropathic pain model. METHODS: Allodynia was induced in male Sprague Dawley rats by the tight ligation of the left lumbar 5th and 6th spinal nerves. We tested the mechanical allodynia by pricking von Frey filaments to the left hind paw and assessed withdrawal thresholds of paw with up-down method. For the estimation of the antiallodynic effect of R-PIA, R-PIA (0.5, 1 and 2microgram) or saline were administered intrathecally.To investigate the reversal effect on antiallodynic effect of R-PIA, variable amounts of 5-hydroxydecanoate (5-HD, 20, 30 and 40 mg), mKATP channel blocker were administered intraperitoneally at 5 min prior to the intrathecal injection of 2microgram of R-PIA, and the degree of allodynia was assessed. RESULTS: The paw withdrawal threshold was gradually increased with increased dose of R-PIA and reached the maximum level with 2microgram R-PIA (P < 0.05). The increase of paw withdrawal threshold with 2microgram R-PIA was significantly reversed dose-dependently by intraperitoneal pretreatment of 20, 30 and 40 mg/kg 5-HD (P < 0.05). CONCLUSIONS: In our results, intraperitoneal injection of 5-HD before intrathecal injection of R-PIA had reversed the antiallodynic effect of R-PIA. This results suggest that the mechanism of mechanical antiallodynia induced by intrathecal injection of R-PIA may relate with the mK(ATP) channel in a rat model of nerve ligation injury.

Ultrasound Guided Shoulder Joint Injection through Rotator Cuff Interval / 대한통증학회지

BACKGROUND: Shoulder joint injection is currently performed under fluoroscopic or computed tomography scan guidance. We performed this study to determine if an ultrasound guided shoulder joint injection through rotator cuff interval would have clinical usefulness. METHODS: A total of 17 volunteers [12 women, 5 men; mean age 28 yr (23-32 yr)] received shoulder joint injection under multilinear ultrasound (5-10 MHz). Volunteers were positioned supinely on a table with their arm in a neutral position. The anterior shoulder region of the patient was sterilized using povidone iodine. A 24 gauge needle was introduced and directly visualized in real time as it passed obliquely from the skin surface to the inferior space of the biceps tendon. If there was little or no resistance to the injection, a contrast media (omnipaque) was injected and checked fluoroscopically. RESULTS: Ultrasound guided shoulder joint injection through rotator cuff interval was successful in all cases. The average time taken for the procedure was 27.5 +/- 16.5 sec. The vertical distance from skin to the inferior space of the biceps tendon was 1.6 +/- 0.4 cm and the distance of needle from the skin to the inferior space of biceps tendon was 2.8 +/- 0.6 cm. The procedure was well tolerated by all volunteers. CONCLUSIONS: Ultrasound guided shoulder joint injection through rotator cuff interval is an effective, rapid, and easy-to-perform injection technique. Ultrasound guided injection enables exact needle placement and avoids the use of both ionizing radiation and iodinated contrast material.

Anesthesia for a 10-year-old boy with Duchenne muscular dystrophy syndrome: A case report / 대한마취과학회지

Duchenne muscular dystrophy (DMD) is an eventually fatal disorder that is characterized by rapidly progressive muscle weakness and atrophy of muscle tissue. The clinical manifestations of DMD vary depending on the stages of the disease. Succinylcholine-induced hyperkalemia and the administration of volatile anesthetic agents, - particularly halothane, - during acute rhabdomyolysis are more likely to result in cardiac arrest and unsuccessful resuscitation in DMD patients than in the general public. This is a case report of a 10-year-old boy who underwent elective strabismus revision under general anesthesia. Anesthesia was induced and maintained with intravenous propofol and remifentanil, which was started at the targeted effect concentration of 3.0micrometer/ml and 3.5 ng/ml respectively via target controlled infusion (TCI). No inhaled anesthetic was used. In addition, an initial dose 0.4 mg/kg of atracurium was injected intravenously over 15s. The results of this case report found intravenous infusion of propofol, remifentanil and atracurium to be safe because the malignant hyperthermia did not occur.

Clinical and Radiologic Assessment for Anterior Cervical Interbody Fusion with Synthetic Cages

OBJECTIVE: This purpose of this study was to determine the clinical efficiency and applicability, and to analyze the radiologic findings of the anterior cervical approach using two synthetic cages for interbody fusion. METHODS: A total of 41 patients with cervical diseases underwent anterior discectomy and interbody fusion with the PEEK Solis(TM) cage in 21 patients and the carbon composite Osta-Pek(TM) cage in 20 patients. Outcome assessment was done using Odom's criteria. Radiological assessment was performed with respect to subsidence, bony fusion and lordosis. The mean follow-up period was 13 months. RESULTS: There were 34 (92.9%) successful cases. The average height of the disc space 12 months after surgery compared to the height before surgery was increased in 28 cases. The height of the disc space 12 months after surgery compared to the height just after surgery was decreased over 3mm in 4 cases, indicating severe subsidence. The use of these synthetic cages have provided the increase in postoperative cervical lordosis. CONCLUSION: There were no significant differences between the Solis(TM) and Osta-Pek(TM) cages on clinical and radiologic outcomes. Both Solis(TM) and Osta-Pek(TM) cages showed low subsidences and complications associated with hardware with good clinical outcomes, high fusion rates, restored disc heights, and restored cervical lordosis.

Effects of Patients' Position on Blood Pressure and Heart Rate during Spinal Anesthesia for Axillo-femoral Bypass Surgery / 대한마취과학회지

BACKGROUND: Hypotension is one of the most common complications from the spinal anesthesia frequently used for surgery on the lower abdomen or extremities. It might be important in prognostic improvements to maintain cardiovascular homeostasis in elderly or patients with cardiovascular diseases. This study evaluated the effect of the patients' position on the preservation of cardiovascular stability when elderly patients suffering from hypertension undergo surgery for an axillo-femoral arterial bypass. METHODS: 24 patients with hypertension undergoing an elective axillo-femoral bypass surgery were examined. The patients were randomly allocated into two groups (Lateral 20 min group: patients with lateral position for 20 min after spinal anesthesia; Supine group: patients with the supine position immediately after spinal anesthesia). The observers recorded the hemodynamic variables, as well as the loss of sensation on both sides. RESULTS: Considering the changes in the arterial blood pressure and heart rate from the baseline values, patients in the supine group showed a greater decrease in arterial blood pressure and heart rate (P < 0.05). In the lateral 20 min group, there was a lower block level of cold sensation that reflected the sympathetic blockade at the non-operated site (P < 0.05). CONCLUSIONS: The lateral decubitus position for 20 min after spinal anesthesia can contribute to the maintenance of cardiovascular stability during unilateral axillo-femoral bypass surgery in elderly patients with hypertension.

Intrathecal Phenol Saddle Block in Bladder Cancer Patients: Two case reports / 대한마취과학회지

We encountered two bladder cancer patients who suffered from perineal pain that was intractable despite the use of adjuvant medication. A phenol intrathecal (saddle) block was performed without any specific complications. The results were excellent and allowed the systemic opiate dose to be reduced by more than 80%. We report our clinical experience, including a brief review of the relevant literature.

Percutaneous Treatment with Steroid Injections and Distension of Facet Synovial Cyst: A case report / 대한통증학회지

Facet joint synovial cysts are uncommon intraspinal abnormalities, which appear to be secondary to degenerative changes of the joints. They can cause chronic back pain and radiculopathy, as shown in spinal stenosis. When symptomatic cysts fail to respond to conservative measurements, surgical decompression is known as the standard treatment. Percutaneous steroid injections, and distension of the cysts under fluoroscopic guidance, may be a minimally invasive treatment option. Here, the case of a patient with a symptomatic L5-S1 facet joint synovial cyst and left S1 radiculopathy, who responded satisfactorily to percutaneous treatment, is presented.

Isolation of Dermatophytes from Patients with Tinea Pedis Using the Foot-press Method / 대한피부과학회지

BACKGROUND: Although tinea pedis is one of the most prevalent diseases caused by dermatophytes, there have been few studies about distribution of dermatophytes on infected soles for this disease in Korea. OBJECTIVE: The purpose of the study was to investigate the distribution of dermatophytes on infected sole using the new direct culture method (Foot-press method). METHODS: The infected soles of 39 patients were directly pressed onto Sabouraud's dextrose agar with cycloheximide prepared in a large culture dish for a few seconds. The culture media were then incubated at 25degrees C for 1-4 weeks. RESULTS AND CONDLUSION: 1. Dermatophyte colonies were isolated from twenty-eight patients (71.8%). 2. Twenty-four of the isolated dermatophytes were Trichophyton (T.) rubrum (85.7%), and the rest were T. mentagraphytes (14.3%). 3. The number of isolated colonies from each patient range from 1 to 102 (Mean+/-SD, 12.8+/-20.7). Three isolated colonies were most common. 4. The isolation frequencies were higher in the patients of keratotic type and in those with tinea unguium (p<0.05). 5. Positive rate was highest in patients with widely-spread lesion (p<0.05).

The Effect of Low-Dose Atropine on Hypertensive and Hypotensive Stimuli / 대한마취과학회지

BACKGROUND: Vagal cardiac function plays an important role in cardiovascular homeostasis. The purpose of this study was to investigate the association between vagal cardiac function and changes in blood pressure induced by phenylephrine and by thigh cuff deflation after low-dose atropine (LDA)(2microgram/kg) administration. METHODS: Beat-to-beat changes in R-R intervals (RRI) and systolic blood pressures (SBP) were measured in 33 healthy volunteers during spontaneous and controlled (15 min-1) breathing before and after LDA administration. The RMSSD (root mean square of successive differences of RRI), pNN50 (proportion of successive RRI > 50 ms in relation to the total RRI), standard deviation 1 (SD1) from Poincare plots, power spectral densities of heart rate variability (HRV) and SBP variability, and spontaneous baroreflex sensitivity (BRS) by transfer function analysis were assessed. Acute hypertension was induced by phenylephrine (2 microgram/kg), whereas acute hypotension was induced by thigh cuff deflation. RESULTS: RMSSD, pNN50, SD1 of Poincare plots, and the high frequency (HF) power of HRV increased after LDA administration as did spontaneous BRS. Moreover, acute hypertension induced by phenylephrine was significantly attenuated (15.9 +/- 1.9 to 10.8 +/- 3.1 mmHg, P = 0.004) after LDA administration. However, acute hypotension induced by thigh cuff deflation was not significantly changed (13.4 +/- 3.9 to 11.9 +/- 4.2 mmHg, P = 0.62) after LDA administration. Changes in SBP during acute hypertension induced by phenylephrine were significantly correlated with changes in the HF power of HRV (r = -0.60, P < 0.001). CONCLUSIONS: Increasing vagal cardiac function induced by LDA attenuated increased SBP during acute hypertension induced by phenylephrine, but not decreased SBP during acute hypotension induced by thigh cuff deflation in healthy awake subjects.

The Changes in Serum and Cerebrospinal Fluid Ca2+, Mg2+, and Ca2+/Mg2+ Ratio in Neuropathic Rats / 대한마취과학회지

BACKGROUND: Central sensitization of neuropathic pain is associated with an influx of extracellular calcium via the opening of N-methyl-D-aspartate (NMDA) receptor-gated ion channels, which is usually blocked by a magnesium plug. Many studies have found that intrathecal or intraperitoneal magnesium suppress neuropathic pain. Therefore, it is possible that serum and cerebrospinal fluid Ca2+, Mg2+, and Ca2+/Mg2+ ratio are changed in neuropathic pain. The purpose of this study was evaluated changes in serum and cerebrospinal fluid Ca2+, Mg2+, and Ca2+/Mg2+ ratio in neuropathic rats. METHODS: Male Sprague-Dawley rats were prepared with tight ligation of the left lumbar 5th and 6th spinal nerves to produce neuropathic pain. The threshold of mechanical allodynia was evaluated by the up-down method using withdrawal response to a von Frey filaments stimulus on the 3rd, 7th, and 14th day. Rats with a threshold of less than 4 gram were selected as the experimental group. On the 16th day, serum and cerebrospinal fluid Ca2+, Mg2+, and Ca2+/Mg2+ ratio were measured. Experimental group data were then compared with those of an unoperated control group and an unligated sham group; each group contained 10 animals. RESULTS: No statistic differences were found between groups. CONCLUSIONS: Our results suggest that serum and cerebrospinal fluid Ca2+, Mg2+, and Ca2+/Mg2+ ratio in neuropathic rats do not differ from those of normal rats because of physiologic homeostasis is maintained by active transport through the blood-brain-barrier despite of activation of NMDA receptor-gated ion channels. However, we believe that the Mg2+ ion-dependent voltage-gating in rats with neuropathic pain may be deficient in a chronic condition due to a decreased Mg2+ binding affinity of the NMDA receptor-gated channel, as has been found in hippocampal granule cells in epileptic rats.