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Medicine Oct 2022Muscle cramps are frequently overlooked and worsen the quality of life in patients with chronic liver disease (CLD). Therefore, a valuable biomarker for predicting...
Muscle cramps are frequently overlooked and worsen the quality of life in patients with chronic liver disease (CLD). Therefore, a valuable biomarker for predicting muscle cramps is required in the clinical setting. This study aimed to investigate whether the serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels, a reliable liver fibrosis marker, could predict muscle cramps in patients with CLD. This retrospective study included 80 patients with CLD. Muscle cramps were assessed using a questionnaire regarding their presence, frequency, pain severity, and duration. The associated predictors were analyzed using logistic regression analysis. The diagnostic accuracy and optimal cutoff values were evaluated using receiver operating characteristic curves. Of the 80 patients, 55% had muscle cramps and showed significantly higher serum M2BPGi levels than those without them (4.54 cutoff index [COI] vs 2.20; P = .001). Multivariate analysis revealed that M2BPGi (odds ratio [ORs], 1.19; 95% confidence interval, 1.003-1.42; P = .046) was independently associated with the presence of muscle cramps. The optimal COI value for predicting muscle cramps was 3.95, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 61.4%, 80.6%, 79.4%, 63.0%, and 70.0%, respectively. Patients with a COI value ≥3.95 had a 2-fold higher incidence of muscle cramps than patients with a COI value <3.95 (79% vs 37%; P < .001). M2BPGi levels were also associated with the duration of muscle cramps. Serum M2BPGi appears useful as a biomarker for predicting muscle cramps in patients with CLD.
Topics: Antigens, Neoplasm; Glycosylation; Humans; Liver Cirrhosis; Membrane Glycoproteins; Muscle Cramp; Quality of Life; Retrospective Studies
PubMed: 36254085
DOI: 10.1097/MD.0000000000031145 -
Nutrition (Burbank, Los Angeles County,... May 2022Muscle cramps occur in 33% to 78% of patients with dialysis. The etiology of muscle cramps is poorly understood, and no clear evidence-based prevention or treatment... (Randomized Controlled Trial)
Randomized Controlled Trial
Vitamin K2 as a potential therapeutic candidate for the prevention of muscle cramps in hemodialysis patients: A prospective multicenter, randomized, controlled, crossover pilot trial.
OBJECTIVES
Muscle cramps occur in 33% to 78% of patients with dialysis. The etiology of muscle cramps is poorly understood, and no clear evidence-based prevention or treatment strategies exist. Improved interventions are urgently needed. The aim of this study was to investigate the effect of vitamin K2 in reducing the frequency and severity of muscle cramps in hemodialysis (HD) patients.
METHODS
This multicenter, randomized, placebo-controlled, crossover clinical trial was conducted from June 2019 to May 2020. Each participant received vitamin K2 (360 µg/d) or placebo for two 4-wk phases, and then crossed to the alternative arm for two 4-wk phases after a 2-wk washout. The primary endpoint was the frequency of muscle cramps during HD. The secondary endpoints were severity and duration of muscle cramps during HD.
RESULTS
A total of 523 patients with maintenance HD were screened for muscle cramps, including 41 patients with muscle cramps refractory to conventional interventions, were enrolled. Nineteen patients in the vitamin K2-initial group and 20 in the placebo-initial group completed the protocol, and were included in the final analysis. Vitamin K2 reduced the frequency, duration, and severity of muscle cramps in HD patients (all P < 0.05). The frequency, duration, and severity of muscle cramps in HD patients increased again after crossing over to the placebo. There were no serious adverse events. One patient experienced gastrointestinal discomfort when taking vitamin K2.
CONCLUSIONS
This pilot trial demonstrated that vitamin K2 supplementation could decrease the frequency, duration, and severity of muscle cramps in HD patients.
Topics: Humans; Muscle Cramp; Pilot Projects; Prospective Studies; Renal Dialysis; Vitamin K 2
PubMed: 35203045
DOI: 10.1016/j.nut.2022.111608 -
Roczniki Panstwowego Zakladu Higieny 2023Thailand is a tropical developing country which has a serious increase in health risk due to hot weather exposure among outdoor workers.
BACKGROUND
Thailand is a tropical developing country which has a serious increase in health risk due to hot weather exposure among outdoor workers.
OBJECTIVES
The aims of this study were to compare the factors related to environmental heat exposure in three different seasons, and to assess the relationship between environmental heat and dehydration status in each season among farmworkers in Nakhon Ratchasima, Thailand.
METHODS
A semi-longitudinal study was carried out in 22 male farmworkers throughout a year of farming. The primary data were collected in farmworkers for socio-demographic information, clinical assessments, and heat-related illnesses.
RESULTS
Average of environmental heat index (Median, SD) were severe in summer (WBGT=38.1, 2.8°C), rainy season (WBGT=36.1, 2.1°C), and winter (WBGT=31.5, 2.7°C). Average urine Sp. Gr. in summer, rainy season, and winter were 1.022, 1.020, and 1.018 respectively. The third sentence should be corrected as follows: The Friedman analysis revealed a statistically significant difference between the three different seasons in WBGT (wet bulb globe temperature), body temperature, heart rate (P<0.01), and respiratory rate (P<0.05). There was a statistically significant difference between the three different seasons for skin rash/itching, dizziness, muscle cramp dyspnea (P<0.05), and weakness (P<0.01). Wilcoxon signed-ranks analysis found a significant difference in the medians of the paired sets of urine Sp. Gr. values between baseline and summer (P<0.05). Spearman's rank correlation coefficient did not find a relationship between WBGT and urine Sp. Gr. in the three different seasons.
CONCLUSIONS
This study demonstrated that farmworkers had exposure to environmental heat stress which was expressed through physical changes. Therefore, there is a need for either interventions or guidelines to prevent dehydration for outdoor workers in this region.
Topics: Humans; Male; Hot Temperature; Occupational Exposure; Farmers; Thailand; Longitudinal Studies; Dehydration; Heat Stress Disorders; Health Status
PubMed: 37013902
DOI: 10.32394/rpzh.2023.0250 -
Yonsei Medical Journal Jan 2021Painful muscle cramps are a common complication in liver cirrhosis patients, and no effective treatment is available. This pilot study aimed to evaluate whether taurine... (Clinical Trial)
Clinical Trial
PURPOSE
Painful muscle cramps are a common complication in liver cirrhosis patients, and no effective treatment is available. This pilot study aimed to evaluate whether taurine supplementation improves muscle cramps in Korean cirrhotic patients.
MATERIALS AND METHODS
Ten cirrhotic patients who experienced muscle cramps one or more times/week were enrolled in this prospective single-arm study and administered with an oral taurine solution (1 g/50 mL) thrice a day for 4 weeks. Taurine was discontinued for the subsequent 4 weeks. The frequency and intensity of muscle cramps were evaluated using a questionnaire at weeks 0, 2, 4, 6, and 8 after the start of treatment.
RESULTS
At baseline, the median frequency of muscle cramps was six times/week, and all patients had severe pain. Muscle cramp scores (frequency×intensity) decreased in seven patients by weeks 4 and 8 after treatment initiation. Compared to baseline muscle cramp scores [median 21, interquartile range (IQR): 8-84], median muscle cramp scores were lower at week 4 (6.5, IQR: 3-12, =0.126) and week 8 (5, IQR: 1.5-56, =0.066). All five patients whose baseline plasma taurine levels were below the normal limit showed increased taurine levels at week 4; 60% of them experienced improvements in their muscle cramps. Of the five patients with normal or higher taurine levels, 80% experienced an improvement in symptoms at week 4. The safety and tolerability of the 4-week taurine therapy were excellent.
CONCLUSION
Oral taurine therapy for 4 weeks improved muscle cramps safely in cirrhotic patients.
Topics: Administration, Oral; Adult; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Muscle Cramp; Pilot Projects; Prospective Studies; Taurine; Treatment Outcome
PubMed: 33381931
DOI: 10.3349/ymj.2021.62.1.21 -
Clinical Journal of the American... Oct 2022Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for...
Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in Dialysis: A Kidney Health Initiative Workgroup Report.
Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to () create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, () construct a conceptual model for developing and evaluating a skeletal muscle cramping-specific patient-reported outcome measure, and () identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.
Topics: Humans; Renal Dialysis; Kidney Failure, Chronic; Muscle Cramp; Patient Reported Outcome Measures; Kidney; Muscle, Skeletal
PubMed: 35292531
DOI: 10.2215/CJN.11980921 -
FASEB Journal : Official Publication of... Sep 2022Tree and shrub barks have been used as folk medicine by numerous cultures across the globe for millennia, for a variety of indications, including as vasorelaxants and...
Tree and shrub barks have been used as folk medicine by numerous cultures across the globe for millennia, for a variety of indications, including as vasorelaxants and antispasmodics. Here, using electrophysiology and myography, we discovered that the KCNQ5 voltage-gated potassium channel mediates vascular smooth muscle relaxant effects of barks used in Native American folk medicine. Bark extracts (1%) from Birch, Cramp Bark, Slippery Elm, White Oak, Red Willow, White Willow, and Wild Cherry each strongly activated KCNQ5 expressed in Xenopus oocytes. Testing of a subset including both the most and the least efficacious extracts revealed that Red Willow, White Willow, and White Oak KCNQ-dependently relaxed rat mesenteric arteries; in contrast, Black Haw bark neither activated KCNQ5 nor induced vasorelaxation. Two compounds common to the active barks (gallic acid and tannic acid) had similarly potent and efficacious effects on both KCNQ5 activation and vascular relaxation, and this together with KCNQ5 modulation by other tannins provides a molecular basis for smooth muscle relaxation effects of Native American folk medicine bark extracts.
Topics: Animals; Humans; KCNQ Potassium Channels; Mesenteric Arteries; Rats; Tannins; Vasodilator Agents; American Indian or Alaska Native
PubMed: 35997997
DOI: 10.1096/fj.202200724R -
International Journal of Molecular... Feb 2023Adipose-derived mesenchymal stem cells (ADMSCs) are a type of pluripotent somatic stem cells that differentiate into various cell types such as osteoblast, chondrocyte,...
Adipose-derived mesenchymal stem cells (ADMSCs) are a type of pluripotent somatic stem cells that differentiate into various cell types such as osteoblast, chondrocyte, and neuronal cells. ADMSCs as donor cells are used to produce regenerative medicines at hospitals and clinics. However, it has not been reported that ADMSCs were differentiated to a specific type of neuron with a peptide. Here, we report that ADMSCs differentiate to the cholinergic phenotype of neurons by the SOCS7-derived BC-box motif peptide. At operations for patients with neurological disorders, a small amount of subcutaneous fat was obtained. Two weeks later, adipose-derived mesenchymal stem cells (ADMSCs) were isolated and cultured for a further 1 to 2 weeks. Flow cytometry analysis for characterization of ADMSCs was performed with CD73, CD90, and CD105 as positive markers, and CD14, CD31, and CD56 as negative markers. The results showed that cultured cells were compatible with ADMSCs. Immunocytochemical studies showed naïve ADMSCs immunopositive for p75NTR, RET, nestin, keratin, neurofilament-M, and smooth muscle actin. ADMSCs were suggested to be pluripotent stem cells. A peptide corresponding to the amino-acid sequence of BC-box motif derived from SOCS7 protein was added to the medium at a concentration of 2 μM. Three days later, immunocytochemistry analysis, Western blot analysis, ubiquitination assay, and electrophysiological analysis with patch cramp were performed. Immunostaining revealed the expression of neurofilament H (NFH), choline acetyltransferase (ChAT), and tyrosine hydroxylase (TH). In addition, Western blot analysis showed an increase in the expression of NFH, ChAT, and TH, and the expression of ChAT was more distinct than TH. Immunoprecipitation with JAK2 showed an increase in the expression of ubiquitin. Electrophysiological analysis showed a large holding potential at the recorded cells through path electrodes. The BC-box motif peptide derived from SOCS7 promoted the cholinergic differentiation of ADMSCs. This novel method will contribute to research as well as regenerative medicine for cholinergic neuron diseases.
Topics: Humans; Adipose Tissue; Cell Differentiation; Mesenchymal Stem Cells; Cells, Cultured; Peptides
PubMed: 36769102
DOI: 10.3390/ijms24032786 -
Intractable & Rare Diseases Research Aug 2023Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an intractable neurological disease with autosomal dominant inheritance, four-limb...
Re-survey of 16 Japanese patients with advanced-stage hereditary motor sensory neuropathy with proximal dominant involvement (HMSN-P): Painful muscle cramps for early diagnosis.
Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an intractable neurological disease with autosomal dominant inheritance, four-limb weakness, sensory impairment, and a slowly progressive course. HMSN-P patients develop four-limb paralysis at the advanced-stage, as in amyotrophic lateral sclerosis (ALS). There is a natural 20- to 30-year course from initial painful muscle cramps and four-limb paralysis to respiratory dysfunction. A delay in the diagnosis of HMSN-P occurs due to the 20- to 30-year span from the initial symptom(s) to typical quadriplegia. Its early diagnosis is important, but the involvement of painful muscle cramps as an early symptom has not been clear. Following our earlier survey, we conducted a re-survey focusing on painful muscle cramps, assistive-device use, and hope for specific therapies in 16 Japanese patients with advanced-stage HMSN-P. Fifteen patients presented painful muscle cramps as the initial symptom, and muscle cramps in the lower abdomen including the flank were described by 10 of the patients. The presence of painful muscle cramps including those in the abdominal region may be a clue for the early diagnosis of HMSN-P. Painful abdominal cramps have not described in related diseases, , ALS, spinal muscular atrophy, and Charcot-Marie-Tooth disease. Recent patient-welfare improvements and advances in assistive devices including robot-suit assistive limbs are delaying the terminal state of HMSN-P. Regarding specific therapies for HMSN-P, many patients choose both nucleic acid medicine and the application of induced pluripotent stem cells as a specific therapy for HMSN-P.
PubMed: 37662623
DOI: 10.5582/irdr.2023.01051 -
Journal of the International Society of... Mar 2021Muscle cramp is a painful, involuntary muscle contraction, and that occurs during or following exercise is referred to as exercise-associated muscle cramp (EAMC). The...
BACKGROUND
Muscle cramp is a painful, involuntary muscle contraction, and that occurs during or following exercise is referred to as exercise-associated muscle cramp (EAMC). The causes of EAMC are likely to be multifactorial, but dehydration and electrolytes deficits are considered to be factors. This study tested the hypothesis that post-exercise muscle cramp susceptibility would be increased with spring water ingestion, but reduced with oral rehydration solution (ORS) ingestion during exercise.
METHODS
Ten men performed downhill running (DHR) in the heat (35-36 °C) for 40-60 min to reduce 1.5-2% of their body mass in two conditions (spring water vs ORS) in a cross-over design. The body mass was measured at 20 min and every 10 min thereafter during DHR, and 30 min post-DHR. The participants ingested either spring water or ORS for the body mass loss in each period. The two conditions were counter-balanced among the participants and separated by a week. Calf muscle cramp susceptibility was assessed by a threshold frequency (TF) of an electrical train stimulation to induce cramp before, immediately after, 30 and 65 min post-DHR. Blood samples were taken before, immediately after and 65 min after DHR to measure serum sodium, potassium, magnesium and chroride concentrations, hematocrit (Hct), hemoglobin (Hb), and serum osmolarity. Changes in these varaibles over time were compared between conditions by two-way repeated measures of analysis of variance.
RESULTS
The average (±SD) baseline TF (25.6 ± 0.7 Hz) was the same between conditions. TF decreased 3.8 ± 2.7 to 4.5 ± 1.7 Hz from the baseline value immediately to 65 min post-DHR for the spring water condition, but increased 6.5 ± 4.9 to 13.6 ± 6.0 Hz in the same time period for the ORS condition (P < 0.05). Hct and Hb did not change significantly (P > 0.05) for both conditions, but osmolarity decreased (P < 0.05) only for the spring water condition. Serum sodium and chloride concentrations decreased (< 2%) at immediately post-DHR for the spring water condition only (P < 0.05).
CONCLUSIONS
These results suggest that ORS intake during exercise decreased muscle cramp susceptibility. It was concluded that ingesting ORS appeared to be effective for preventing EAMC.
Topics: Adult; Body Mass Index; Chlorides; Cross-Over Studies; Disease Susceptibility; Drinking; Drinking Water; Exercise; Hematocrit; Hemoglobin A; Hot Temperature; Humans; Magnesium; Male; Mineral Waters; Muscle Cramp; Osmolar Concentration; Potassium; Rehydration Solutions; Running; Sodium; Time Factors; Young Adult
PubMed: 33722257
DOI: 10.1186/s12970-021-00414-8 -
Journal of Neuromuscular Diseases 2024The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1...
BACKGROUND
The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation.
METHODS
Next-generation sequencing including the CLCN1 and SCN4A genes was performed in patients with clinical neuromuscular disorders. Electromyography, Short Exercise Test, in vivo and in vitro electrophysiology, site-directed mutagenesis and heterologous expression were collected.
RESULTS
A heterozygous point mutation (c.1775C > T, p.Thr592Ile) of muscle voltage-gated sodium channel α subunit gene (SCN4A) has been identified in five female patients over three generations, in a family with non-dystrophic myotonia. The muscle stiffness and myotonia involve mainly the face and hands, but also affect walking and running, appearing early after birth and presenting a clear cold sensitivity. Very hot temperatures, menstruation and pregnancy also exacerbate the symptoms; muscle pain and a warm-up phenomenon are variable features. Neither paralytic attacks nor post-exercise weakness has been reported. Muscle hypertrophy with cramp-like pain and increased stiffness developed during pregnancy. The symptoms were controlled with both mexiletine and acetazolamide. The Short Exercise Test after muscle cooling revealed two different patterns, with moderate absolute changes of compound muscle action potential amplitude.
CONCLUSIONS
The p.Thr592Ile mutation in the SCN4A gene identified in this Sardinian family was responsible of clinical phenotype of myotonia.
Topics: Adult; Female; Humans; Middle Aged; Electromyography; Italy; Myotonia; Myotonia Congenita; NAV1.4 Voltage-Gated Sodium Channel; Pedigree; Point Mutation
PubMed: 38427496
DOI: 10.3233/JND-230134