Enhancing Kinase Activity Detection with a Programmable Lanthanide Metal-Organic Framework via ATP-to-ADP Conversion.

Precise modulation of host-guest interactions between programmable Ln-MOFs (lanthanide metal-organic frameworks) and phosphate analytes holds immense promise for enabling novel functionalities in biosensing. However, the intricate relationship between these functionalities and structures remains largely elusive. Understanding this correlation is crucial for advancing the rational design of fluorescent biosensor technology. Presently, there exists a large research gap concerning the utilization of Ln-MOFsto monitor the conversion of ATP to ADP, which poses a limitation for kinase detection. In this work, we delve into the potential of Ln-MOFs to amplify the fluorescence response during the kinase-mediated ATP-to-ADP conversion. Six Eu-MOFs were synthesized and Eu-TPTC ([1,1':4',1″]-terphenyl-3,3'',5,5''-tetracarboxylic acid) was selected as a ratiometric fluorescent probe, which is most suitable for high-precision detection of creatine kinase activity through the differential response from ATP to ADP. The molecular -level mechanism was confirmed by density functional theory. Furthermore, a simple paper chip-based platform was constructed to realize the fast (20 min) and sensitive (limit of detection is 0.34 U/L) creatine kinase activity detection in biological samples. Ln-MOF-phosphate interactions offer promising avenues for kinase activity assays and hold the potential for precise customization of analytical chemistry.

Miositis aguda asociada a infección por virus influenza. Serie de casos en un hospital pediátrico / Acute myositis associated with influenza infection. Case series in a pediatric hospital

La miositis aguda benigna asociada a influenza es una complicación esporádica. En Argentina, en el año 2022, hubo un aumento temprano de la circulación de influenza y del número total de las notificaciones, con la aparición de miositis secundarias. Serie clínica retrospectiva de nueve pacientes pediátricos que consultaron por dolor e impotencia funcional de extremidades inferiores, y enzimas musculares elevadas, en el hospital Pedro de Elizalde de la Ciudad Autónoma de Buenos Aires, entre agosto y octubre del 2022. En todos se detectó infección por virus influenza y se recuperaron sin secuelas. La miositis aguda benigna es una entidad infrecuente en la infancia, cuyo diagnóstico es predominantemente clínico y de recuperación ad integrum. Debe ser sospechada en pacientes con clínica compatible en contexto de alta circulación viral. La vigilancia epidemiológica aporta herramientas para identificar los virus circulantes y sus posibles complicaciones.

Benign acute myositis associated with influenza is a sporadic complication. In Argentina, in 2022, there was an early increase in influenza circulation and the total number of notifications, with the appearance of secondary myositis. Retrospective clinical series of nine pediatric patients who consulted for pain and functional impotence of the lower extremities, and elevated muscle enzymes, at the Pedro de Elizalde hospital in the Autonomous City of Buenos Aires, between August and October 2022. In all of them, infection by influenza virus and recovered without sequelae. Benign acute myositis is a rare entity in childhood, whose diagnosis is predominantly clinical and recovery ad integrum. It should be suspected in patients with compatible symptoms in a context of high viral circulation. Epidemiological surveillance provides tools to identify circulating viruses and their possible complications.

Blood parameters of crioulo breed horse / Parâmetros sanguíneos de potros da raça Crioula

Plasma levels of hematocrit, total plasma protein, fibrinogen, creatine phosphokinase, aspartate transferase, and lactate were analyzed in blood samples of 85 Crioula breed foals, from birth to two years of age. The animals were divided into age groups: G1 (up to 15 days of age; n=70), G2 (from 16 days to one month of age; n=67), G3 (between one and three months of age; n=75), G4 (between three and six months of age; n=64), G5 (between six and nine months of age; n=59), G6 (between nine and 18 months of age; n=39), and G7 (between 18 months and two years of age; n=17). These groups were statistically analyzed by one-way variance analysis (ANOVA) and Tukey's test. Male and female means were compared by Student's t-test. Hematocrit levels were significantly higher up to 90 days of age and in G7 females. Total plasma proteins increased significantly in groups 3, 4, 6, and 7. The highest fibrinogen levels were found in G1. Yet for creatine phosphokinase, the highest concentrations were detected in G5, whereas those of aspartate aminotransferase in G7. The levels of this enzyme remained similar from 30 days to two years of age. Lactate concentrations were higher in G3. We concluded that the sex of the animal had no significant effect on laboratory test interpretations. By contrast, the age of the animal should be considered since relevant variations were observed with time. Nevertheless, specific tables for each analysis should be consulted for interpretation of results.

Com o propósito de estabelecer valores de hematócrito, proteínas plasmáticas totais, fibrinogênio, creatina quinase , aspartato transferase e lactato em potros da raça Crioula, do nascimento até os dois anos, utilizaram-se amostras sanguíneas de 85 animais, divididos pela estratificação etária: Grupo 1 (G1) Até 15 dias de vida (n=70); grupo 2 (G2), entre 16 dias até um mês (n=67); grupo 3 (G3), entre 1 e 3 meses (n=75); grupo 4 (G4), entre 3 e 6 meses (n=64); grupo 5 (G5), entre 6 e 9 meses (n=59); grupo 6 (G6), entre 9 e 18 meses (n=39); e grupo 7 (G7), entre 18 meses até 2 anos (n=17). Foi realizado estudo estatístico entre os grupos pela análise de variância unidirecional (one-wayANOVA), complementada pelo teste de Tukey. Para comparação das médias entre os sexos utilizou-se o teste t de Student. O hematócrito foi significativamente mais elevado até os 90 dias e nas fêmeas do G7. Para proteínas plasmáticas totais, notou-se aumento significativo nos grupos 3, 4, 6 e 7. Os valores de fibrinogênio foram maiores no G1. A CK apresentou maior concentração no G5 e a AST no G7. A AST assumiu valores semelhantes dos 30 dias até os 2 anos. A concentração de lactato foi mais elevada no G3. Conclui-se que na interpretação dos exames laboratoriais de potros da raça crioula, o gênero não interfere significativamente nos resultados, porém a idade deve ser considerada devido à ocorrência de variações relevantes. Recomenda-se que para interpretação sejam consultadas tabelas específicas para cada análise.

Parâmetros sanguíneos de potros da raça Crioula / Blood parameters of crioulo breed horse

Com o propósito de estabelecer valores de hematócrito, proteínas plasmáticas totais, fibrinogênio, creatina quinase , aspartato transferase e lactato em potros da raça Crioula, do nascimento até os dois anos, utilizaram-se amostras sanguíneas de 85 animais, divididos pela estratificação etária: Grupo 1 (G1) Até 15 dias de vida (n=70); grupo 2 (G2), entre 16 dias até um mês (n=67); grupo 3 (G3), entre 1 e 3 meses (n=75); grupo 4 (G4), entre 3 e 6 meses (n=64); grupo 5 (G5), entre 6 e 9 meses (n=59); grupo 6 (G6), entre 9 e 18 meses (n=39); e grupo 7 (G7), entre 18 meses até 2 anos (n=17). Foi realizado estudo estatístico entre os grupos pela análise de variância unidirecional (one-wayANOVA), complementada pelo teste de Tukey. Para comparação das médias entre os sexos utilizou-se o teste t de Student. O hematócrito foi significativamente mais elevado até os 90 dias e nas fêmeas do G7. Para proteínas plasmáticas totais, notou-se aumento significativo nos grupos 3, 4, 6 e 7. Os valores de fibrinogênio foram maiores no G1. A CK apresentou maior concentração no G5 e a AST no G7. A AST assumiu valores semelhantes dos 30 dias até os 2 anos. A concentração de lactato foi mais elevada no G3. Conclui-se que na interpretação dos exames laboratoriais de potros da raça crioula, o gênero não interfere significativamente nos resultados, porém a idade deve ser considerada devido à ocorrência de variações relevantes. Recomenda-se que para interpretação sejam consultadas tabelas específicas para cada análise.

Plasma levels of hematocrit, total plasma protein, fibrinogen, creatine phosphokinase, aspartate transferase, and lactate were analyzed in blood samples of 85 Crioula breed foals, from birth to two years of age. The animals were divided into age groups: G1 (up to 15 days of age; n=70), G2 (from 16 days to one month of age; n=67), G3 (between one and three months of age; n=75), G4 (between three and six months of age; n=64), G5 (between six and nine months of age; n=59), G6 (between nine and 18 months of age; n=39), and G7 (between 18 months and two years of age; n=17). These groups were statistically analyzed by one-way variance analysis (ANOVA) and Tukey’s test. Male and female means were compared by Student’s t-test. Hematocrit levels were significantly higher up to 90 days of age and in G7 females. Total plasma proteins increased significantly in groups 3, 4, 6, and 7. The highest fibrinogen levels were found in G1. Yet for creatine phosphokinase, the highest concentrations were detected in G5, whereas those of aspartate aminotransferase in G7. The levels of this enzyme remained similar from 30 days to two years of age. Lactate concentrations were higher in G3. We concluded that the sex of the animal had no significant effect on laboratory test interpretations. By contrast, the age of the animal should be considered since relevant variations were observed with time. Nevertheless, specific tables for each analysis should be consulted for interpretation of results.

Extremely High Creatine Kinase Activity in Rhabdomyolysis without Acute Kidney Injury.

BACKGROUND Elevation of creatine kinase (CK) activity has been shown to be predictive of acute kidney injury (AKI) in rhabdomyolysis. Patients with extremely high CK activity with preserved renal function are uncommon. This report describes a case of non-traumatic rhabdomyolysis, with a markedly elevated CK activity, without associated AKI. CASE REPORT A 22-year-old male presented with severe generalized myalgias and darkened urine for 1 week prior to his admission. The patient presented to the Emergency Department with initial CK activity of >40 000 U/L and a serum creatinine level of 0.77 mg/dL. Urinalysis was positive for myoglobinuria. Serum cystatin C confirmed an estimated glomerular filtration rate of 144 mL/min/1.73 m². Several causes of rhabdomyolysis, including viral infections, Lyme disease, viral hepatitis, hypothyroidism, and cocaine abuse were investigated; however, all were negative. He was given a bolus of 2 liters of normal saline and continued on intravenous normal saline at 250 mL/hour throughout his hospital stay. Urine output remained adequate. We were able to quantify his serum CK activity by dilution method, which revealed a serum CK activity of >150 000 U/L. His CK levels consistently trended down with treatment. CONCLUSIONS An extremely high CK activity in rhabdomyolysis may lead to AKI. However, preserved kidney function is possible. Young age, no concurrent cocaine use, and adequate oral fluid hydration may prevent AKI in rhabdomyolysis. Physicians need to remain vigilant for cases of rhabdomyolysis that have not yet caused renal compromise.

Biochemical findings in sudden unexpected death in epilepsy: Hospital based case-control study.

PURPOSE: A review study on the biochemistry of epilepsy showed that in epileptic patients, serum glucose and cholesterol concentrations are low, sodium is unaffected, potassium increases, glucose is high and mild hypocalcemia. We have conducted a biochemical study on sudden unexpected death in epilepsy (SUDEP) cases in an attempt to establish the characteristic biochemical values to diagnose these deaths. METHODS: This was a hospital based case-control study done at All India Institute of Medical Sciences, New Delhi for one year. Twenty SUDEP cases and 20 age- and sex-matched controls were included in the study. Femoral blood, cerebrospinal fluid, vitreous humor, and pericardial fluid were biochemically analyzed for sodium, potassium, calcium, glucose, N-acetyl- cysteine activated creatine kinase (CK-NAC) and isoenzyme CK-MB. RESULT: Serum sodium, CK-MB and CK-NAC level was found significantly increased and potassium level was found decreased in SUDEP cases in comparison to non-epileptic deaths. Likewise, in CSF, sodium and CK-NAC was found increased and potassium level was found decreased in SUDEP cases. In vitreous humor, sodium and CK-MB level was found increased and potassium level was found decreased in SUDEP cases in comparison to non-epileptic deaths. In pericardial fluid, sodium, CK-NAC and CK-MB level was found increased and potassium level was found decreased in SUDEP cases in comparison to non-epileptic deaths. CONCLUSION: It concludes that high sodium level and low potassium level could be associated with SUDEP. However, this is a small size study, a larger study is needed to verify the findings. Furthermore, it is difficult to conclude whether these findings are exclusive to SUDEP.

Myocardial protection by propolis during prolonged hypothermic preservation.

Oxidative stress is involved in the pathogenesis of ischemia-reperfusion during myocardial transplantation. Therefore, graft preservation solutions may be improved by supplementation with antioxidants to minimize graft dysfunction caused by cold ischemic injury. Propolis is a polyphenol-rich substance which has an important antioxidant activity. The protective effect of propolis against oxidative stress induced by prolonged cold preservation of heart was investigated. Mice were subjected to a hypothermic model of ischemia in which hearts were preserved for 24 h at 4 °C in Krebs-Hensleit (KH) solution in the absence or presence of propolis concentrations (50, 150 and 250 µg/ml). Levels of released Lactate dehydrogenase (LDH), Creatine phosphokinase (CPK) and Troponine-I (Trop I) were assessed in the preservation solution and histological assessement of heart ischemia injuries was performed. Oxidative stress biomarkers malondialdehyde (MDA) and advanced oxidation protein products (AOPP) and antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were assessed in cardiac tissue. Mitochondria were isolated from stored hearts and production of reactive oxygen species (ROS) was tested. Propolis supplementation protected efficiently hearts during preservation by reducing significantly levels of lipids and proteins oxidation and restoring activities of antioxidant enzymes. Also, propolis preserved tissue integrity altered by hypothermic ischemia in a concentration-dependent manner. Propolis reduced significantly the rate of H2O2 produced by mitochondrial respiration, the best antioxidant effect being obtained at the highest propolis concentration (250 µg/ml). Algerian propolis is a non-temperature sensitive scavenger that protects heart from oxidative damage induced by prolonged hypothermic ischemia.

Examination of the temporal variation of peptide content in decomposition fluid under controlled conditions using pigs as human substitutes.

We report the preliminary observations of the peptide content of decomposition fluid produced under controlled laboratory conditions and in the absence of a soil matrix. Four domestic pig (Sus scrofa domesticus) cadavers were used to model human decomposition over a four-week trial period; physical characteristics were recorded and the peptide components of decomposition fluid was analysed using high performance liquid chromatography-time of flight mass spectrometry. Preliminary data analysis indicated that a range of peptides were consistently detected across the course of the trial period and 27 of these were common to all four cadavers; 22 originating from haemoglobin. The peptides associated with haemoglobin subunit alpha and beta displayed a breakdown pattern that remained consistent for all cadavers for the duration of the trial. Though identification of peptides during decomposition has potential for estimating the time since death, quantification of selected peptides is likely to be essential to identify time-dependent trends.

Successful Long-term Extracorporeal Perfusion of Free Musculocutaneous Flaps in a Porcine Model.

BACKGROUND: Extracorporeal perfusion is a technique that aims to safely prolong tissue preservation by reducing ischemia-reperfusion injury. Free muscle flaps provide a sensitive research model due to their low ischemic tolerance. However, long-term perfusion of free muscle flaps is scarcely researched. The aim of this study was to compare tissue damage in musculocutaneous flaps during 36 h of extracorporeal perfusion versus static cold storage. MATERIALS AND METHODS: Bilateral free rectus abdominis flaps were harvested from five Dutch Landrace pigs (weight: 53-59 kg). Flaps were treated for 36 h according to the following study groups: (1) cold storage at 4°C-6°C (n = 4), (2) perfusion with histidine-tryptophan-ketoglutarate (HTK) at 8°C-10°C (n = 3), (3) perfusion with University of Wisconsin solution (UW) at 8°C-10°C (n = 3). Perfusion fluid samples (creatinine kinase, blood gas) and biopsies for quantitative polymerase chain reaction were collected at multiple time points. Microcirculation was assessed at 24 h of preservation using indocyanine-green fluorescence angiography. Flap weight was measured at the start and end of the preservation period. RESULTS: Successful and stable perfusion for 36 h was achieved in all perfused flaps. The mean creatinine kinase increase in the perfusion fluid was comparable in both the groups (UW: +43,144 U/L, HTK: +44,404 U/L). Mean lactate was higher in the UW group than in the HTK group (6.57 versus 1.07 mmol/L). There were homogenous and complete perfusion patterns on indocyanine-green angiography in both the perfusion groups, in contrast to incomplete and inhomogeneous patterns during cold storage. Expression of genes related to apoptosis and inflammation was lower in perfused flaps than in the cold storage group. Weight increase was highest in the HTK group (78%; standard deviation [SD], 29%) compared with UW (22%; SD, 22%) and cold storage (0.7%; SD, 4%). CONCLUSIONS: Long-term extracorporeal perfusion of free rectus abdominis flaps is feasible. Outcomes in the perfusion groups seemed superior compared to cold storage. Hypotheses gained from this research need to be further explored in a replantation setting.

Noncovalently Associated Peptides Observed during Liquid Chromatography-Mass Spectrometry and Their Effect on Cross-Link Analyses.

Cross-linking mass spectrometry draws structural information from covalently linked peptide pairs. When these links do not match to previous structural models, they may indicate changes in protein conformation. Unfortunately, such links can also be the result of experimental error or artifacts. Here, we describe the observation of noncovalently associated peptides during liquid chromatography-mass spectrometry analysis, which can easily be misidentified as cross-linked. Strikingly, they often mismatch to the protein structure. Noncovalently associated peptides presumably form during ionization and can be distinguished from cross-linked peptides by observing coelution of the corresponding linear peptides in MS1 spectra, as well as the presence of the individual (intact) peptide fragments in MS2 spectra. To suppress noncovalent peptide formations, increasingly disruptive ionization settings can be used, such as in-source fragmentation.

Rabdomiólisis intraoperatoria en cirugía de resección de osteosarcoma de fémur: Reporte de caso y discusión / Case report: Intraoperative rhabdomyolisis after femur osteosarcoma resection

Rhabdomyolysis is a pathology that rarely has causes in the perioperative period, where it has been commonly related as a complication of malignant hyperthermia, prolonged patient positioning with intraoperative muscle compression, in the postoperative period of bariatric surgery and in children. The purpose of this review is to present the case of a 49 year-old male patient, who underwent limb salvage surgery for treatment of a left femur osteosarcoma, with reconstruction via bone transplant and joint prosthesis. During the procedure hyperkalemia and elevation of Creatine-Phosphokinase (CPK) enzyme levels where detected, without changes compatible with renal failure, which required repeated treatment to normalize and that, after ruling out other causes, it was attributed to skeletal muscle destruction during the procedure. Rhabdomyolysis is a phenomenon inherent to this sort of procedures and may manifest initially as laboratory findings and that, if not diagnosed in time, may lead to fatal arrhythmias and acute renal failure.

La rabdomiólisis es una patología que rara vez tiene origen en el período perioperatorio, donde comúnmente se le ha relacionado como complicación de la hipertermia maligna, de decúbitos prolongados con compresión muscular intraoperatoria, del posoperatorio de la cirugía bariátrica y en niños. El objetivo de este trabajo es presentar el caso de un hombre de 49 años, sometido a resección de un osteosarcoma de fémur izquierdo con reconstrucción mediante trasplante óseo y prótesis articular, durante el cual se detectan hiperpotasemia y aumento de la Creatin-Fosfokinasa (CPK), sin alteraciones compatibles con fallo renal, que requirió reiterados tratamientos para la normalización de los valores de kalemia, y que tras descartar otras causas se atribuyó a la destrucción de musculoesquelético durante el procedimiento. La rabdomiólisis es un fenómeno inherente a este tipo de procedimientos y puede manifestarse inicialmente con alteraciones analíticas que, de no ser diagnosticadas en tiempo y forma, pueden llevar a arritmias fatales y fallo renal agudo.

[Gangliocytic paragangliomas: a clinicopathologic study].

Objective: To investigate the clinicopathological features of gangliocytic paraganglioma(GP). Methods: Clinical data and pathological diagnosis of the 4 cases of GP were obtained through the medical record inquiry from January 2011 to December 2017 at the First Affiliated Hospital of Zhengzhou University. Routine HE staining and immunohistochemistry of CKpan, Syn, CgA, CD56, NSE and NF were performed. Clinical follow-up of the patients was obtained through telephone communication. Results: All 4 patients, including 2 male and 2 female patients, presented with intermittent abdominal pain and distention. The median age was 56 years. Preoperative CT showed local thickening of the duodenum wall with slight enhancement in all four cases. Endoscopic ultrasonography showed low level echo in the mucous layer and submucosa involved by the tumor in 3 of 4 cases. The maximal diameter of the tumor ranged from 0.6 to 1.8 cm with an average of 1.2 cm. Microscopically, the tumors consisted of epithelioid, spindle and ganglion-like cells, and the proportion of the three cell types was different among cases. Epithelioid cells expressed CKpan, Syn, CgA and CD56. Spindle cells expressed S-100 protein and SOX-10 and ganglion-like cells expressed NF, Syn, CgA and CD56.All tumour cells expressed NSE. All 4 patients had no recurrence a post-surgery follow-up period of 3 to 30 months. Conclusions: GP of the duodenum is a benign tumor with excellent prognosis after endoscopic excision. Although its incidence is very low, its diagnosis should be considered for any mass lesion of the duodenum, especially involving mucosa and submucosa of the second dudenal segment.

[Clinicopathologic and molecular features of myoepithelial tumors of salivary glands].

Objective: To investigate the clinicopathological, and molecular characteristics of myoepithelial tumors (MTs) of salivary glands. Methods: A total of 37 MTs cases including 13 malignant epithelial tumors (MMTs) and 24 benign epithelial tumors (BMTs) of salivary glands were identified from the archives of the Department of Pathology, General Hospital of Eastern Theater Command, dating from 2006 to 2016. Clinical features, histological patterns, immunohistochemical characteristics and status of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) analysis were reviewed in all cases. Results: Clinically, 37 MTs cases mainly occurred in the parotid glands, when most of the patients presented with painless masses. Of the 13 MMTs cases, male to female ratio was 7∶6, and the median age was 62 years old. Of the 24 BMTs cases, male to female ratio was 5∶7, and the median age was 54 years old. Immunohistochemically, 37 MTs cases were positive for CKpan, and at least one myoepithelial marker. Twenty six of 37 MTs cases were analyzable for the EWSR1 gene break by FISH. Based on the previous evaluation criterion, the EWSR1 translocation was detected in 4 cases of 11 MMTs, and 4 cases of 15 BMTs. According to the main histological composition of tumor cells, 4 EWSR1-positive MMTs covered 2 clear-cell cases and 2 epithelioid-cell cases, when 4 EWSR1-positive BMTs covered 2 clear-cell cases, 1 plasmacytoid-cell case, and 1 spindle-cell case. Conclusions: Males and females are affected equally. MTs express immunoreactivity for CKpan, and at least one myoepithelial marker. The EWSR1 rearrangement is present in a subset of MTs, with variable morphological characteristics, and has no statistical significance on clinical behavior.

Coexistence of anti-HMGCR and anti-MDA5 identified by an unlabeled immunoprecipitation assay in a chinese patient cohort with myositis.

Myositis-specific autoantibodies are important diagnostic and prognostic markers. The aim of our study is to detect anti-3-hydroxy 3-methylutaryl coenzyme A reductase (anti-HMGCR) antibody using novel unlabeled immunoprecipitation (IP) assay and immunoblotting in Chinese patients with myositis and to clarify the features of anti-HMGCR-positive patients. In the present study, we established novel unlabeled IP assay and immunoblotting of HMGCR C-terminus for anti-HMGCR detection. The presence of anti-HMGCR was screened in 181 Chinese patients with myositis. The sera from 12 of 181 patients were positive for anti-HMGCR. The prevalence of anti-HMGCR autoantibody in our cohorts is about 6.6%. Unexpected, coexistence of anti-HMGCR and anti-melanoma differentiation-associated protein (anti-MDA5) were identified in 4 patients with characteristic rash and interstitial lung disease (ILD), but without myasthenia and elevated serum creatine kinase (CK) levels. Other anti-HMGCR positive patients without anti-MDA5 presented with severe proximal muscle weakness. Mean serum CK levels and lactate dehydrogenase (LDH) were significantly higher in anti-HMGCR-positive patients than in antibody-negative patients (P <.05). Muscle biopsies available from 6 anti-HMGCR-positive patients were characterized with prominent myofiber necrosis and regeneration, little or none of inflammatory cell infiltrates. None of anti-HMGCR positive patients in our cohort was exposed to statins. Our data suggested that anti-HMGCR were found to coexist frequently with anti-MDA5 identified by the established unlabeled IP assay and statin exposure is rare in Chinese myositis patients with anti-HMGCR.

A rare cause of proximal muscle weakness: immune necrotising myopathy.

Background Immune-mediated necrotising myopathies are characterised clinically by the subacute onset of proximal limb weakness, accompanied by elevated creatinine kinase levels. They are distinguished from other myopathies by the absence of prominent infiltration of the muscle with inflammatory cells in the biopsies. Case presentation A 44-year-old man presented with upper extremity weakness and dysphagia. Laboratory tests included a creatinine kinase level of 4362 U/L (normal: 52-336 U/L). Rheumatological markers were all negative. A muscle biopsy showed multiple necrotic fibres with minimal inflammatory infiltration. One gram of methylprednisolone (IV) was given, followed by 1 mg/kg of methylprednisolone daily by the oral route. Intravenous immunoglobulin (0.4 mg/kg/day) was given for five days. Muscle weakness regressed and dysphagia disappeared with treatment. The patient remains well in the 23rd month of treatment, taking 5 mg/day prednisolone and monthly intravenous immunoglobulin. Conclusion Treatment of immune-mediated necrotising myopathy can be challenging as evidence-based therapeutic options are limited. It is generally accepted that early and extensive immunosuppression, including glucocorticoids as first-line agents, may be required.

Investigating the possible mechanisms involved in adenosine preconditioning-induced cardioprotection in rats.

BACKGROUND: Adenosine is a breakdown product of adenosine triphosphate and plays an important role in pharmacological preconditioning. The cardioprotective effects of adenosine preconditioning are well established. However, the possible mechanisms need to be explored. AIM: This study was aimed to investigate the possible mechanisms involved in adenosine preconditioning-induced cardioprotection in rats. METHODS: Rat heart was isolated and perfused on Langendorff apparatus. Global ischemia for 30 minutes followed by reperfusion for 120 minutes was employed to produce myocardial injury. Myocardial injury was assessed by measuring myocardial infarct size, release of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and hemodynamic parameters including left ventricular developed pressure (LVDP), dp/dtmax, and dp/dtmin . Serum nitrite levels were measured as an index of nitric oxide release in blood. RESULTS: Adenosine (4 mg/kg) preconditioning significantly decreased ischemia-reperfusion-induced increase in LDH, CK release, infarct size, improved LVDP, dp/dtmax and dp/dtmin, and increased serum nitrite levels. Pretreatment with L-NAME, a specific NOS inhibitor, (5 mg/kg) and montelukast, leukotriene receptor antagonist, (10 mg/kg) significantly abrogated the cardioprotective effect of adenosine preconditioning. However, seratrodast, thromboxane A2 antagonist, (15 mg/kg) had no effect on adenosine-induced cardioprotection. Sodium nitroprusside (SNP) preconditioning also produced cardioprotective effects. However, caffeine (20 mg/kg) (adenosine receptor blocker) and seratrodast (15 mg/kg) had no effect on SNP-induced cardioprotection. Administration of montelukast abrogated the cardioprotective effects of SNP preconditioning-induced cardioprotection. CONCLUSION: Adenosine preconditioning may increase the release of nitric oxide, which in turn may increase the release of cysteinyl leukotrienes to confer cardioprotection.

Thiol/disulfide status regulates the activity of thiol-containing kinases related to energy homeostasis in rat kidney

ABSTRACT Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16th to the 20th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined. Cystine dimethyl ester administration reduced thiol/disulfide ratio and inhibited the kinases activities. Cysteamine administration increased the thiol/disulfide ratio and co-administration with cystine dimethyl ester prevented the inhibition of the enzymes. Regression between the thiol/disulfide ratio, and the kinases activities were significant. These results suggest that redox status may regulate energy metabolism in the rat kidney. If thiol-containing enzymes inhibition and oxidative stress occur in patients with cystinosis, it is possible that lysosomal cystine depletion may not be the only beneficial effect of cysteamine administration, but also its antioxidant and thiol-protector effect.

Acute lumbar paraspinal compartment syndrome: a systematic review.

While still a rare entity, acute lumbar paraspinal compartment syndrome has an increasing incidence. Similar to other compartment syndromes, acute lumbar paraspinal compartment syndrome is defined by raised pressure within a closed fibro-osseous space, limiting tissue perfusion within that space. The resultant tissue ischaemia presents as acute pain, and if left untreated, it may result in permanent tissue damage. A literature search of 'paraspinal compartment syndrome' revealed 21 articles. The details from a case encountered by the authors are also included. A common data set was extracted, focusing on demographics, aetiology, clinical features, management and outcomes. There are 23 reported cases of acute compartment syndrome. These are typically caused by weight-lifting exercises, but may also result from other exercises, direct trauma or non-spinal surgery. Pain, tenderness and paraspinal paraesthesia are key clinical findings. Serum creatine kinase, magnetic resonance imaging and intracompartment pressure measurement confirm the diagnosis. Half of the reported cases have been managed with surgical fasciotomy, and these patients have all had good outcomes relative to those managed with conservative measures with or without hyperbaric oxygen therapy. These good outcomes were despite significant delays to operative intervention. The diagnostic uncertainty and subsequent delay to fasciotomy result from the rarity of this disease entity, and a high level of suspicion is recommended in the appropriate setting. This is particularly true in light of the current popularity of extreme weight lifting in non-professional athletes. Operative intervention is strongly recommended in all cases based on the available evidence.

Thiol/disulfide status regulates the activity of thiol-containing kinases related to energy homeostasis in rat kidney.

Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16th to the 20th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined. Cystine dimethyl ester administration reduced thiol/disulfide ratio and inhibited the kinases activities. Cysteamine administration increased the thiol/disulfide ratio and co-administration with cystine dimethyl ester prevented the inhibition of the enzymes. Regression between the thiol/disulfide ratio, and the kinases activities were significant. These results suggest that redox status may regulate energy metabolism in the rat kidney. If thiol-containing enzymes inhibition and oxidative stress occur in patients with cystinosis, it is possible that lysosomal cystine depletion may not be the only beneficial effect of cysteamine administration, but also its antioxidant and thiol-protector effect.

Ticagrelor Leads to Statin-Induced Rhabdomyolysis: A Case Report.

BACKGROUND Following acute coronary intervention in cardiology patients, the combined medical therapy with the platelet inhibitory drug ticagrelor and a statin medication (e.g., simvastatin) is recommended according to international guidelines. Yet combined therapeutic regimens have the potential of pharmacological interaction with both ticagrelor and simvastatin being metabolized by CYP3A4. Rhabdomyolysis is a known side-effect of statin therapy and combined therapy increases the susceptibility to this complication. CASE REPORT A 72-year-old patient presented to our Emergency Department with typical signs of rhabdomyolysis consisting of muscular cramps and pain in both legs and a significant elevation of creatinine kinase (CK). Five months prior to this presentation, he had been hospitalized due to acute coronary syndrome followed by a coronary intervention of a high-grade left anterior descending artery stenosis. His long-term medication included simvastatin 20 mg daily, which he had taken for several years, and ticagrelor, which had been added to his medication following coronary intervention. The patient showed fast recovery of symptoms and rapid normalization of CK levels upon treatment change from ticagrelor to clopidogrel with a paused statin administration. CONCLUSIONS The combined use of ticagrelor with low dose simvastatin poses a risk for rhabdomyolysis even in patients with normal kidney function. Patients treated with ticagrelor might require changes in statin therapy and dose adjustments in order to avoid pharmacological interactions and higher risk for adverse effects.