Serum Electrolyte and Metabolic Changes During Conditioning of Autologous Hematopoietic Stem Cell Transplantation in Patients with Autoimmune Diseases: A Prospective Study in a Single Institution.

BACKGROUND AND OBJECTIVES: A hematopoietic stem cell transplant (HSCT) includes a conditioning regimen which may cause unwanted metabolic changes. We analyzed the changes in electrolytes, glucose, urea, and glomerular filtration rate in patients with multiple sclerosis (MS) who underwent an autologous HSCT employing the "Mexican method." PATIENTS AND METHODS: Serum and urinary electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were prospectively assessed on days -11, -9, and 0 in a group of 75 patients with MS receiving an autologous HSCT employing the "Mexican method," which includes high doses of both cyclophosphamide (Cy, 200 mg/kg) and rituximab (1000 mg). RESULTS: The median age of the patients was 46 years, with a range of 20-65. Baseline data were defined at day -11 of the HSCT. There were significant changes in serum and urinary electrolytes, which diminished substantially after the delivery of high-dose Cy; 12 patients (16%) developed hyponatremia and 2 had hyponatremia-induced seizures, which resulted in hospital admissions. A comparison of baseline blood metabolites with those obtained after the full Cy dosage (day 0) revealed a significant increase in blood glucose and uric acid levels with an associated decrease in serum calcium, sodium, and potassium levels. The salient findings were drug-induced hyponatremia and hyperglycemia. CONCLUSION: Significant changes in serum electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were observed in patients given autologous HSCT for MS employing high-dose Cy. Some of these changes may have clinical consequences, mainly those derived from iatrogenic hyponatremia. No evidence of damage to renal function was observed at day 0.

Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México.

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.

miRNAs in multiple sclerosis: A clinical approach.

Micro-RNAs (miRNAs) are noncoding, single stranded segments of RNA measuring 19 to 25 nucleotides in length. They play an active role in autoimmune diseases, including multiple sclerosis (MS). These structures have been studied given their implication in the process of diagnosis, disease development, treatment and prognosis of MS. Given the progressive and neurodegenerative nature of MS, miRNAs have been identified as critical mediators and molecular pinpoints of the disease, which poses them as excellent candidates for the obtention of suitable biomarkers and treatment targets. This review condenses recent findings on the role of miRNAs in multiple sclerosis, including their role in MS etiology and molecular mechanisms of the disease, exploitation of miRNAs as diagnostic tools and biomarkers, miRNAs as treatment option or target for MS, and their significance as predictors of disease prognosis.

Radical-free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV-induced nonpersistent radicals.

It was recently demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with UV light, enabling radical-free dissolution dynamic nuclear polarization. Although pyruvate is endogenous, the presence of pyruvate may interfere with metabolic processes or the detection of pyruvate as a metabolic product, making it potentially unsuitable as a polarizing agent. Therefore, the aim of the current study was to characterize solutions containing endogenously occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha-ketovalerate (αkV) and alpha-ketobutyrate (αkB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing αkV and αkB were studied with UV-visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with electron spin resonance and compared with pyruvate. The addition of 13 C-labeled substrates to the sample matrix altered the radical yield of the precursors. Using αkB increased the 13 C-labeled glucose liquid-state polarization to 16.3% ± 1.3% compared with 13.3% ± 1.5% obtained with pyruvate, and 8.9% ± 2.1% with αkV. For [1-13 C]butyric acid, polarization levels of 12.1% ± 1.1% for αkV, 12.9% ± 1.7% for αkB, 1.5% ± 0.2% for OX063 and 18.7% ± 0.7% for Finland trityl, were achieved. Hyperpolarized [1-13 C]butyrate metabolism in the heart revealed label incorporation into [1-13 C]acetylcarnitine, [1-13 C]acetoacetate, [1-13 C]butyrylcarnitine, [5-13 C]glutamate and [5-13 C]citrate. This study demonstrates the potential of αkV and αkB as endogenous polarizing agents for in vivo radical-free hyperpolarized MRI. UV-induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality-control tests in clinical applications.

A randomized, 6-wk trial of a low FODMAP diet in patients with inflammatory bowel disease.

OBJECTIVE: The aim of this study was to assess the safety and efficacy of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (LFD) in patients with inflammatory bowel disease (IBD). METHODS: An LFD is associated with symptom improvement in patients with functional intestinal disorders, although its safety and efficacy has not been characterized in patients with IBD. Fifty-five patients with IBD in remission or with mild disease activity were randomized to a 6-wk LFD or standard diet (SD). Disease activity (Harvey-Bradshaw index [HBi], partial Mayo score), fecal calprotectin, and disease-specific quality of life (IBD-Q) were assessed at baseline and at the end of dietary intervention. RESULTS: After the 6-wk dietary intervention, median HBi decreased in the LFD (4; IQR, 3-5 versus 3; IQR, 2-3; P = 0.024) but not in the SD (3; IQR, 3-3 versus 3; IQR, 2-4), whereas Mayo scores were numerically decreased in the LFD group and unmodified in the SD group. Median calprotectin decreased in the LFD (76.6 mg/kg; IQR, 50-286.3 versus 50 mg/kg; IQR, 50.6-81; P = 0.004) but not in the SD group (91 mg/kg; IQR, 50.6-143.6 versus 87 mg/kg; IQR, 50-235.6). Lastly, we observed a barely significant increase in median IBD-Q in the LFD group (166; IQR, 139-182 versus 177; IQR, 155-188; P = 0.05) and no modification in the SD group (181; IQR, 153-197 versus 166; IQR, 153-200). CONCLUSIONS: A short-term, LFD is safe for patients with IBD, and is associated with an amelioration of fecal inflammatory markers and quality of life even in patients with mainly quiescent disease.

Evaluation of clinically applied treatment beams with respect to bunker shielding parameters for a Cyberknife M6.

Compared to a conventional linear accelerator, the Cyberknife (CK) is a unique system with respect to radiation protection shielding and the variety and number of non-coplanar beams are two key components regarding this aspect. In this work, a framework to assess the direction distribution and modulation factor (MF) of clinically applied treatment beams of a CyberKnife M6 is developed. Database filtering options allow studying the influence of different parameters such as collimator types, treatment sites or different bunker sizes. A distribution of monitor units (MU) is generated by projecting treatment beams onto the walls, floor and ceiling of the CyberKnife bunker. This distribution is found to be highly heterogeneous and depending, among other parameters, on the bunker size. For our bunker design, 10%-13% of the MUs are delivered to the right and left wall, each. The floor receives more than 64% of the applied MUs, while the wall behind the patient's head is not hit by primary treatment beams. Between 0% and 5% of the total MUs are delivered to the wall at the patient's feet. This number highly depends on the treatment site, e.g., for extracranial patients no beams hit that wall. Collimator choice was found to have minor influence on the distribution of MUs. On the other hand, the MF depends on the collimator type as well as on the treatment site. The MFs (delivered MU/prescribed dose) for all treatments, all MLC treatments, cranial and extracranial treatments are 8.3, 6.4, 7.7, and 9.9 MU/cGy, respectively. The developed framework allows assessing and monitoring important parameters regarding radiation protection of a CK-M6 using the actually applied treatment beams. Furthermore, it enables evaluating different clinical and constructional situations using the filtering options.

Atividade de óleos e extratos vegetais sobre germinação carpogênica e crescimento micelial de Sclerotinia sclerotiorum / Activity of plant extracts on the carpogenic germination and mycelial growth of Sclerotinia sclerotiorum

A germinação carpogênica e o crescimento micelial de Sclerotinia sclerotiorum foram avaliados sob extratos metanólicos de Annona cacans, A. coriacea, A. crassiflora, A. dioica, A. sylvatica, Geophila repens, Guettarda viburnoides, Palicourea crocea, Schinus terebinthifolius e Trichilia silvatica, e sob as frações hexânica, hidrometanólica, clorofórmica e acetato de etila de A. cacans e óleo essencial de S. terebinthifolius. A concentração utilizada foi de 1.000 ppm para os extratos e de 100 ppm para as frações. Os extratos vegetais e as frações foram incorporados em meio ágar-água, que foi vertido em caixas gerbox com 20 escleródios. O crescimento micelial foi avaliado em óleo essencial de S. terebinthifolius, nas concentrações de 0, 100 e 1.000 ppm, incorporado ao meio BDA (Batata-Dextrose-Ágar). A germinação carpogênica apresentou-se menor sob os extratos de G. repens, P. crocea e S. terebinthifolius e sob as frações acetato de etila e clorofórmica de A. cacans. O número de apotécios formados por gerbox foi menor com o extrato de A. cacans. O crescimento micelial apresentou 10% de inibição na maior concentração do óleo essencial de S. terebinthifolius.(AU)

The efect of methanolic extracts of Annona cacans, A. coriacea, A. crassiflora, A. dioica, A. sylvatica, Geophila repens, Guettarda viburnoides, Palicourea crocea, Schinus terebinthifolius e Trichilia silvatica, and A. cacans hexane, ethyl etila, aqueous and chloroform fractions and the essential oil of S. terebinthifolius on mycelial growth and carpogenic germination of Sclerotinia sclerotiorum was evaluated. Te concentrations are 1,000 ppm for the extracts and 100 ppm for the fractions. To evaluate the germination, carpogenic, extracts and fractions were incorporated in agar-water that was poured into gerboxes where 20 sclerotia were distributed. To evaluate the mycelial growth, essential oil of S. terebinthifolius in concentrations of 0, 100 and 1,000 ppm was incorporated into the PDA and then poured into Petri dishes, to where pathogen mycelial discs were transferred. Extracts of G. repens, P. crocea and S. terebinthifolius and fractions ethyl acetate and chloroform of Annona cacans reduced the carpogenic germination of sclerotia of S. sclerotiorum and the extract of A. cacans reduced the number of apothecia formed. Mycelial growth showed 10% inhibition at the highest concentration of essential oil of S. terebinthifolius.(AU)