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Abstract Background Acute lymphoblastic leukemia is the most common type of cancer in children. Most often it affects the age group between 2 and 5 years of age. Studies have shown an improvement in general survivability, more than 90% 5-year overall survival (OS). Current treatment protocols for acute lymphoblastic leukemia require verification of the presence of favorable and unfavorable genetic abnormalities, which help qualify patients to the appropriate risk group and select a more suitable treatment. The presence of the BCR/ABL1 fusion gene stratifies the patient into a high-risk group and requires special treatment with tyrosine kinase inhibitors (TKI). The three dominant mRNA transcripts are e1a2, e13a2, and e14a2. Nevertheless, cases of atypical BCR/ABL1 transcripts have also been reported. Case presentation This paper presents the case of a pediatric patient with Ph + B-cell precursor acute lymphoblastic leukemia with rare atypical e8a2 BCR/ABL1 fusion transcript. Our patient achieved complete remission after 33 days of treatment. Molecular and cytogenetic studies in TP1 did not reveal the presence of the BCR/ABL1 transcript. The PCR-MRD test in TP1b was negative, the patient did not require hematopoietic stem cell transplantation. Conclusion Genetic evaluation of the bone marrow sample is crucial in the initial stage of the diagnosis. Fluorescent in situ hybridization and reverse transcriptase polymerase chain reaction with Sanger sequencing are the appropriate methods used in the detection of rare variants of BCR/ABL1 transcripts.

Background:. Lower capsular contracture rates have been observed with peri-prosthetic fat grafting. We investigated the effect of fat grafting on capsular characteristics and peri-prosthetic collagen density, content, and fiber alignment. Methods:. Forty miniature tissue expanders were placed on the backs of 20 rats. After four weeks, both inguinal fat pads were harvested, homogenized, and injected into peri-prosthetic tissue of the right tissue expander (fat graft) while the left served as control. The animals were killed at three (10 rats) and 12 weeks (10 rats), and full thickness peri-prosthetic samples were histologically processed for morphology (H&E) and collagen type and content (picrosirius red). Results:. An 8.1% increase in adipose peri-prosthetic thickness was associated with a 10% decrease in collagen content at any time point (P = 0.004). Fat-grafted capsules displayed a 59% reduction in % total collagen when compared with controls (P < 0.001). There were no differences in capsular thickness. Fat-grafted samples were 54 times more likely to have a higher inflammation score and 69 times more likely to have a lower capsular density score than their nongrafted counterparts (P < 0.001 and P = 0.001, respectively). The extent of inflammation decreased over time in all samples (P = 0.002). Additionally, fat-grafted samples were 67 times more likely to have a lower fiber alignment score than the controls (P < 0.001). Conclusions:. Enhancement of peri-prosthetic tissue with fat grafting decreases collagen content, density, and fiber alignment of implant capsules. These findings support clinical application of fat grafting in prosthetic breast surgery to potentially decrease capsular contracture.

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that TLR4 rs4986791, TLR9 rs5743836, and NOD2 rs2066847 were associated with CRP levels, while RLR-1 rs10738889 was associated with LDH level. Furthermore, we found TLR3 rs5743305 AA to be more common in patients with infections. We also found TLR9 rs187084 C to be associated with more favorable risk, and RLR-1 rs9695310 GG with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML.

Background Serum indoxyl sulfate (IS) levels depend on the production of indole in the gut. The biological effects of IS in the vascular bed could be confirmed by changes in the levels of individual serum proteins during normal pregnancy and in the postpartum period as compared with non-pregnant controls. Albumin (Alb) and α1-acid glycoprotein (AGP, orosomucoid) are the most abundant serum carrier proteins with potential interrelationships with serum levels of IS. Methods Serum levels of IS, Alb and AGP were measured in 84 pregnant women in the first, second and third trimester of pregnancy and in the postpartum period, as well as in non-pregnant controls (n = 20), using ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry (IS), colorimetric assay (Alb) and immunoturbidimetric assay (AGP). Results The postpartum serum levels [mg/L] of IS were lower (p = 0.027) than in the second trimester (mean±SD: 0.85±0.39 vs 0.58±0.32). There were no differences in the IS to ALB ratio calculated in the three trimesters of pregnancy, the postpartum period, and in the non-pregnant controls. The IS/AGP ratio increased from the first to the second trimester (p = 0.039), and decreased in the postpartum period (pConclusions The variability of the serum IS/AGP ratio during pregnancy and in the postpartum period may reflect shared involvement in the regulation of their intravascular relationships. The link between serum levels of IS derived from the gut and AGP could serve a potential biomarkers of maternal intestinal metabolism during pregnancy and postpartum.

Sorafenib (SR) is one of the most potent UGT (1A1, 1A9) inhibitors (in in vitro tests). The inhibition of UGT1A1 may cause hyperbilirubinaemia, whereas the inhibition of UGT1A9 and 1A1 may result in drug-drug interactions (DDIs). Tapentadol (TAP) is a synthetic μ-opioid agonist and is used to treat moderate to severe acute pain. Tapentadol is highly glucuronidated by the UGT1A9 and UGT2B7 isoenzymes. The aim of the study was to assess the DDI between SR and TAP.Wistar rats were divided into three groups, with eight animals in each. The rats were orally treated with SR (100 mg/kg) or TAP (4.64 mg/kg) or in combination with 100 mg/kg SOR and 4.64 TAP mg/kg. The concentrations of SR and sorafenib N-oxide, TAP and tapentadol glucuronide were respectively measured by means of high-performance liquid chromatography (HPLC) with ultraviolet detection and by means of ultra-performance liquid chromatography-tandem mass spectrometry.The co-administration of TAP with SR caused TAP maximum plasma concentration (Cmax) to increase 5.3-fold whereas its area under the plasma concentration-time curve (AUC0-∞) increased 1.5-fold. The tapentadol glucuronide Cmax increased 5.3-fold and whereas its AUC0-∞ increased 2.0-fold. The tapentadol glucuronide/TAP AUC0–∞ ratio increased 1.4-fold (p = 0.0118). TAP also increased SR Cmax 1.9-fold, whereas its AUC0-∞ increased 1.3-fold. The sorafenib N-oxide Cmax increased 1.9-fold whereas its AUC0-∞ increased 1.3-fold. The sorafenib N-oxide/SR AUC0–t ratio increased 1.4-fold (p = 0.0127).The results show that the co-administration of sorafenib and tapentadol increases the exposure to both drugs and changes their metabolism. In consequence, the pharmacological effect may be intensified, but the toxicity may increases, too.

A combination of the tyrosine kinase inhibitor—sorafenib—and the opioid analgesic—morphine—can be found in the treatment of cancer patients. Since both are substrates of P-glycoprotein (P-gp), and sorafenib is also an inhibitor of P-gp, their co-administration may affect their pharmacokinetics, and thus the safety and efficacy of cancer therapy. Therefore, the aim of this study was to evaluate the potential pharmacokinetic drug–drug interactions between sorafenib and morphine using an animal model. The rats were divided into three groups that Received: sorafenib and morphine (ISOR+MF), sorafenib (IISOR), and morphine (IIIMF). Morphine caused a significant increase in maximum plasma concentrations (Cmax) and the area under the plasma concentration–time curves (AUC0–t, and AUC0–∞) of sorafenib by 108.3 (p = 0.003), 55.9 (p = 0.0115), and 62.7% (p = 0.0115), respectively. Also, the Cmax and AUC0–t of its active metabolite—sorafenib N-oxide—was significantly increased in the presence of morphine (p = 0.0022 and p = 0.0268, respectively). Sorafenib, in turn, caused a significant increase in the Cmax of morphine (by 0.5-fold, p = 0.0018). Moreover, in the presence of sorafenib the Cmax, AUC0–t, and AUC0–∞ of the morphine metabolite M3G increased by 112.62 (p < 0.0001), 46.82 (p = 0.0124), and 46.78% (p = 0.0121), respectively. Observed changes in sorafenib and morphine may be of clinical significance. The increased exposure to both drugs may improve the response to therapy in cancer patients, but on the other hand, increase the risk of adverse effects.

Eagle syndrome consists of symptoms resulting from the elongation and excessive calcification of the styloid process of the temporal bone and calcification of the ligaments associated with this process. The main symptoms of this syndrome are the feeling of a foreign body in the throat, dysphagia and pain localized in the temporomandibular region, neck and ear. The authors describe the case report of a previously healthy 39-year-old Caucasian male that complained of discomfort and foreign body sensation in his throat. Computed tomography (CT) showed the presence of an elongated styloid process bilaterally with clear predomination at the left side. The patient underwent laryngological and surgical consultation. Due to the lack of symptoms related to the compression of the carotid arteries, no surgery was recommended. In summary, Eagle’s syndrome is a rare condition characterized by craniofacial pain or foreign body sensation that should be considered, especially if the pain is unilateral. CT imaging in his case was a perfect tool and enabled a suitable diagnosis of this rare syndrome.

Isolated tricuspid ring annuloplasty remains the surgical standard for functional tricuspid regurgitation repair but offers suboptimal results when right ventricular dilation and remodeling along with papillary muscle displacement is present. Addressing subvalvular remodeling with papillary muscle approximation may improve clinical outcomes. Functional tricuspid regurgitation and biventricular dysfunction were induced in 8 healthy sheep by rapid ventricular pacing (200-240 bpm) for 27 ± 6 days. Subsequently, animals underwent cardiopulmonary bypass for implantation of sonomicrometry crystals on the tricuspid annulus, right ventricle, and papillary muscle tips. Papillary approximation sutures were anchored between anterior-posterior and anterior-septal papillary muscles and externalized through right ventricular free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, sequential papillary muscle approximations were performed. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were collected at baseline and after each papillary muscle approximation. With rapid pacing, right ventricular fractional area change decreased from 59 ± 6% to 38 ± 8% (P <.001), whereas tricuspid annulus diameter increased from 2.4 ± 0.3 cm to 3.3 ± 0.6 cm (P =.003). Tricuspid regurgitation (0-4+) increased from +0 ± 0 to +3.3 ± 0.7 (P <.001). Both anterior–posterior and anterior–septal papillary muscle approximation significantly reduced functional tricuspid regurgitation from +3.3 ± 0.7 to +2 ± 0.5 and +1.9 ± 0.6, respectively (P <.001). Reduction of tricuspid insufficiency with both subvalvular interventions was associated with decreased distance of the anterior papillary muscle to the annular centroid. Papillary muscle approximations were effective in reducing severe ovine functional tricuspid regurgitation associated with right ventricular dilation and papillary muscle displacement. Further studies are needed to evaluate efficacy of this adjunct to ring annuloplasty in repair of severe functional tricuspid regurgitation. [Display omitted] [ABSTRACT FROM AUTHOR]

Decompression sickness is a group of pathological processes occurring in the body, following its exposure to an excessive drop in atmospheric pressure. The paper presents a case of a 62-year-old patient with no substantial disease history, a long-standing professional military pilot who was diagnosed with multifocal, bone manifestation of decompression sickness during the diagnosis of right knee joint injury following a torsion injury. The case was presented to draw attention to the usefulness of occupational history in the process of diagnosing osteoarticular system diseases. Med Pr 2013;64(2):273–279

The aim of the present study was to isolate mesenchymal stromal cells (MSC) with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI). The study aimed also to investigate the feasibility of xenogeneic MSCs implantation.MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO). Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb). MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed.In two murine models (hindlimb ischemia and MI) we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart.

Previously we had shown that ammonia stimulates nitric oxide (NO) synthesis in astrocytes by increasing the uptake of the precursor amino acid, arginine via the heteromeric arginine/glutamine transporter y+LAT2. Ammonia also increases the concentration in the brain of the endogenous inhibitor of nitric oxide synthases (NOS), asymmetric dimethylarginine (ADMA), but distribution of ADMA surplus between the intraastrocytic and extracellular compartments of the brain has not been studied. Here we tested the hypothesis that ammonia modulates the distribution of ADMA and its analog symmetric dimethylarginine (SDMA) between the two compartments of the brain by competition with arginine for the y+LAT2 transporter. In extension of the hypothesis we analyzed the ADMA/Arg interaction in endothelial cells forming the blood-brain barrier. We measured by high-performance liquid chromatography (HPLC) and mass spectrometry (MS) technique the concentration of arginine, ADMA and SDMA in cultured cortical astrocytes and in a rat brain endothelial cell line (RBE-4) treated with ammonia and the effect of silencing the expression of a gene coding y+LAT2. We also tested the expression of ADMA metabolism enzymes: protein arginine methyltransferase (PRMT) and dimethylarginine dimethyl aminohydrolase (DDAH) and arginine uptake to astrocytes. Treatment for 48 h with 5 mM ammonia led to an almost 50% reduction of ADMA and SDMA concentration in both cell types, and the effect in astrocytes was substantially attenuated by silencing of the Slc7a6 gene. Moreover, the y+LAT2-dependent component of ammonia-evoked arginine uptake in astrocytes was reduced in the presence of ADMA in the medium. Our results suggest that increased ADMA efflux mediated by upregulated y+LAT2 may be a mechanism by which ammonia interferes with intra-astrocytic (and possibly intra-endothelial cell) ADMA content and subsequently, NO synthesis in both cell types.

Syndecan-1 (CD138) is a transmembrane heparin sulfate proteoglycan expressed on distinct stages of differentiation of B-lymphoid cells. Its prognostic value in B-cell chronic lymphocytic leukemia (B-CLL) has not been evaluated so far. The serum concentration of sCD138 and some angiogenesis-involved cytokines: vascular endothelial growth factor (VEGF), basis fibroblast growth factor (bFGF), and endostatin were studied in 52 previously untreated patients with B-CLL. We found that bFGF and sCD138 levels were significantly higher in B-CLL patients than in controls. In patients with sCD138 level or endostatin level below the median value the lymphocyte count was higher than in patients with serum level of those cytokines above the median value. In patients with progressive disease bFGF level was significantly higher and sCD138 level significantly lower than in patients with stable one. Moreover, high sCD138 level was associated with longer lymphocyte doubling-free survival, and, on the limit of statistical significance, a high endostatin level was associated with shorter progression-free survival. We conclude that serum sCD138 level is increased in early stage B-CLL patients and may have a positive prognostic value as to the dynamics of the disease.

The cardiovascular health (CVH) score constitutes a reliable and measurable indicator of CVH proposed by the American Heart Association (AHA) calculated based on seven fundamental parameters, that is, smoking, body mass index, physical activity, healthy diet score, blood pressure, blood cholesterol, and fasting plasma glucose. The size and activity of carotid body (CB) play an important role in the pathogenesis of the cardiovascular system. The objective of this study was to define the relationship between the AHA CVH score and the volume of CB (V rCB+lCB ) estimated based on computed tomography angiography (CTA) in patients with arterial hypertension. Studies were conducted on a group of 57 patients with arterial hypertension (age: 70.74 ± 8.21 years). The CVH score was calculated, and CTA of carotid arteries was carried out for all patients. The CB analysis was performed based on delayed phase imaging obtained from CTA of carotid arteries. Based on the CVH score value, CVH was determined as optimal (CVH score between 10 and 14 points), average (5 and 9 points), or inadequate (0 and 4 points). CVH score in the studied group of patients was 6.53 ± 1.81, whereas V rCB+lCB value was 38.58 ± 18.43 mm 3 . Patients with an inadequate CVH score (0–4 points) have statistically significantly higher V rCB+lCB , and they are fraught with V rCB+lCB ≥ median much more often than patients with an optimal CVH score (10–14 points). The receiver operating characteristic curve indicated a CVH score value of 6 as an optimal cutoff point to predict V rCB+lCB ≥ median. The CVH score ≤6 criterion indicates V rCB+lCB ≥ median with sensitivity of 58.6% and specificity of 71.4%. In the regression analysis, it was indicated that lower partial scores for physical activity, healthy diet score, and blood pressure in the AHA CVH evaluation constitute independent risk factors for higher V rCB+lCB . In the studied group of patients with arterial hypertension, an inversely proportional dependence between the CVH score and the size of CB is observed in CTA of carotid arteries. [ABSTRACT FROM AUTHOR]

It has recently been established that carotid bodies play a significant role in the regulation of activities of the cardiovascular system as well as in the pathogenesis of arterial hypertension, heart failure and diabetes. Aim of study was to determinate the influence of polymorphisms within genes of the renin-angiotensin-aldosterone system (RAAS) on the volume of the carotid bodies (CB) in patients with hypertension (HTA). The study group consisted of 77 patients with HTA. All patients were genotyped for single-nucleotide polymorphisms of genes coding for: angiotensinogen: rs4762, rs5049, rs5051 and rs699; angiotensin-converting enzyme: rs4343; angiotensin receptor type 1 gene (AGTR1): rs5182 and rs5186; and the aldosterone synthase: rs1799998. The estimation of volumes of CB (V rCB+lCB ) was based on computed tomography angiography. Among individuals with essential hypertension certain relationships were documented between rs5182 and rs5186 polymorphisms of AGTR1 gene and rs1799998 polymorphism of CYP11B2 gene on one hand and the volume of carotid bodies on one other. Patients carrying the C alleles within the rs5182 and rs5186 of AGTR1 gene was associated with higher values of V rCB+lCB . The carriage of the T allele in the rs5182 locus of the AGTR1 gene determine lower values of V rCB+lCB . In summary, in patients with HTA a higher volume of CB may be resulted from the presence of specific genotypes in RAAS., (Copyright © 2018 Elsevier B.V. All rights reserved.)