Od monoklonalnej gammapatii o nieokreślonym znaczeniu (MGUS) do szpiczaka plazmocytowego i amyloidozy — opis przypadku

We present a 69-year-old patient, in whom in March 2016 a monoclonal gammopathy of undeterminedsignificance (MGUS) was diagnosed. The disease was found during the diagnostics ofthrombocytopenia (from 2009 the number of platelets varied between 90–140 G/l). In serum immunofixationassay the presence of monoclonal IgG kappa protein was confirmed. In July 2017,when the patient presented with nephrotic syndrome and acute renal failure, 14.5% of plasmacells were found in the bone marrow. Moreover, a biopsy of abdominal fat revealed the presence ofamyloid composed of kappa light chains. The diagnosis of IgG kappa plasma cell myeloma (PCM)complicated with amyloidosis of the kidneys, heart, liver and spleen was established. The PCM progressioncomplicated with amyloidosis was very aggressive. Despite the treatment with bortezomiband dexamethasone the patient died early. Sudden deterioration of health (e.g. in the form of acute renal failure) in a patient with MGUS may indicate not only the progression of MGUS to PCM, butalso the development of amyloidosis, which is associated with turbulent disease and poor prognosis.Przedstawiono 69-letnią pacjentkę, u której w marcu 2016 roku stwierdzono monoklonalną gammapatię o nieokreślonym znaczeniu (MGUS). Chorobę rozpoznano w czasie diagnostyki występującej od 2009 roku małopłytkowości (liczba płytek krwi 90–140 G/l). W immunofikasacji surowicy stwierdzono obecność białka monoklonalnego IgG kappa. W lipcu 2017 roku u chorej stwierdzono zespół nerczycowy i ostrą niewydolność nerek, a w szpiku — 14,5% plazmocytów. Biopsja tkanki tłuszczowej z fałdu brzusznego wykazała obecność amyloidu z łańcuchów lekkich kappa. Rozpoznano szpiczaka plazmocytowego (PCM) IgG kappa powikłanego amyloidozą nerek, serca, wątroby oraz śledziony. Przebieg PCM powikłanego amyloidozą był bardzo agresywny; mimo zastosowanego leczenia bortezomibem i deksametazonem chora szybko zmarła. Nagłe pogorszenie się stanu zdrowia (np. w postaci ostrej niewydolności nerek) u chorego na MGUS może wskazywać nie tylko na progresję MGUS do PCM, ale także rozwój amyloidozy, co wiąże się z burzliwym przebiegiem choroby i złym rokowaniem

Niezwykłe współwystępowanie nietypowego guza przysadki wydzielającego TSH i przewlekłej białaczki limfatycznej

Thyrotropin-secreting adenomas (TSH-oma) are very rare pituitary tumours. They are macroadenomas usually presenting with signs and symptoms of hyperthyroidism, and mass effects. They can co-secrete other hormones such as growth hormone or prolactin. Different malignancies, including haematological ones, are reported in patients with pituitary diseases. Chronic lymphocytic leukemia (CLL) occurs mostly in older patients, more often in males. CLL is associated with increased risk of second malignancies such as other blood neoplasms, skin and solid tumours. We present a successful neurosurgical outcome in a patient with an interesting coincidence of atypical TSH-oma and asymptomatic CLL. (Endokrynol Pol 2014; 65 (2): 144–147)Gruczolaki wydzielające TSH (TSH-oma) są rzadkimi guzami przysadki. Zwykle są makrogruczolakami dającymi objawy nadczynności tarczycy i następstwa masy guza. Mogą wydzielać także inne hormony, jak hormon wzrostu czy prolaktynę. U chorych z chorobami przysadki występują inne nowotwory, także układu krwionośnego. Przewlekła białaczka limfatyczna (CLL) występuje głównie u osób w starszym wieku, częściej u mężczyzn. Występowanie CLL wiąże się ze zwiększonym zagrożeniem innymi nowotworami: krwi, skóry, guzami litymi. W pracy przedstawiono opis skutecznego leczenia neurochirurgicznego pacjenta z interesującym współwystępowaniem nietypowego guza przysadki wydzielającego TSH oraz chorującego na bezobjawową postać CLL. (Endokrynol Pol 2014; 65 (2): 144–147

Amyloidoza pierwotna AL z zajęciem serca

Amyloidozą (skrobiawicą) nazywa się całą grupę chorób, w których dochodzi do pozakomórkowegoodkładania się w tkankach nierozpuszczalnych białek nazywanych amyloidem. Amyloidozapierwotna AL powstaje w wyniku odkładania się łańcuchów lekkich immunoglobulin,co prowadzi do postępującej dysfunkcji narządów. Najczęściej dochodzi do zajęcia nerek,wątroby, śledziony, układu pokarmowego, nerwowego oraz serca. Zajęcie serca zazwyczajpowoduje niewydolność serca z zachowaną funkcją skurczową

Circulating sCD138 and Some Angiogenesis-Involved Cytokines Help to Anticipate the Disease Progression of Early-Stage B-Cell Chronic Lymphocytic Leukemia

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

Variations in Suppressor Molecule CTLA-4 Gene Are Related to Susceptibility to Multiple Myeloma in a Polish Population

Various phenotype and functional T-cell abnormalities are observed in multiple myeloma (MM) patients. The aim of this study was to investigate the association between polymorphisms in the gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of the T-lymphocyte immune response and susceptibility to multiple myeloma in a Polish population. Two hundred MM patients and 380 healthy subjects were genotyped for the following polymorphisms: CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CT60 (CTLA-4g.*6230G>A), Jo31 (CTLA-4g.*10223G>T). Our study is the largest and most comprehensive evaluation to date of the association between genetic polymorphisms in the CTLA-4 molecule and multiple myeloma. It was found that CTLA-4c.49A>G[G], CT60[G], and Jo31[G] alleles were more frequently observed in MM patients than in controls (0.50 vs. 0.44, p = 0.03, 0.65 vs. 0.58, p = 0.04, and 0.63 vs. 0.57, p = 0.03, respectively). Moreover, the haplotype CTLA-4c.49A>G[G], CTLA-4g.319C>T[C], CTLA-4g.*642AT(8_33) [8], CT60[G], Jo31[G] including all susceptibility alleles increases the risk of MM about fourfold (OR: 3.79, 95%CI: 2.08–6.89, p = 0.00001). These findings indicate that genetic variations in the CTLA-4 gene play role in susceptibility to multiple myeloma and warrant further investigation through replication studies

Curcumin Loaded Nanocarriers with Varying Charges Augmented with Electroporation Designed for Colon Cancer Therapy

(1) Background: The size and surface charge are the most significant parameters of nanocarriers that determine their efficiency and potential application. The poor cell uptake of encapsulated drugs is the main limitation in anticancer treatment. The well-defined properties of nanocarriers will enable to target specific tissue and deliver an active cargo. (2) Methods: In the current study, poly(D,L -lactide) (PLA) nanocarriers loaded with curcumin (CUR) and differing surface charge were evaluated for transport efficacy in combination with electroporation (EP) in dependence on the type of cells. The obtained CUR-loaded nanoparticles with diameters ranging from 195 to 334 nm (derived from dynamic light scattering (DLS)) were characterized by atomic force microscopy (AFM) (morphology and shape) and Doppler electrophoresis (ζ-potential) as well as UV-vis spectroscopy (CUR encapsulation efficiency (about 90%) and photobleaching rate). The drug delivery properties of the obtained PLA nanocarriers enhanced by electroporation were assessed in human colon cancer cells (LoVo), excitable normal rat muscle cells (L6), and free of voltage-gated ion channels cells (CHO-K1). CLSM studies, viability, and ROS release were performed to determine the biological effects of nanocarriers. (3) Results: The highest photodynamic activity indicated anionic nanocarriers (1a) stabilized by C12(COONa)2 surfactant. Nanocarriers were cytotoxic for LoVo cells and less cytotoxic for normal cells. ROS release increased in cancer cells with the increasing electric field intensity, irradiation, and time after EP. Muscle L6 cells were less sensitive to electric pulses. (4) Conclusions: EP stimulation for CUR-PLA nanocarriers transport was considered to improve the regulated and more effective delivery of nanosystems differing in surface charge

Fluorescent Activity-Based Probe To Image and Inhibit Factor XIa Activity in Human Plasma.

Funder: European Regional Development FundAnticoagulation therapy is a mainstay of the treatment of thrombotic disorders; however, conventional anticoagulants trade antithrombotic benefits for bleeding risk. Factor (f) XI deficiency, known as hemophilia C, rarely causes spontaneous bleeding, suggesting that fXI plays a limited role in hemostasis. In contrast, individuals with congenital fXI deficiency display a reduced incidence of ischemic stroke and venous thromboembolism, indicating that fXI plays a role in thrombosis. For these reasons, there is intense interest in pursuing fXI/factor XIa (fXIa) as targets for achieving antithrombotic benefit with reduced bleeding risk. To obtain selective inhibitors of fXIa, we employed libraries of natural and unnatural amino acids to profile fXIa substrate preferences. We developed chemical tools for investigating fXIa activity, such as substrates, inhibitors, and activity-based probes (ABPs). Finally, we demonstrated that our ABP selectively labels fXIa in the human plasma, making this tool suitable for further studies on the role of fXIa in biological samples

St. Thomas Modified Cardioplegia Effects on Myoblasts’ Viability and Morphology

Background and Objectives: The cardioplegic arrest of the heart during cardiosurgical procedures is the crucial element of a cardioprotection strategy. Numerous clinical trials compare different cardioplegic solutions and cardioprotective protocols, but a relatively small number of papers apply to in vitro conditions using cultured cells. This work aimed to analyze whether it is possible to use the rat heart myocardium cells as an in vitro model to study the protective properties of St. Thomas cardioplegia (ST2C). Methods: The rat heart myocardium cells-H9C2 were incubated with cold cardioplegia for up to 24 h. After incubation, we determined: viability, confluency, and cell size, the thiol groups’ level by modifying Ellman’s method, Ki67, and Proliferating Cell Nuclear Antigen expression (PCNA). The impact on cells’ morphology was visualized by the ultrastructural (TEM) study and holotomograpic 3D imaging. Results: The viability and confluency analysis demonstrated that the safest exposure to ST2C, should not exceed 4h. An increased expression of Ki67 antigen and PCNA was observed. TEM and 3D imaging studies revealed vacuolization after the longest period of exposure (24). Conclusions: According to obtained results, we conclude that STC can play a protective role in cardiac surgery during heart arrest