Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in amyotrophic lateral sclerosis (ALS)

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, responsible for the integrity of the basement membrane (BM) via degradation of extracellular matrix and BM components. These enzymes are presented in central and peripheral nervous system. They are considered to be involved in the pathogenesis of several neurological diseases, including amyotrophic lateral sclerosis (ALS). ALS is a motor neuron disease, leading to muscle atrophy, paralysis and death within 3–5 years from diagnosis. Currently, there is no treatment that can substantially prolong life of ALS patients. Despite the fact that MMPs are not specific for ALS, there is also strong evidence that these enzymes are involved in the pathology of ALS. MMPs are able to exert direct neurotoxic effects, or may cause cell death by degrading matrix proteins. The objective of this paper is to provide an updated and comprehensive review concerning the role of MMPs and their tissue inhibitors (TIMPs) in the pathology of ALS with an emphasis on the significance of MMP-2 and MMP-9 as well as their tissue inhibitors as potential biomarkers of ALS. Numerous hypotheses have been proposed regarding the role of selected MMPs and TIMPs in ALS pathogenesis. Moreover, selective MMPs’ inhibitors might be potential targets for therapeutic strategies for patients with ALS. However, future investigations are necessary before some of those non-specific for ALS enzymes could finally be used as biomarkers of this disease

The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer

Esophageal cancer (EC) is one of the most aggressive malignant tumors of the gastrointestinal tract. There are two distinct histological types of EC: esophageal squamous cell carcinoma and adenocarcinoma of the esophagus. Etiologic factors and the patterns of incidence of both subtypes are different. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in esophageal carcinogenesis. Gellatinases MMP-2 and MMP-9 are able to degrade collagen IV from basement membranes and extracellular matrix which is related to tumor progression, including invasion, metastasis, growth and angiogenesis. It has been shown that increased expression of MMPs plays a crucial role in the development of several human malignancies, including esophageal cancer. The activity of MMPs is regulated by their endogenous natural inhibitors (TIMPs). Among these, the roles of TIMP-1 and TIMP-2 in EC development, tumor progression and formation of metastases have been most extensively characterized and best recognized

Niektóre problemy związane z oznaczaniem testosteronu

Testosterone is the main male sex hormone which determination is useful for assessment of androgen status. It seems that serum levels of testosterone, when assayed by commonly used methods, do not correlate with clinical parameters. One of the causes may be that these assays are suitable for determination of total testosterone, but not for measurement of biologically active forms of this hormone. The aim of this review is to present usefulness of testosterone measurement and its bioactive forms determination as well as factors influencing on their levels.Testosteron jest głównym męskim hormonem płciowym, którego oznaczanie ma istotne znaczenie do oceny stopnia androgenizacji w różnych stanach chorobowych. W powszechnym odczuciu lekarzy praktyków stężenie tego hormonu, oznaczane dostępnymi metodami, nie zawsze koreluje z parametrami klinicznymi. Jedną z przyczyn takiego stanu rzeczy jest fakt, że wyżej wymienione metody diagnostyczne pozwalają na oznaczanie głównie testosteronu całkowitego, nie dają zaś informacji o stężeniu aktywnej biologicznie frakcji tego hormonu. W niniejszej pracy przedstawiono celowość i metody oznaczania testosteronu oraz jego frakcji, jak również czynniki wpływające na wyniki tych oznaczeń. (Endokrynol Pol 2007; 58 (5): 440-445

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients.

The aim of the study was to assess the importance of the measurement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC) in relation to clinicopathological features of tumor and patients' survival. Additionally, we determined serum MMP-2 and TIMP-2 in colorectal adenoma (CA) patients and healthy controls and compared them with tumor markers, CEA and CA 19-9. The serum levels of MMP-2 and TIMP-2 in 91 CRC patients, 28 CA subjects and 91 healthy controls were determined by ELISA method, but concentrations of CEA and CA 19-9 using MEIA method. Nonparametric statistical analyses were used. Serum levels of MMP-2 and TIMP-2 were significantly lower in CRC patients than in healthy subjects and decreased with tumor stage. Additionally, MMP-2 concentrations were significantly lower in patients with CRC than in CA group. Diagnostic sensitivity of TIMP-2 (59%) was the highest among biomarkers tested and increased in combined use with CEA (79%). Moreover, the area under ROC curve (AUC) of TIMP-2 was larger than AUC of MMP-2 in differentiation between CRC and healthy subjects, but lower than AUC of matrix metalloproteinase 2 in differentiation between colorectal cancer and adenoma. Our findings suggest clinical usefulness of TIMP-2 as a biomarker in the diagnosis of CRC, especially in combination with CEA. However, further investigation is necessary

Clinical significance of serum levels of matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in gastric cancer

Matrix metalloproteinase 2 (MMP-2) is able to degrade type IV collagen, and thus plays a key role in the migration of tumor cells. MMP-2 activity is inhibited by its tissue inhibitor (TIMP-2). The imbalance between MMPs and TIMPs may facilitate progression of cancer cells. The aim of this study was to compare the clinical importance of MMP-2 and TIMP-2 to that of classical tumor markers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in the diagnosis of gastric cancer (GC) by calculating the diagnostic criteria and estimating the levels of MMP-2, TIMP-2, CEA and CA 19-9 in GC patients in relation to clinicopathological features of cancer. We found that serum levels of MMP-2 and TIMP-2 were significantly lower, whereas serum tumor markers were higher, in GC patients than in healthy subjects. Moreover, concentrations of TIMP-2 and CEA correlated with gastric wall infiltration, while CA 19-9 levels correlated with gastric wall infiltration and the presence of nodal metastasis. None of the proteins tested was found to be an independent prognostic factor for GC patients’ survival. The percentage of true positive results of TIMP-2 (61%) was higher than those of MMP-2 (54%) and the classical tumor markers CEA (21%) and CA 19-9 (31%). The highest diagnostic sensitivity was observed for the combined use of TIMP-2 with MMP-2 (77%). The results suggest the greater importance of serum MMP-2 and TIMP-2 than of the classical tumor markers CEA and CA 19-9 in the diagnosis of GC. But this issue requires further investigation. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 125–131

Korelacje pomiędzy stężeniami biomarkerów w płynie mózgowo-rdzeniowym a nasileniem zaburzeń funkcji poznawczych w chorobie Alzheimera

Introduction. Alzheimer’s disease (AD) is a progressive, neurodegenerative disease and the most common cause of dementia.Aim. The aim of the study was to assess the concentration of the 42 amino acid isoform of Aβ (Aβ1-42), Aβ1-42/Aβ1-40 (42 amino acid isoform of Aβ/40 amino acid isoform of Aβ) ratio, Tau and hyperphosphorylated Tau (pTau) protein in cerebrospinal fluid (CSF) of patients diagnosed with Alzheimer disease (AD) and to compare their correlations with degree of cognitive impairment assessed with Mini Mental State Examination (MMSE).Material and Methods. In this study, using the ELISA immunoassay standard kits, we measured the average concentration of Aβ1-42, Aβ1-42/Aβ1-40 ratio, Tau and pTau protein, in the CSF obtained from subjects diagnosed with Alzheimer’s disease (n=20, 13 women and 7 men, mean age 69.9±10.4). The cognitive functions of the patients were assessed with MMSE test. The correlations between concentration of CSF biomarkers and degree of cognitive impairment were measured using nonparametric Spearman rank correlation coefficient.Results. Our results showed negative correlation between concentration of Tau protein in CSF and the number of points scored in MMSE test (r=-0.45; p=0.046). There was no correlation between a degree of cognitive impairment assessed with MMSE test and concentration of pTau (r=-0.42; p=0.066), Aβ1-42 (r=0.02; p=0.927), and Aβ1-42/Aβ1-40 ratio (r=-0.07; p=0.775). There was also positive correlation between concentration of Aβ1-42 and Aβ1-42/Aβ1-40 ratio (r=0.91; p<0.0001), and between concentration of Tau and pTau (r=0.94; p<0.0001).Conclusions. Tau protein plays not only a crucial role in the early diagnostics, but also reflects the intensity of cognitive impairment in course of Alzheimer disease. (JNNN 2018;7(4):150–154)Wstęp. Choroba Alzheimera (AD) jest postępującą chorobą neurodegeneracyjną i najczęstszą przyczyną otępienia.Cel. Celem pracy była ocena stężenia 42 aminokwasowego Aβ1 (Aβ1-42), współczynnika 42 aminokwasowego Aβ1/40 aminokwasowego Aβ1 (Aβ1-42/Aβ1-40), białka Tau i nadmiernie ufosforylowanej formy białka Tau (pTau) w płynie mózgowo-rdzeniowym (PMR) pacjentów z rozpoznaną chorobą Alzheimera (AD) oraz porównanie ich stężenia ze stopniem zaburzeń funkcji poznawczych ocenianych przy pomocy krótkiej skali oceny stanu psychicznego (MMSE).Materiał i metody. W badaniu, przy użyciu standardowych zestawów testów immunologicznych ELISA, oznaczono średnie stężenie Aβ1-42, współczynnika Aβ1-42/Aβ1-40, białka Tau i pTau w PMR pobranym od pacjentów z rozpoznaną chorobą Alzheimera (n=20, 13 kobiet i 7 mężczyzn, średnia wieku 69,9±10,4 lat). Funkcje poznawcze pacjentów oceniano przy pomocy testu MMSE. Korelacje pomiędzy stężeniem biomarkerów w PMR a stopniem upośledzenia funkcji poznawczych były mierzone za pomocą nieparametrycznego współczynnika Spearmana.Wyniki. Otrzymane wyniki wykazały negatywną korelację pomiędzy stężeniem białka Tau w PMR oraz liczbą punktów uzyskanych w skali MMSE (r=-0,45; p=0,046). Nie stwierdzono korelacji pomiędzy stopniem nasilenia zaburzeń funkcji poznawczych ocenianych w teście MMSE a stężeniem pTau (r=-0,42; p=0,066), Aβ1-42 (r=0,02; p=0,927) oraz współczynnika Aβ1-42/Aβ1-40 (r=-0,07; p=0,775). Stwierdzono również pozytywną korelację pomiędzy stężeniem Aβ1-42 i współczynnikiem Aβ1-42/Aβ1-40 (r=0,91; p<0,0001) oraz pomiędzy białkiem Tau i pTau (r=0,94; p<0,0001).Wnioski. Białko Tau odgrywa nie tylko kluczową rolę we wczesnej diagnostyce, ale również odzwierciedla nasilenie zaburzeń funkcji poznawczych w przebiegu choroby Alzheimera. (PNN 2018;7(4):150–154

The impact of laparoscopic adrenalectomy on renal function. Results of a prospective randomised clinical trial

Introduction: Laparoscopic adrenalectomy is the gold standard management of benign adrenal masses and isolated metastases to adrenal glands. Two techniques of endoscopic adrenalectomy: lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) seem to be equally safe and effective. Recent studies suggest advantages of PRA over LTA in terms of lower intensity of postoperative pain, shorter hospital stay, faster recovery, and lower early morbidity. However, PRA involves high insufflation pressure of CO2 within a limited retroperitoneal space. The aim of our study was to prospectively assess the effect of LTA versus PRA laparoscopic adrenalectomies on renal function. Material and methods: We randomly assigned patients referred for unilateral adrenalectomy to either LTA (n = 33) or PRA (n = 44). The inclusion criteria were: hormonal activity and/or tumour diameter > 4 cm and/or suspicion of metastasis to adrenal gland. The exclusion criteria comprised: tumours > 8 cm, results of imaging studies suggesting primary invasive malignancy, and refusal to undergo randomisation. The patients were prospectively followed for a minimum of six months. Serum creatinine, cystatin C, and urinary neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively and at postoperative days: 1, 7, and 30. Results: We found increased concentrations of urinary NGAL at day 1 following laparoscopic adrenalectomy using PRA, as compared to LTA. Patients undergoing right-sided PRA had increased creatinine concentrations, as compared to left-sided PRA. Patients with aldosterone-producing adenoma had decreased preoperative eGFR as compared to subjects with non-functioning incidentaloma. NGAL increased significantly in this group postoperatively. All the disturbances normalised within one month postoperatively. Conclusions: Renal function impairment after PRA may result from compression of inferior vena cava by high retroperitoneal pressure during right-sided adrenalectomy. Despite the transient character of the observed abnormalities, we suggest that patients with high risk of acute kidney injury may benefit from an alternative technique of adrenalectomy using LTA

The concentration of kynurenine in rat model of asthma.

Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN). To study the immunological system regulation in asthma a simple and sensitive models of asthma are required. In the present study we induced rat model of asthma using ovalbumin (OVA) sensitization followed by challenge with OVA. The development of asthma has been confirmed by plasma total IgE measurement and the histological examination. The concentration of KYN has been determined in plasma, lungs and liver by high-performance liquid chromatography (HPLC). In OVA sensitized rats the concentration of total IgE was statistically significantly increased as compared to VEH sensitized control groups (437.6 +/- 97.7 kU/l vs 159.2 +/- 22.7 kU/l, respectively; p< 0.01). In asthmatic animals, the number of eosinophils, neutrophils and mast cells increased considerably, and epithelial lesion and the increase in airway epithelium goblet cells and edema of bronchial mucosa were present. We did not observe any significant changes in the concentration of KYN in plasma, lungs or liver between studied groups. In conclusion, the concentration of KYN remains unchanged in asthmatic animals as compared to control groups. Further studies using rat model of asthma are warranted to establish the role of kynurenine pathway regulation in asthma