Dynamic Properties of Skeletal Muscle Contraction in Rats with Diabetes

The study was conducted on 20 white nonlinear male rats, which were divided into 2 groups of 10 animals each. Rats in the first group were used as control. Rats in the second group were induced type I diabetes by intraperitoneal (i.p.) administration of streptozotocin (65 mg/kg). Diabetes in rats was confirmed by the presence of hyperglycemia. For the establishment of nociceptive pain sensation, mechanical nociceptive test and tail-flick test were conducted in rats. Further animals were anesthetized by i.p. administration of Nembutal (40 mg/kg). The study of dynamic properties of muscle contraction was performed under conditions of the tibia muscle activation by using the modulated stimulation of efferent n. tibialis. Streptozotocin (STZ) was injected in rats; as a result, the blood glucose level was increased by 4.4 times (p ≤ 0.001). Pain sensitivity in diabetic rats was suppressed, indicating the development of peripheral neuropathy. In rats with diabetes, biomechanical parameters of tibia muscle contraction such as the maximum force of contraction, the speed of maximum force of contraction, the retention time of maximum force of contraction and integrated power of muscle contraction (it is calculated on the total area of the received force curves) were violated. This prevents adequate implementation motor neuron pools muscular system, which will have significant consequences in accurate positional movements

Wpływ Z56822977 na biosyntezę serotoniny w mózgu szczurów z otyłością wywołaną przez podawanie glutaminianu sodu

Wstęp: Badanie przeprowadzono w celu wyjaśnienia wpływu Z56822977 na biosyntezę serotoniny w mózgu szczurów z otyłością wy­wołaną podawaniem glutaminianu sodu (monosodium glutamate, MSG). Materiał i metody: W badaniu wykorzystano 18 samców szczura. Zwierzęta podzielono na trzy grupy: 1 — grupa kontrolna, 2 — grupa MSG, 3 — grupa MSG + Z56822977. Szczurzym oseskom w grupie 2 i 3 podawano podskórnie MSG rozpuszczony w soli fizjologicznej w dawce 4 mg/g masy ciała w objętości 8 μl/g w 2., 4., 6., 8. i 10. dniu życia. Grupie 3 podawano doustnie wodny roztwór Z56822977 w dawce 25 mg/kg w objętości 1 ml/kg. Pierwszą dawkę Z56822977 podawano po ukończeniu 4 tygodni życia, a następnie kontynuowa­no podawanie badanej substancji cyklicznie wedlug schematu tydzień podawania substancji badanej/3 tygodnie przerwy. Zwierzętom z grupy MSG podawano odpowiednio 1 ml/kg wody doustnie. Przez pierwsze 4 miesiące życia szczury otrzymywały standardową karmę. Zmierzono zawartość serotoniny, tryptofanu i 5-hydroksytryptofanu (5-HTr) oraz aktywność hydroksylazy tryptofanowej (tryptophan hydroxylase, TRH), dekarboksylazy aminokwasów (amino acid decarboxylase, AADC) i monoaminooksydazy (MAO) w tkance mózgowej. Wyniki: Wykazano, że podawanie Z56822977 ma pozytywny wpływ na główne wskaźniki otyłości, co odzwierciedlają zmiany podsta­wowych parametrów fizjologicznych i biochemicznych [zmniejszenie masy ciała o 13% vs. MSG (p < 0,05); zmniejszenie wskaźnika masy ciała (body mass index, BMI), wskaźnika Lee oraz masy tkanki tłuszczowej trzewnej odpowiednio o 18%, 7% i 55%, (p < 0,05) w porównaniu z grupą MSG]. Zawartość tryptofanu i serotoniny była istotnie niższa (p < 0,05) u szczurów z otyłością wywołaną przez MSG. W badaniach wykazano, że u otyłych szczurów aktywność MAO zwiększa się o 97% (p < 0,05), a aktywność TRH i AADC odpowiednio o 44% i 53% (p < 0,05). Podawanie Z56822977 powodowało zwiększenie zawartości serotoniny i tryptofanu w mózgach szczurów i przywracało poziom aktywności enzymów (MAO, TRH, AADC) do wartości mierzonych u zwierząt kontrolnych. Wnioski: Wiadomo, że otyłość wiąże się z zaburzeniem syntezy serotoniny w mózgu szczurów. Jednak podawanie Z56822977 prowadzi do normalizacji stężenia serotoniny i tryptofanu oraz przywrócenia prawidłowej aktywności enzymów uczestniczących w biosynte­zie i degradacji serotoniny. Podawanie Z56822977, cząsteczki wpływającej na układ serotoninergiczny, może powodować korzystne efekty w leczeniu otyłości wywołanej przez MSG u szczurów. Można rozważać zastosowanie cząsteczki Z56822977 jako nowego leku stosowanego w otyłości, jednak konieczne są dalsze badania w celu potwierdzenia jej działania

Evaluation of proteolytic activity and serine proteases distribution in plasma from patients with bladder cancer

BackgroundBladder cancer (BC) is an aggressive disease with a poor prognosis. A bladder tumor, like other malignant neoplasms, is characterized by the presence of both cancer cells and stromal cells which secrete cytokines, chemokines, growth factors, and proteolytic enzymes. One such class of proteolytic enzymes are serine proteases, which take part in the tumor microenvironment formation via supporting and contributing to tumor progression. This study aims to evaluate the proteolytic activity and serine protease contribution in plasma from BC patients.MethodsThe research involved patients of Alexandrovsky city clinical hospital aged 52–76 with transitional cell carcinoma of the bladder. All examined patients were divided into five groups: the control group included conditionally healthy donors, while other patients were grouped according to their tumor stage (I, II, III and IV). Plasma plasminogen levels were determined by enzyme-linked immunosorbent assay, and the potential activity was measured by chromogenic plasminogen assay. Serine proteases fractions were obtained by the affinity chromatography method, and enzyme concentration in the selected fractions were determined by the Bradford method. Serine proteases distribution was investigated by electrophoresis in a polyacrylamide gel.ResultsIt was determined that the concentration, potential activity of plasminogen, and the total amount of serine proteases in plasma from BC patients were greater than the values of the corresponding indicators in healthy donors. This could be one of the factors contributing to increased proteolysis seen in the process of carcinogenesis. Plasminogen concentration in BC patients with stage IV disease; however, displayed a tendency to be reduced compared to earlier stages, and the potential activity of plasminogen was significantly lower in patients with stages III – IV BC. Futhermore, a tumor stage specific gradual decline in the serine protease plasma content was shown. The results of electrophoretic analysis established a significant diminishment in the percentage of high molecular weight components (under non-reducing conditions) and their complete disappearance (under reducing conditions) in plasma serine protease fractions from BC patients. A decline in the percentage of heavy and light plasmin chains in BC patients was also observed. Additionally, a rise in the degraded forms of plasminogen/plasmin content was seen in BC samples, as well as the presence of fractions corresponding to trypsin and NE (under non-reducing conditions) that were absent in the control samples.ConclusionThe results indicate significant changes in the proteolytic activity of plasma, from BC patients when compared to healthy controls, which is accompanied by alterations in serine protease distribution caused by tumor microenvironment pecularlities at the different stages of oncopathology

The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity.

Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E. coli, Clostridium, Staphylococcus spp. and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1α and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-α and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development

Structure−Activity Relationships of Photoswitchable Diarylethene- Based β‑Hairpin Peptides as Membranolytic Antimicrobial and Anticancer Agents

Five series (28 structures) of photoswitchable β-hairpin peptides were synthesized based on the cyclic scaffold of the natural antibiotic gramicidin S. Cell-type selectivity was compared for all activated (diarylethene “ringopen”) and deactivated (“ring-closed”) forms in terms of antibacterial activity (MIC against Escherichia coli and Bacillus subtilis), anticancer activity (IC50 against HeLa cell line), and hemolytic cytotoxicity (HC50 against human erythrocytes). Correlations between the conformational plasticity of the peptides, their hydrophobicity, and their bioactivity were also analyzed. Considerable improvements in selectivity were achieved compared to the reference compound. We found a dissociation of the anticancer activity from hemolysis. Phototherapeutic indices (PTI), HC50(closed)/MIC(open) and HC50(closed)/IC50(open), were introduced for the peptides as safety criteria. The highest PTI for HeLa-selective toxicity were observed among analogues containing hydroxyleucine on the hydrophobic face. For one compound, high PTIs were demonstrated across a range of different cancer cell lines, including a doxorubicin-resistant on

The correction of the metabolic parameters of msg-induced obesity in rats by 2-[4-(benzyloxy) phenoxy] acetic acid

Epidemiological data showed that the number of obese people increases swiftly in all countries. Obesity can evoke metabolic syndrome or second type diabetes (T2D). So, the aim of our study was to investigate the influence of 2-[4-(benzyloxy) phenoxy] acetic acid on metabolic parameters of monosodium glutamate (MSG)-induced obesity in rats. We divided the rats as follows: 1- control group, 2 - MSG-group, 3 - MSG + 2-[4-(benzyloxy) phenoxy] acetic acid group. We investigated anthropometric parameters and blood biochemistry. It was established that MSG induced the development of visceral obesity in rats, in particular, it increased the Lee index, body mass index, deposits of subcutaneous, gonadal and visceral adipose tissue. The administration of 2-[4-(benzyloxy) phenoxy] acetic acid decreased metabolic parameters evoked by MSG. After obesity induction, there was recorded significant growth of cholesterol, triglycerides, and LDL cholesterol blood levels and significant decline in HDL cholesterol blood levels. There was a significant reduction in triglycerides, LDL cholesterol and VLDL, in 2-[4-(benzyloxy) phenoxy] acetic acid - treated group. Our results represent the basis for development of new treatment of obesity and associated conditions