Protection of Azidothymidine-Induced Cardiopathology in Mice by Mildronate, a Mitochondria-Targeted Drug

Azidothymidine, a nucleoside-analogue reverse transcriptase inhibitor (NRTI), is a commonly used antiretroviral drug in AIDS treatment, however its use is limited by severe toxic side effects due to its influence on mitochondria that result in myopathy, particularly affecting the cardiac muscle. We suggest that effective protection of azidothymidine- induced cardiopathology can be expected from drugs that are capable of targeting mitochondria. Therefore the present study in mice was carried out with mildronate, a cardioprotective drug of the aza-butyrobetaine class, which previously has been shown to act as a highly potent protector of mitochondrial processes. In our study, saline (control)…

CD9a expression in premalignant lesions, gastric and colorectal carcinoma

P5

Background Pathogenic action of nitric oxide (NO) is responsible to a large extent for development of complications of the diabetes mellitus (DM). NO overproduction is largerly responsible for development of diabetic nephropathy. Thus search for compounds modifying NO production appears to be important for development of pharmacological remedies for treatment of DM complications. Dihydropiridines (DHP) appear to be prospective compounds from this point of view. The goal of the present work was to study alterations of NO production in streptozotocin model of DM in rats and ability of several DHPs and to normalize NO synthesis in kidneys of these animals. Methods Diabetes mellitus was induced…

Effects of an Antimutagenic 1,4-Dihydropyridine AV-153 on Expression of Nitric Oxide Synthases and DNA Repair-related Enzymes and Genes in Kidneys of Rats with a Streptozotocin Model of Diabetes Mellitus.

Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry. Development of DM significantly induced PARP1 protein express…

Abstract 4246: Associations of Epstein-Barr virus (EBV)-positive gastric cancer with circulating mediators of inflammation and immune response

Abstract Epstein-Barr virus (EBV) positivity defines one of four major molecular types of gastric cancer in The Cancer Genome Atlas (TCGA). However, viral status is not routinely determined in clinical practice and tumor samples are not generally collected in epidemiologic research. Histologically, EBV-positive gastric cancer is characterized by prominent inflammatory infiltrate. In molecular analyses from TCGA, EBV-positive gastric cancer had significantly higher expression of several chemokines, chemokine receptors and programmed death-ligand 1 (PD-L1) as compared to other molecular types combined. We hypothesized that EBV tumor status may also be reflected in profiles of circulating chem…

Increased numbers of CD4 and CD8 positive T lymphocytes with decreased CD4/CD8 ratio in patients with high grade CIN lesions

Lack of Association Between Rs2067474 Polymorphism in the Histamine Receptor H2 Gene and Gastric Cancer In Latvian Population

Abstract Histamine has an important role in the process of the gastric mucosa inflammation acting via histamine receptor H2 (encoded by the gene HRH2). Single nucleotide polymorphism of the enhancer element of HRH2 gene promoter rs2067474 (1018G>A)may be associated with changes of expression of the receptor. We attempted to clarify the association of this polymorphism with gastric cancer and/or atrophic gastritis in the Latvian (Caucasian) population. The study group consisted of 121 gastric cancer patients and 650 patients with no evidence of gastric neoplasia on upper gastrointestinal endoscopy. Genotyping for rs2067474 was performed with the TaqMan probe-based system using a commercia…

Erratum: Melanoma Unknown Primary Brain Metastasis Treatment With ECHO-7 Oncolytic Virus Rigvir: A Case Report

Melanoma is considered an aggressive malignancy with a tendency of forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of the disease. Melanoma brain metastases have many severe side effects and, unfortunately, any disease related to the brain has limited therapeutic options due to the blood–brain barrier. The course of the disease after a treatment course is complicated to predict, and it is difficult to obtain long-lasting remission. In this report, we describe a female patient with unknown primary melanoma brain metasta…

New 1,4-Dihydropyridines Down-regulate Nitric Oxide in Animals with Streptozotocin-induced Diabetes Mellitus and Protect Deoxyribonucleic Acid against Peroxynitrite Action.

Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic actions of nitric oxide (NO) are responsible to a large extent for development of complications of DM. Search for compounds regulating NO production in patients with DM is thus important for the development of pharmacological drugs. Dihydropyridines (1,4-DHPs) are prospective compounds from this point of view. The goals of this study were to study the in vivo effects of new DHPs on NO and reactive nitrogen and oxygen species production in a streptozotocin (STZ)-induced model of DM in rats and to study their ability to protect DNA against nocive action of peroxynitrite. STZ…

Effects of Kaempferol and Myricetin on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Rats

Abstract:  When administered as drugs or consumed as food components, polyphenolic compounds synthesized in plants interfere with intracellular signal transduction pathways, including pathways of nitric oxide synthase expression. However, effects of these compounds in vivo do not always correlate with nitric oxide synthase-inhibiting activities revealed in experiments with cultured cells. The initial goal of this work was to compare effects of flavonoids kaempferol and myricetin on inducible nitric oxide synthase mRNA and protein expression monitored by real-time RT-PCR and immunohistochemistry and to evaluate the impact of these effects on nitric oxide production in rat organs measured by …

Mildronate enhances learning/memory and changes hippocampal protein expression in trained rats.

Previously we demonstrated that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a representative of the aza-butyrobetaine class of compounds, protects mitochondrial metabolism under conditions such as ischemia. Mildronate also acted as a neuroprotective agent in an azidothymidine-induced mouse model of neurotoxicity, as well as in a rat model of Parkinson's disease. These observations suggest that mildronate may stimulate processes involved in cell survival and change expression of proteins involved in neurogenic processes. The present study investigated the influence of mildronate on learning and memory in the passive avoidance response (PAR) test and the active condition…

Multicentric randomised study ofHelicobacter pylorieradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study

IntroductionPopulation-based eradication ofHelicobacter pylorihas been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whetherH pylorieradication combined with pepsinogen testing reduces mortality from gastric cancer among 40–64-year-old individuals. The secondary objectives include evaluat…

Non-Invasive Diagnosis of Gastroesophageal Reflux Disease Using Gastrin- and Pepsinogen-Based Tests

Abstract Gastrin-17 (G-17), pepsinogen-1 (Pg1) and pepsinogen-2 (Pg2) reflect the functional state of gastric mucosa and are used for non-invasive diagnosis and screening of atrophic gastritis. The aim of the study was to clarify if erosive reflux disease (ERD) or non-ERD (NERD) can be distinguished from other dyspeptic conditions in patients, in a non-invasive manner using specific biomarkers. Levels of G-17, Pg1, and Pg2 were measured in 141 ERD patients (median age 48 years, males — 68), 122 NERD patients (median age 45 years, males — 32) and 410 control patients (median age 50 years, males — 97). Levels of biomarkers in ERD and NERD groups were compared to controls. Median levels of G-1…

“New Kids on the Block” — The Game Changers. The Role of Immune Check Point Blockade in Personalised Treatment of Prostate, Urinary Bladder and Kidney Cancer

Abstract Early detection and diagnosis of cancer followed by a personalised approach to treatment is a key and can save lives. It has been an important issue in both the medical and social fields. The search for instruments and/or diagnostics tools able to detect cancers at an early stage has led to consideration of the usage of various approaches, such as exhaled air, biomarkers in blood, urine testing as well as imaging techniques. This actual time and everything that is happening around us could be characterised as a strange and very unpredictable time. This comparison could be made not only due to the actual coronavirus situation, but also the same can be noticed in the personalised med…

Influence of metformin on GLUT1 gene and protein expression in rat streptozotocindiabetes mellitusmodel

Metformin improves hyperglycaemia via mechanisms which include activation of AMP-activated protein kinase (AMPK). Recent findings indicate that some metabolic actions of metformin occur also by AMPK-independent mechanisms.To study the action of metformin on expression of GLUT1 glucose transporter in rat streptozotocin model of diabetes mellitus.Streptozotocin-induced rats were treated with metformin while monitoring parameters of carbohydrate and lipid metabolism. GLUT1 mRNA and protein expression in kidneys, heart, liver and muscles were studied by means of real time quantitative RT-PCR and immunohistochemistry correspondingly.Metformin treatment decreased glucose concentration, glycated h…

Adrenal Gland and Gastric Malignant Melanoma without Evidence of Skin Lesion Treated with the Oncolytic Virus Rigvir

Adrenal gland melanoma is an extremely rare diagnosis with less than 20 cases reported. The criteria for diagnosing adrenal gland melanoma include involvement of only one adrenal gland, presence of melanin pigment in the histological examination of the tumor tissue, no primary melanoma tumor in any other organ, and no history of resection of pigmented lesions. However, it is complicated to rule out melanoma of unknown primary origin. Here we report a female patient who at the age of 75 years was admitted to hospital due to suspicion of adrenal and gastric tumor. The largest tumor was found in the adrenal gland, thus leading to the diagnosis of primary adrenal gland melanoma presenting metas…

Accuracy of two plasma antibody tests and faecal antigen test for non-invasive detection of H. pylori in middle-aged Caucasian general population sample.

The aim of the study was to assess the accuracy of two plasma Helicobacter pylori (H. pylori) antibody test-systems and a stool antigen test (SAT) system in a general population sample in Latvia.Blood and faecal samples were analysed in healthy individuals (40-64 years), referred for upper gastrointestinal endoscopy according to pilot study protocol within a population-based study investigating gastric cancer prevention strategies (GISTAR pilot study). Antibodies to H. pylori were assessed in plasma by latex-agglutination test and enzyme-linked immunosorbent assay (ELISA). H. pylori antigen in faecal samples was detected by a monoclonal enzyme immunoassay-based SAT. Histological assessment …

Sa1459 FICE Endoscopy Diagnostic Accuracy by Applying OLGA and OLGIM Systems

Increased sirtuin expression in patient with lung squamous cell carcinoma co-morbid with COPD

Background: COPD is frequently associated with comorbidities, the most serious and prevalent include lung cancer. Sirtuin 1 (SIRT1) is known to deacetylate histones and non-histone proteins including transcription factors thereby regulating metabolism, stress resistance, cellular survival, cellular senescence/aging. The aim of our study was to evaluate SIRT-1 expression in patients with lung squamous cell carcinoma and adenocarcinoma and these co-morbid with COPD. Methods: 93 patients with lung nonsmall cell lung carcinoma co-morbid with moderate severity COPD (n=29) or without COPD were enrolled in the study. Lung function testing was performed within one week before lung surgery. SIRT-1 e…

A progressive stage IIIB melanoma treated with oncolytic ECHO-7 virus: A case report

Melanoma is an aggressive skin cancer form with a grave prognosis. Current results suggest that oncolytic virus treatment of melanoma has a high therapeutic potential. ECHO-7 (Rigvir) is the first oncolytic virus registered in Latvia. A female patient was diagnosed with stage IIIB melanoma in December 2012, over 9.4 years ago. After the first excision and re-excision, the patient had several recurrences and disease progressions. After the patient had received surgical treatment in 2014, ECHO-7 virus oncolytic virotherapy was started. Since then, the patient has experienced only one more disease progression episode in May 2015 and has been stable for over 60 months. The patient has not rece…

Hroniskas obstruktīvas plaušu slimības (HOPS) molekulārie mehānismi centrālajos un perifērajos elpceļos

Hroniskai obstruktīvai plaušu slimībai (HOPS) ir raksturīga progresējoša un neatgriezeniska plaušu funkciju pasliktināšanās, ko izraisa hroniska elpceļu obstrukcija. Elpceļu obstrukciju novērtē, izmantojot spirometriju. HOPS pašlaik ir ceturtais no biežākajiem mirstības iemesliem Eiropā un ASV, taču tiek prognozēts, ka, smēķētāju skaitam pieaugot, 2020. gadā šī slimība būs jau trešais biežākais nāves cēlonis. Šī darba mērķis bija novērtēt, vai pastāv atšķirības starp iekaisuma procesa mehānismiem centrālajos un perifērajos elpceļos nesmēķētājiem, asimptomātiskiem smēķētājiem un vidēji smagas pakāpes HOPS pacientiem. Darba uzdevumi. Primārais: kvantitatīvi novērtēt iekaisuma šūnu infiltrācij…

Management of a primary malignant melanoma of uterine cervix stage IVA patient with radical surgery and adjuvant oncolytic virus Rigvir® therapy: A case report

Abstract Primary malignant melanoma of the uterine cervix is a rare disease with poor prognosis and high recurrence rate. We used Rigvir® as adjuvant therapy for a stage IVA patient. Tolerability, overall and progression‐free survival are good.

Neuroprotective properties of mildronate, a mitochondria-targeted small molecule.

Mildronate, a representative of the aza-butyrobetaine class of drugs with proven cardioprotective efficacy, was recently found to prevent dysfunction of complex I in rat liver mitochondria. The present study demonstrates that mildronate also acts as a neuroprotective agent. In a mouse model of azidothymidine (anti-HIV drug) neurotoxicity, mildronate reduced the azidothymidine-induced alterations in mouse brain tissue: it normalized the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and iNOS expression assessed by quantitative and semi-quantitative analysis. Mildronate also normalized the changes in cytochrome c oxidase (COX) expression, reduced the expression of glia…

Germinal Centers Determine the Prognostic Relevance of Tertiary Lymphoid Structures and Are Impaired by Corticosteroids in Lung Squamous Cell Carcinoma.

Abstract In solid tumors, the presence of lymph node–like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS develop in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multispectral microscopy, quantitative pathology, and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction. We identified a niche of CXCL13+ perivascular and CXCL12+LTB+ and PD-L1+ epithelial cells supporting TLS formation. We also characterized sequential stages of TLS maturation…

Severe Clostridium difficile infection with extremely high leucocytosis complicated by a concomitant bloodstream infection caused by Klebsiella pneumoniae after osteomyelitis surgery: A case report

Highlights • Exposure to antibiotics after surgery increase risk of Cl. difficile infection. • Sudden high leucocytosis may be sign of poor outcome in Cl. difficile case. • Oral Vancomycin could be responsible for the growth of bloodstream Kl. pneumonia.

Poly-ADP ribose polymerase, xanthine oxidase and nitric oxide synthase expression in kidney tissue of experimental diabetes

Background The spatial distribution of inflammatory and DNA reparation markers in the kidney tissue in diabetes is poorly understood. Aim The present study investigated the role of endothelial and inducible nitric oxide synthase (eNOS and iNOS), Poly ADP ribose polymerase (PARP) xanthine oxidase (XO) in the pathogenesis of streptozotocin-induced diabetic changes in the kidney tissue. Methods Diabetes mellitus was induced in rats by a single injection of streptozotocin (STZ) at a dose of 50 mg/kg. The XO, PARP, eNOS and iNOS protein expression in the kidney was studied by immunohistochemistry. Results Obtained results showed that STZ administration incresed the numbers of PARP and XO-positiv…

Associations of epstein-barr virus-positive gastric adenocarcinoma with circulating mediators of inflammation and immune response

Epstein-Barr virus (EBV)-positive gastric adenocarcinoma exhibits locally intense inflammation but systemic manifestations are uncertain. Our study examined whether circulating mediators of inflammation and immune response differ by tumor EBV status. From a Latvian series of 302 gastric cancer cases, we measured plasma levels of 92 immune-related proteins in the 28 patients with EBV-positive tumors and 34 patients with EBV-negative tumors. Eight markers were statistically significantly higher with tumor EBV positivity: chemokine C-C motif ligand (CCL) 20 (Odds Ratio (OR) = 3.6; p-trend = 0.001), chemokine C-X-C motif ligand 9 (OR = 3.6; p-trend = 0.003), programmed death-ligand 1 (PD-L1; OR…

Oxidative stress and innate immunity status in chickens exposed to high dose of ascorbic acid

The effects of high dose ascorbic acid (10 000 mg·kg–1 in the diet) and the transition metal on the presence of oxidative stress in the internal organs of growing chicks, as well as on the innate immune system status, were investigated. Supplementation with a high dose of ascorbic acid had pro-inflammatory effects on the intestinal mucosa, and lysozyme levels were decreased significantly in all organs studied. High-dose ascorbic acid caused an imbalance between prooxidative and antioxidative activities and was associated with the generation of semiquinone radicals. We observed that ascorbic acid increased iron and cadmium absorption. When a high dose of ascorbic acid was applied, elevated k…

Modifications of expression of genes and proteins involved in DNA repair and nitric oxide metabolism by carbatonides [disodium-2,6-dimethyl-1,4-dihydropyridine- 3,5-bis(carbonyloxyacetate) derivatives] in intact and diabetic rats

Abstract Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective. UV/VIS spectroscopy revealed that styrylcarbatone manifested a hyperchromic effect when interacting with DNA, while all other carbatonides showeda hypochromic effec…

Long‐term treatment with the oncolytic ECHO‐7 virus Rigvir of a melanoma stage IV M1c patient, a small cell lung cancer stage IIIA patient, and a histiocytic sarcoma stage IV patient‐three case reports

Oncolytic virotherapy is a recent addition to cancer treatment. Here, we describe positive treatment outcomes in three patients using Rigvir virotherapy. One of the patients is diagnosed with melanoma stage IV M1c, one with small cell lung cancer stage IIIA, and one with histiocytic sarcoma stage IV. The diagnoses of all patients are verified by histology or cytology. All patients started Rigvir treatment within a few months after being diagnosed and are currently continuing Rigvir treatment. The degree of regression of the disease has been determined by computed tomography. Safety assessment of adverse events graded according to NCI CTCAE did not show any value above grade 1 during Rigvir(…

Prostate Specific Antigen Dynamics and Features in Prostate Cancer

Abstract Despite the common use of the prostate-specific antigen (PSA) serum level as a tumour marker in diagnosis of prostate cancer, it seems that the PSA doubling time (PSADT) and PSA velocity (PSAV) could be more useful indicators of tumour behaviour and prognosis for patients. The aim of the study was to evaluate the value of PSAV and PSADT in the diagnosis of prostate cancer and their relationship with prostate cancer histopathological characteristics. Eighty-six patients undergoing radical prostatectomy were enrolled in the study. Based on the PSA measurements the PSA dynamic values were calculated: PSADT and PSAV. In addition, clinical and histo-pathological characteristics, includi…

Mildronate as a Regulator of Protein Expression in a Rat Model of Parkinson’s Disease

Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson’s disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell …

P33 Up-regulation of FOXP3 T regulatory lymphocytes in patients with high-grade squamous intraepithelial lesions correlated with HPV infection

Introduction/Background Regulatory (FOXP3+) T cells (Tregs) comprise a subpopulation of CD4+ T cells that suppress autoreactive immune cells, thereby protecting organs and tissues from autoimmunity. Novel therapeutic strategies for cervical cancer and squamous intraepithelial lesions (SIL) focus on immune-modulatory and cancer vaccination approaches. The aim of this study was to analyze the role of T regulatory cells (Tregs), CD4 and CD8 T lymphocytes and HPV status in low and high grade squamous intraepithelial lesions (LSIL and HSIL). Methodology 62 patients were enrolled in the study in Riga East University Hospital. Each patient had undergone a biopsy or electroexcision of the cervix. T…

Changes in glucose transporter expression and nitric oxide production are associated with liver injury in diabetes

In diabetes mellitus (DM), both hyperglycaemia and hyperlipidaemia can initiate accumulation of fat in the liver, which might be further mediated by inducible nitric oxide synthase. We have studied changes in GLUT1, nitric oxide (NO(·)) concentration and liver damage in two rat DM models. STZ model was induced by strepozotocin 50 mg/kg. HS model was induced by high-fat diet and 30 mg/kg streptozotocin. GLUT1 expression was studied by means of real-time RT-PCR and immunohistochemistry. Production of NO(·) was monitored by means of erythrocyte sedimentation rate spectroscopy of Fe-DETC-NO complex. Liver damage was assessed using histological activity index (HAI). NO(·) concentration was incre…

Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease

Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6‑OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); …

Abstract 2370: Elevated levels of anti-Epstein Barr virus (EBV) antibodies in EBV-associated gastric carcinoma

Abstract Background: Almost 10% of gastric carcinomas contain Epstein-Barr virus (EBV) DNA, which is not found in other gastrointestinal tract cancers. EBV-positive tumors have distinct clinico-epidemiologic features and are molecularly characterized by recurrent PIK3CA and absent TP53 mutations, JAK2 and PD-L1/L2 amplifications, and extreme DNA hypermethylation. Identification of the gastric cancer-specific antibody response to this common infection may elucidate its contribution to carcinogenesis and provide a non-invasive method to detect EBV-positive gastric tumors. Methods: Plasma samples from Latvian patients with EBV-positive (n=28) and -negative (n=34) gastric cancer were immune-pro…

Addressing the importance of melanoma tumor‑infiltrating lymphocytes in disease progression and clinicopathological characteristics

Tumor-infiltrating lymphocytes (TILs) in primary cutaneous melanoma are considered to represent the host's antitumor immunological response; however, whether there are associations between TIL grade and histopathological characteristics and disease survival remains controversial. BRAF mutational status has been established as a routine screening method in advanced malignant melanoma, and worse prognosis rates have been demonstrated in patients harboring BRAF mutations. However, the general impact of BRAF mutational status on survival and histopathological characteristics is still debated. The aim of the present study was to compare the value of the assessment of TIL grade in stages I-II nod…

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study The aim of our study was to compare the influence of pre-treatment with H1-antihistamines (levocetirizine, desloratadine, clemastine, quifenadine, and sequifenadine) and a placebo on the histamine-induced weal and flare reaction, increase of skin blood perfusion and sedation. Thirty healthy volunteers were enrolled in the study. The study design was a prospective, randomised, double-blind, placebo-controlled, crossover, balanced clinical trial. Volunteers in randomised and double-blind order were treated with …

Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) e…

Effects of Lycopene, Indole-3-Carbinol, and Luteolin on Nitric Oxide Production and iNOS Expression are Organ-Specific in Rats

Effects of Lycopene, Indole-3-Carbinol, and Luteolin on Nitric Oxide Production and iNOS Expression are Organ-Specific in RatsNatural compounds are known to modify NO content in tissues; however, the biological activity of polyphenol-rich food often does not correspond to the effects of individual polyphenols on NO synthase activity. The aim of this study was to see how natural compounds luteolin, indole-3-carbinol, and lycopene modify NO production in rat tissues and change the expression of the iNOS gene and protein. Indole-3-carbinol produced multiple effects on the NO level; it significantly decreased NO concentration in blood, lungs, and skeletal muscles and increased it in the liver. …

Melanoma Unknown Primary Brain Metastasis Treatment with ECHO-7 Oncolytic Virus Rigvir: A Case Report

Melanoma is considered an aggressive malignancy with a tendency for forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of this disease. Melanoma brain metastases have many severe side effects and unfortunately, any disease related to the brain has limited therapeutic options due to the blood brain barrier. The course of the disease after completing a treatment course, and stopping the treatment, is complicated to predict and is difficult to obtain long-lasting remission. In this report we describe a female patient with un…

Expression of p63, p53 and ki-67 in patients with cervical intraepithelial neoplasia

Objective: Cervical intraepithelial neoplasia (CIN) is a dysplastic process in cervical squamous epithelium and carries a risk of progression to cervical cancer. The aim of this study was to compare expression of three biomarkers named p53, p63 and Ki-67 in patients with various grades of cervical intraepithelial neoplasia and in a control group. Material and Method: 58 patients were enrolled in the study. Each patient underwent a colposcopy-guided biopsy of the cervix. Immunostaining for markers (p53, p63 and Ki-67) was performed on tissue samples of normal cases (n=10), CIN I (n=20), CIN II (n=14), and CIN III (n=14). Results: Our study showed a significant increase of the expression of t…

Search for Stroke-Protecting Agents in Endothelin-1-Induced Ischemic Stroke Model in Rats

Background and Objective. Ischemic stroke may initiate a reperfusion injury leading to brain damage cascades where inflammatory mechanisms play a major role. Therefore, the necessity for the novel stroke-protecting agents whose the mechanism of action is focused on their anti-inflammatory potency is still on the agenda for drug designers. Our previous studies demonstrated that cerebrocrast (a 1,4-dihydropyridine derivative) and mildronate (a representative of the aza-butyrobetaine class) possessed considerable anti-inflammatory and neuroprotective properties in different in vitro and in vivo model systems. The present study investigated their stroke-protecting ability in an endothelin-1 (ET…

Pepsinogen Test for the Evaluation of Precancerous Changes in Gastric Mucosa: a Population-Based Study

Aims: The aim of the study was to evaluate the rationale of blood pepsinogen (PG) testing in population based screening settings.Methods: Participants from a cross-sectional population-based study of cardiovascular risk factors in Latvia were invited to participate in the current study. Pepsinogen I and II were measured in blood samples taken during the initial study and at follow-up; upper gastrointestinal endoscopy was performed. There were three groups of patients: with moderately decreased (PG I< 70 ng/ml and PG I/PG II ratio < 3), with strongly decreased (PG I< 30 ng/ml and PG I/PG II ratio < 2), and with normal PG level. Biopsy with H. pylori detection was performed (updat…

Effects of Indole-3-Carbinol and Flavonoids Administered Separately and in Combination on Nitric Oxide Production and iNOS Expression in Rats

Beneficial effects of natural compounds are often attributed to modulation of NO production; however effects produced by plant extracts do not correlate with effects of purified components. The goal of our work was to study ability of flavonoids and indole-3-carbinol, as well as their combinations to modify NO production, iNOS gene and protein expression in rat tissues. Baicalein and luteolin decreased NO concentration in both intact and LPS-treated animals. Baicalein decreased iNOS gene expression. Luteolin decreased NO production in the liver and heart and number of iNOS-positive cells in the liver of LPS-treated animals. Combination of the two substances did not decrease the NO synthesis…

Clinicopathological characteristics of Epstein-Barr virus-positive gastric cancer in Latvia

Objective Epstein-Barr virus (EBV)-associated gastric cancer has been proposed to be a distinct gastric cancer molecular subtype. The prognostic significance of EBV infection in gastric cancer remains unclear and needs further investigation. Our study aimed to analyze EBV-positive and EBV-negative gastric cancer patients regarding their personal and tumor-related characteristics, and compare their overall survival. Methods Gastric cancer patients consecutively treated at the Riga East University Hospital during 2009-2016 were identified retrospectively. Tumor EBV status was determined by in-situ hybridization for EBV-encoded RNA (EBER). Information about clinicopathological characteristics …

Increased innate and adaptive immune responses in induced sputum of young smokers

Background and objectives: It is known that chronic obstructive pulmonary disease (COPD) development process is imperceptible and can be asymptomatic for 20 or more years. It is of great importance to diagnose early inflammatory changes that can lead to COPD in young asymptomatic cigarette smokers. The aim of our study was to analyze the cell spectrum of induced sputum (IS) of young cigarette smokers, with emphasis on T-regulatory cells. Materials and methods: A total of 20 healthy nonallergic smokers, 20 nonsmokers and 20 COPD patients were enrolled in the study. After lung function measurements were taken, we performed sputum induction and analyzed sputum cells. We evaluated the cell coun…

Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays.

Background Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy. Methods We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays …

Correction of glycaemia and GLUT1 level by mildronate in rat streptozotocin diabetes mellitus model

Anti-ischaemic drug mildronate suppresses fatty acid metabolism and increases glucose utilization in myocardium. It was proposed that it could produce a favourable effect on metabolic parameters and glucose transport in diabetic animals. Rats with streptozotocin diabetes mellitus were treated with mildronate (100 mg/kg daily, per os, 6 weeks). Therapeutic effect of mildronate was monitored by measuring animal weight, concentrations of blood glucose, insulin, blood triglycerides, free fatty acids, blood ketone bodies and cholesterol, glycated haemoglobin per cent (HbA1c%) and glucose tolerance. GLUT1 mRNA and protein expression in kidneys, heart, liver and muscles were studied by means of re…

Prevalence of Atrophic Gastritis in Kazakhstan and the Accuracy of Pepsinogen Tests to Detect Gastric Mucosal Atrophy

Background Atrophic gastritis is considered precursor condition for gastric cancer. There is so far limited evidence on the performance of pepsinogens for atrophy detection in Central Asia. The aim of our study was to detect the prevalence of atrophic gastritis in the asymptomatic adult population in Kazakhstan as well as address the accuracy of pepsinogen testing in atrophy detection. Methods Healthy individuals aged 40-64 were included. Upper endoscopy and pepsinogens (PG) evaluation were performed. PG were analysed in plasma by latex agglutination. Cut off values were used to define decreased PG values (PGR ≤ 3 and PG I ≤ 70 ng/mL); severely decreased PG values (PGR ≤ 2 and PG I ≤ 30 ng/…

Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

<i>Background:</i> Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airway obstruction. Smoking causes persistent inflammation in lung tissue. However, differences in inflammatory responses between the large and small airways have not been systematically explored among smokers with and without COPD. <i>Objectives:</i> The aim of our research was to characterise the expression and localisation of NF-ĸBp65 and histone deacetylase 2 (HDAC2) as well as inflammatory cell (macrophages, lymphocytes, neutrophils) distribution in large and small airways, in nonsmokers and in smokers with and without COPD. <i>Methods:</i&gt…

Accuracy of two plasma antibody tests and faecal antigen test for non-invasive detection of H. pylori in middle-aged Caucasian general population sample

Objective: The aim of the study was to assess the accuracy of two plasma Helicobacter pylori (H. pylori) antibody test-systems and a stool antigen test (SAT) system in a general population sample in Latvia. Materials and methods: Blood and faecal samples were analysed in healthy individuals (40–64 years), referred for upper gastrointestinal endoscopy according to pilot study protocol within a population-based study investigating gastric cancer prevention strategies (GISTAR pilot study). Antibodies to H. pylori were assessed in plasma by latex-agglutination test and enzyme-linked immunosorbent assay (ELISA). H. pylori antigen in faecal samples was detected by a monoclonal enzyme immunoassay-…

Sensing gastric cancer via point‐of‐care sensor breath analyzer

Background Detection of disease by means of volatile organic compounds from breath samples using sensors is an attractive approach to fast, noninvasive and inexpensive diagnostics. However, these techniques are still limited to applications within the laboratory settings. Here, we report on the development and use of a fast, portable, and IoT-connected point-of-care device (so-called, SniffPhone) to detect and classify gastric cancer to potentially provide new qualitative solutions for cancer screening. Methods A validation study of patients with gastric cancer, patients with high-risk precancerous gastric lesions, and controls was conducted with 2 SniffPhone devices. Linear discriminant an…

Distinct influence of atypical 1,4-dihydropyridine compounds in azidothymidine-induced neuro- and cardiotoxicity in mice ex vivo.

This study demonstrates the effective protection by compounds of atypical 1,4-dihydropyridine (DHP) series cerebrocrast, glutapyrone and tauropyrone against neuro- and cardiotoxicity caused by the model compound azidothymidine, a well-known mitochondria-compromising anti-HIV drug. In previous in vitro experiments, we have demonstrated distinct effects of these DHP compounds to influence mitochondrial functioning. In the present in vivo experiments, DHP compounds were administered intraperitoneally in mice daily for 2 weeks, per se and in combinations with azidothymidine at doses: azidothymidine 50 mg/kg; cerebrocrast 0.1 mg/kg; glutapyrone 1 mg/kg; and tauropyrone 1 mg/kg. At the end of the…

The Prevalence of Cancer-Associated Autoantibodies in Patients with Gastric Cancer and Progressive Grades of Premalignant Lesions.

Abstract Background: Serum autoantibodies against tumor-associated antigens (TAAs) are detectable in early-stage gastric cancer patients; however, the time point during cancerogenesis when they appear in circulation is still obscure. Methods: In this study, we developed a recombinant antigen microarray and analyzed the prevalence of autoantibodies against 102 TAAs in 829 gastric cancer patients and 929 healthy controls from Caucasian and Asian populations, as well as 100 patients with chronic atrophic gastritis and 775 individuals staged according to different grades of intestinal metaplasia. Results: Six antigens, including CTAG1B/CTAG2, DDX53, IGF2BP2, TP53, and MAGEA3, were predominantly…

Cadmium-Induced Enteropathy in Domestic Cocks: A Biochemical and Histological Study after Subchronic Exposure

The biochemical and histological sequelae resulting from a diet containing 50.20 mg cadmium/kg were studied in Lohmann brown cockerels from hatching until 30 days of age. The additional cadmium chloride (CdCl(2)) to the diet induced the formation of lipid peroxides, which via a chain reaction led to accumulation of malondialdehyde in intestinal mucosa. At the end of the study (after 30 days of cadmium exposure) total protein and metallothionein levels in the intestinal mucosa and the relative ileal and duodenal weight increased. Histological data show that CdCl(2) causes an increase in number of goblet cells and granular lymphocytes in the intestinal mucosa. Down-regulation of the serotonin…

Decreased FOXP3 expression in small airways of smokers with COPD

CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients. A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large a…

CD63 and Dna Mismatch Repair Protein Expression in Prostate Cancer

Abstract Protein expression levels in immunohistochemistry and molecular biomarkers have been reported for their ability to predict recurrence, progression, development of metastases, and patient survival. The molecular features in low- and high-grade prostate cancer can differ and influence treatment decision and prognosis. The objective of the current study was to compare the expression of exosomal biomarkers CD63 and mismatch repair proteins (MSH2, MSH6, MLH1, and PMS2) by immunohistochemistry (IHC) in tissue of patients with prostate cancer and benign hyperplasia. Altogether, 62 patients with prostate acinar adenocarcinoma and 20 patients with prostate benign hyperplasia were enrolled i…

Different Pattern of Inflammatory and Atrophic Changes in the Gastric Mucosa of the Greater and Lesser Curvature.


 
 
 
 
 
 Background & Aims: Appropriate biopsy sampling is important for the classification of gastritis, yet the extent of inflammation and atrophy of different regions of the stomach with chronic gastritis have been addressed only in a few studies. The aim of our study was to analyze the inflammatory, atrophic and metaplastic changes in the greater and lesser curvature of the antrum and corpus mucosa.
 Methods: 420 patients undergoing upper endoscopy were enrolled in the study. Four expert gastrointestinal pathologists graded biopsy specimens according to the updated Sydney classification.
 Results: The obtained results showed that the mononu…

Different Patterns of Lung Sirtuin Expression in Smokers With and Without Chronic Obstructive Pulmonary Disease

Background and Objective. Chronic obstructive pulmonary disease is characterized by persistent and modified inflammatory responses in lung. Human sirtuin, an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. The aim of our study was to compare the expression of sirtuin in large and small airways in nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease. Material and Methods. A total of 12 nonsmokers, 14 asymptomatic smokers, and 12 smokers with moderate chronic obstructive pulmonary disease were enrolled into the study…

Comparison of the Effects of Glibenclamide on Metabolic Parameters, GLUT1 Expression, and Liver Injury in Rats With Severe and Mild Streptozotocin-Induced Diabetes Mellitus

Background and Objective. Glucose transport via GLUT1 protein could be one of additional mechanisms of the antidiabetic action of sulfonylureas. Here, the GLUT1 gene and the protein expression was studied in rats in the course of severe and mild streptozotocin-induced diabetes mellitus and under glibenclamide treatment. Material and Methods. Severe and mild diabetes mellitus was induced using different streptozotocin doses and standard or high fat chow. Rats were treated with glibenclamide (2 mg/kg daily, per os for 6 weeks). The therapeutic effect of glibenclamide was monitored by measuring several metabolic parameters. The GLUT1 mRNA and the protein expression in the kidneys, heart, and l…

Mildronate and its neuroregulatory mechanisms: targeting the mitochondria, neuroinflammation, and protein expression.

This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate…

Hroniskas obstruktīvas plaušu slimības molekulārie mehānismi centrālajos un perifērajos elpceļos

ANOTĀCIJA Ievads. Hroniskai obstruktīvai plaušu slimībai (HOPS) ir raksturīga progresējoša un neatgriezeniska plaušu funkciju pasliktināšanās, ko izraisa hroniska elpceĜu obstrukcija. ElpceĜu obstrukciju novērtē, izmantojot spirometriju. HOPS pašlaik ir ceturtais no biežākajiem mirstības iemesliem Eiropā un ASV, taču tiek prognozēts, ka, smēėētāju skaitam pieaugot, 2020. gadā šī slimība būs jau trešais biežākais nāves cēlonis. Šī darba mērėis bija novērtēt, vai pastāv atšėirības starp iekaisuma procesa mehānismiem centrālajos un perifērajos elpceĜos nesmēėētājiem, asimptomātiskiem smēėētājiem un vidēji smagas pakāpes HOPS pacientiem. Darba uzdevumi. Primārais: kvantitatīvi novērtēt iekaisum…

Current Trends in Prostate Cancer Etiology, Pathogenesis and Diagnostics

Abstract Prostate cancer (PCa) remains the second most commonly diagnosed cancer in men, with an estimated 1.1 million diagnoses worldwide in 2012, accounting for 15% of all cancers diagnosed. In many cases, successful treatment of prostate cancer is difficult due to late detection and rate of metastasis. Importantly, the tumours of many patients with prostate cancer become refractory to androgen therapy and progress to metastatic castration-resistant disease. An effective treatment course of prostate cancer patients requires predictive biomarkers in metastatic castration-resistant prostate cancer that support individual treatment. Different risk classification tools have been developed to …