Evaluation of Blood Coagulation Parameters and ADMA, NO, IL-6, and IL-18 Serum Levels in Patients with Neovascular AMD before, during, and after the Initial Loading Phase of Intravitreal Aflibercept.

We evaluated the effect of intravitreal injections of aflibercept (IVA) on blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), as well as asymmetric dimethylarginine (ADMA), nitric oxide (NO), interleukin 6 (IL-6), and interleukin 18 (IL-18) serum levels in patients with neovascular AMD (nAMD). Twenty-two eyes of 22 patients with nAMD were included. Parameters were evaluated before and 2-3 days after the first IVA injection, and then immediately before and 2-3 days after the third IVA injection. We revealed prolongation of the TT after the initial loading phase of IVA (p = 0.041) and a significant increase in IL-18 serum concentration immediately before the third IVA administration compared to baseline (p = 0.037). There were no statistically significant differences of other parameters and PT, APTT, ADMA, NO, and IL-6 values remained within the normal range at each of the time points of the study. Our results suggest that repeated IVA administration may affect the common blood coagulation pathway, which manifests as a prolongation of the TT value. Furthermore, we showed a significant increase in serum concentration of the pro-inflammatory cytokineIL-18during the initial loading phase of IVA.

The Impact of Modern Therapeutic Methods on the Oxidant-Antioxidant Equilibrium and Activities of Selected Lysosomal Enzymes and Serine Protease Inhibitor in Amateur Athletes.

Deep electromagnetic stimulation (DEMS) and low-frequency ultrasound (US) are new physical therapy methods used in the rehabilitation of the musculoskeletal system and wound healing. They are applied locally to treat the injured tissues. The beneficial effects of these methods in supportive care have been documented, but accurate biochemical effects are not known. The goal was to assess the effect of single DEMS and US sessions on the oxidant-antioxidant equilibrium, as well as the activities of lysosomal hydrolases and α 1-antitrypsin (AAT) in peripheral blood of juvenile injured amateur athletes. In the athletes with low back pain (DEMS treated, N = 16) and pain in the shoulder or ankle joint (US treated, N = 14), as well as in healthy control amateur athletes (DEMS treated, N = 14; US treated, N = 17), before the sessions and 30 minutes and 24 hours after them, the levels of the following parameters were determined: thiobarbituric acid reactive substances (TBARS) in erythrocytes and plasma, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in erythrocytes, as well as acid phosphatase (AcP), arylsulfatase (ASA), cathepsin D (CTS D), and α 1-antitrypsin (AAT) in serum. After both procedures, the levels of parameters changed in a negligible manner, excluding the cathepsin D activity, which was statistically significantly lower 30 min and 24 h after US in the control athletes compared to the baseline activity determined directly before the procedure (47.5% and 55.7% differences, respectively). Similar tendency was observed after DEMS (p > 0.05). The procedures, especially low-frequency US, decrease lysosomal proteolytic activity and do not significantly disrupt the oxidant-antioxidant and lysosomal equilibriums in the peripheral blood both of healthy and injured athletes. No systemic acute-phase response of AAT was also detected in the athletes after both procedures. This trial is registered with CTRI/2018/01/011344.

Resveratrol's Impact on Vascular Smooth Muscle Cells Hyporeactivity: The Role of Rho-Kinase Inhibition.

Resveratrol (3,5,4'-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. The aim of the present study was to determine the influence of resveratrol application along with certain modulating factors, such as 8Br-cGMP-activator of cGMP-dependent protein kinases, HA-1077-Rho-kinase inhibitor, and Bay K8644-calcium channel agonist, on VMSCs constriction triggered by phenylephrine. Resveratrol at a dose of 10 mg/kg/24 h administered for 4 weeks reduced the reactivity of the arteries to the pressure action of catecholamines. Tests performed after four weeks of resveratrol administration showed that 8Br-cGMP at the concentrations of 0.01 mM/l and 0.1 mM/l intensifies this effect. Simultaneous resveratrol and Bay K8644 administration led to a significant decrease in contractility compared to the vessels collected from animals (Res-). This effect was dependent on the concentration of Bay K8644. Resveratrol seems to be counteractive against Bay K8644 by blocking L-type calcium channels. As the concentration of HA-1077 increased, there was a marked hyporeactivity of the vessels to the pressure effects of phenylephrine. The results indicate synergy between resveratrol and Rho-kinase inhibition.

Post-Lumbar Puncture Headache-Does Hydration before Puncture Prevent Headache and Affect Cerebral Blood Flow?

Headache is a common complication after diagnostic lumbar puncture (DLP). We aimed to check whether hydration before puncture influences the incidence of post-lumbar puncture headache (PLPH) and affects cerebral blood flow. Ninety-nine patients enrolled for puncture were assigned to a group with (n = 40) or without hydration (n = 59). In the hydration group, 1000 mL 0.9% NaCl was infused and a minimum of 1500 mL oral fluids was recommended within the 24 h before puncture. A Transcranial Doppler (TCD) was performed before and after DLP. Mean velocity (Vm) and pulsatility index (PI) were measured in the middle cerebral arteries (MCAs). PLPH occurred in 28 patients (28.2%): six (15.4%) from the hydrated and 22 (37.3%) from the non-hydrated group (p < 0.023). Patients with PLPH were younger (p < 0.014) and with headaches in their histories (p < 0.036) compared with the non-headache group. Vm values in both MCAs after puncture were significantly lower than before puncture in all patients. In the PLPH group, Vm in MCAs before puncture were significantly higher and the PI was lower than in the non-headache group. Our findings suggest that hydration of patients within 24 h before puncture prevented PLPH. Twenty-four hours after puncture, significant decreases in Vm were observed in the MCAs of all patients. Low baseline values of PI and high Vm predisposed patients to PLPH.

Neuroprotective Properties of Linagliptin: Focus on Biochemical Mechanisms in Cerebral Ischemia, Vascular Dysfunction and Certain Neurodegenerative Diseases.

Linagliptin is a representative of dipeptidyl peptidase 4 (DPP-4) inhibitors which are registered and used effectively in a treatment of diabetes mellitus type 2. They increase the levels of active forms of endogenous incretins such as GLP-1 and GIP by inhibiting their enzymatic decomposition. Scientific reports suggest beneficial effects of linagliptin administration via immunological and biochemical pathways involved in neuroprotective processes of CNS. Linagliptin's administration leads to a decrease in the concentration of proinflammatory factors such as: TNF-α, IL-6 and increases the number of anti-inflammatory patrolling monocytes CX3CR1bright. Significant reduction in Aß42 level has been associated with the use of linagliptin implying potential application in Alzheimer's disease. Linagliptin improved vascular functions by increasing production of nitric oxide (NO) and limiting concentration of apolipoprotein B. Linagliptin-induced decrease in macrophages infiltration may provide improvement in atheromatous plaque stabilization. Premedication with linagliptin increases neuron's survival after stroke and augments neuronal stem cells proliferation. It seems to be connected with SDF-1α/CXCR4 signaling pathway. Linagliptin prevented abnormal proliferation and migration of rat brain microvascular endothelial cells in a state of hypoperfusion via SIRT1/HIF-1α/VEGF pathway. The article presents a summary of the studies assessing neuroprotective properties of linagliptin with special emphasis on cerebral ischemia, vascular dysfunction and neurodegenerative diseases.

Effect of hyperglycemia on cerebral blood flow in patients with diabetes.

AIMS: Diabetes interferes with cerebral blood flow (CBF) and it seems that the effect of acute hyperglycemia on CBF is different from the changes in CBF caused by chronic diabetes. The aim of the study was to check whether there are changes in CBF measured using transcranial Doppler (TCD) in patients with hyperglycemia before and after normalization of glycemia. METHODS: The study involved 29 patients with diabetes and 27 healthy subjects (control group). The TCD test evaluated mean flow velocity (Vm), systolic velocity (Vs) and Gosling's pulsatility index (PI) in both middle cerebral arteries (MCAs). It was performed twice in patients with diabetes (during hyperglycemia and after normalization of glycemia) and once in the control group. RESULTS: The baseline blood flow parameters were similar in both groups. After the normalization of glycemia in patients with diabetes, they showed lower values of Vm and Vs compared to the control group (p < 0.001). Also, the normalization of glycemia caused a decrease in Vm and Vs (p < 0.001) in patients with diabetes. There were no significant differences in PI. CONCLUSIONS: In the patients with hyperglycemia, Vm and Vs in the MCA were higher than during normoglycemia, which was probably related to vasoconstriction and hypervolemia.

Quantitative anatomy of the primary ossification center of the radial shaft in human fetuses.

PURPOSE: The medical literature still lacks studies on the size of the radial shaft primary ossification center, thus preventing us from potentially relevant data in diagnosing skeletal dysplasias, i.e., TAR syndrome, VATER syndrome, Holt-Oram syndrome, Fanconi anemia and Edwards syndrome, frequently characterized by disrupted or retarded fetal growth. MATERIALS AND METHODS: The size of the radial shaft primary ossification center in 47 (25 males and 22 females) spontaneously aborted human fetuses aged 17-30 weeks was studied by means of CT, digital image analysis and statistics. RESULTS: With neither sex nor laterality differences, the best-fit growth dynamics for the radial shaft primary ossification center was modeled by the following functions: y = - 10.988 + 1.565 × age ± 0.018 for its length, y = - 2.969 + 0.266 × age ± 0.01 for its proximal transverse diameter, y = - 0.702 + 0.109 × age ± 0.018 for its middle transverse diameter, y = - 2.358 + 0.203 × age ± 0.018 for its distal transverse diameter, y = -189.992 + 11.788 × (age)2 ± 0.018 for its projection surface area, and y = - 798.174 + 51.152 × age ± 0.018 for its volume. CONCLUSIONS: The morphometric characteristics of the radial shaft primary ossification center show neither sex nor bilateral differences. The radial shaft primary ossification center grows proportionately in length, transverse dimensions and volume, and quadratically in its projection surface area. The obtained numerical findings of the radial shaft ossification center are considered age-specific reference of relevance in both the estimation of fetal ages and the diagnostic process of congenital defects.

A rare case of isolated pancreatic tuberculosis in a 70-year-old patient - a case report.

We report a case of rare solitary pancreatic tuberculoma. 70 years old woman admitted to hospital in order to conduct diagnostics of a tumor located in the head of the pancreas. All symptoms pointed at pancreatic cancer, but histopathological examinations were inconclusive. Additionally, there were no clinical signs or symptoms of tuberculosis in the lungs. X-ray of the chest showed no abnormalities. The patient denied tuberculosis in the medical interview. There were no bacilli in the sputum. During exploratory laparotomy, the samples of tissue have been taken for pathomorphological examination. The microscopic image caused suspicion of Mycobacterium tuberculosis etiology, which was confirmed by Ziehl-Neelsen staining. In recent years, tuberculosis has become more and more common in Europe, which is why the described case can be a guide for doctors to help to avoid diagnostic errors and speed up the treatment process.

Intermittent Fasting in Cardiovascular Disorders-An Overview.

Intermittent fasting is a form of time restricted eating (typically 16 h fasting and 8 h eating), which has gained popularity in recent years and shows promise as a possible new paradigm in the approach to weight loss and the reduction of inflammation, and has many potential long term health benefits. In this review, the authors will incorporate many aspects of fasting, mainly focusing on its effects on the cardiovascular system, involving atherosclerosis progression, benefits for diabetes mellitus type 2, lowering of blood pressure, and exploring other cardiovascular risk factors (such as lipid profile and inflammation).

Grey matter activation by caloric stimulation in patients with unilateral peripheral vestibular hypofunction.

PURPOSE: A combination of the caloric test with functional magnetic resonance imaging (fMRI) is a promising method for a comprehensive diagnostics of pathologies of the vestibular system. The aim of this study was to investigate the potential pattern of grey matter local activation in fMRI using cold and hot caloric stimulation in patients presenting unilateral peripheral vestibular injury. METHODS: Forty right-handed participants aged 27 to 56 with the diagnosis of right-sided peripheral vestibular hypofunction were included. Stimulation was performed separately for the right and the left ear with cold (C, 14-15 °C) stimulus and hot (H, 48-49 °C) stimulus. Grey matter activation was assessed in BOLD technique using a 3T scanner. RESULTS: We observed activity within the parieto-insular vestibular cortex (PIVC), thalamus, insula and retroinsular area, hippocampus, and cerebellum, as well as oculomotor centers located in the precentral gyrus, superior temporal gyrus, and intraparietal sulcus. Cold stimulus resulted in more areas of activation in response to the right ear activation rather than to the left ear. The ipsilateral activity was noted for insular cortex and intraparietal sulcus. The differences between hot and cold stimuli were noted for the right ear. CONCLUSIONS: In this preliminary study, the combination of the caloric test and fMRI allowed to present specific pattern of grey matter activation in patients with unilateral peripheral vestibular injury. Further studies are necessary to develop patterns or cortical maps differentiating various balance disorders and to analyze the dynamics of cortical plasticity after the injury.