A wise person plants a tree a day before the end of the world: coping with the emotional experience of climate change in Poland.

It is now widely accepted that we are in a climate emergency, and the number of people who are concerned about this problem is growing. Yet, qualitative, in-depth studies to investigate the emotional response to climate change were conducted either in high-income, western countries, or in low-income countries particularly vulnerable to climate change. To our knowledge, there are no qualitative studies conducted in countries that share great barriers to decarbonization while being significant contributors to carbon emissions. Since climate change affects people globally, it is crucial to study this topic in a variety of socio-political contexts. In this work, we discuss views and reflections voiced by highly concerned residents of Poland, a Central European country that is a major contributor to Europe's carbon emissions. We conducted 40 semi-structured interviews with Polish residents, who self-identified as concerned about climate change. A variety of emotions related to climate change were identified and placed in the context of four major themes: dangers posed by climate change, the inevitability of its consequences, attributions of responsibility, and commonality of concern. Our findings highlight a variety of often ambivalent and conflicting emotions that change along with the participant's thoughts, experiences and behaviours. Furthermore, we describe a wide repertoire of coping strategies, which promoted well-being and sustained long-term engagement in climate action. As such, our work contributes to research on a broad array of climate-related emotions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03807-3.

Clinical Significance of Gastrointestinal Carriage of Klebsiella Pneumoniae-Producing Extended-Spectrum Beta-Lactamases in Kidney Graft Recipients.

The burden of Klebsiella pneumoniae (KP) producing extended-spectrum beta-lactamases (ESBL+) urinary tract infections (UTIs) is a growing problem after kidney transplantation (KTX). The study was aimed at evaluating the incidence of KP ESBL+ gut colonization in KTX recipients and its correlation with clinical outcomes with special regard to UTIs. The study included all KTX patients hospitalized in our department between January 2014 and December 2016. During this period 2018 KTX patients were admitted: 605 in 2014, 750 in 2015, and 663 in 2016, respectively. Screening for drug-multiresistant Enterobacteriaceae gut carriage was performed in 104 patients (2014), 122 (2015), and 166 (2016). In 2014, 2015, and 2016, 18 (17.3%), 26 (21.3%), and 30 (18.1%) patients had positive test results, and 44 (42.3%), 36 (29.5%), and 45 (27.4%) KTX patients were diagnosed with KP ESBL+ UTI. In 2014, KP ESBL+ UTI was diagnosed in 30 (34.9%) cases with negative anal swab and in 14 patients (77.8%) with positive test result (P = .0008). In 2015, KP ESBL+ UTI was diagnosed in 21 patients (21.9%) with negative anal swab and in 15 (57.7%) with positive test result (P = .0004). In 2016, KP ESBL+ UTI was diagnosed in 24 patients (17.8%) with negative anal swab and in 21 (72.4%) with positive test result (P = .000001). In conclusion, we have revealed a strong association between gut K. pneumoniae colonization, female sex, and MPA intake and KP ESBL+ urinary tract infections in kidney transplant recipients. Our results indicate the very important role of KP ESBL+ screening, while strategies of identified carriers require further research.

Systolic myocardial volume gain in dilated, hypertrophied and normal heart. CMR study.

AIM: To investigate changes in myocardial tissue volume during the cardiac cycle to verify the hypothesis of non-compressibility of the myocardium in healthy individuals (HI) as well as in patients with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and aortic stenosis (AS). MATERIALS AND METHODS: The study group included 30 HI, and patients with HCM (n=110), DCM (n=89), and AS (n=78). Left ventricular (LV) function, end-diastolic, and end-systolic volumes were calculated based on cardiac magnetic resonance imaging (CMR) for all participants. RESULTS: End-systolic myocardial volumes were higher than end-diastolic in both controls (91.2±26.6 versus 85.1±24.3 ml, p<0.001) and in all patient groups: HCM (214.3±81.6 versus 176±64.2 ml, p<0.01), DCM (128.4±43.1 versus 115.4±42.9 ml, p<0.001) and AS (155.1±37.1 versus 129.4±34.6 ml, p<0.001). HCM and AS patients had significantly higher systolic volume gain than HI (21.5±8.3 versus 10.6±6.3%, p<0.01 and 18.3±5.7 versus 10.6±6.3% p=0.013, respectively). Conversely, DCM patients had lesser increases in myocardial systolic volume than HCM patients (11.2±4.8% versus 21.5±8.3, p=0.01) and AS patients (11.2±4.8% versus 18.3±5.7, p=0.02). No differences were found in systolic volume gain between AS and HCM patients (p=ns) or between DCM patients and HI (p=ns). CONCLUSION: End-systolic myocardial volume was significantly higher than end-diastolic volume in all subsets of patients. The systolic volume gain was greater in individuals with hypertrophy than in those without.

High frequency ultrasonography: a complementary diagnostic method in evaluation of primary cutaneous melanoma.

AIM: The aim of our study was to assess the usefulness of high frequency ultrasonography in the diagnosis of melanoma. METHODS: We examined 84 patients with suspicious melanocytic skin lesions, including 19 cases of melanoma. In vivo high-resolution ultrasonography (30 MHz) was performed prior to excision. RESULTS: In ultrasound scans early melanomas presented as flat oval or fusiform shaped structures and were clearly demarcated, while advanced melanomas were characterized by a roundish shape with less distinct borders. The ultrasonographic thickness of in situ melanomas ranged from 0.02 to 0.85 mm. In the case of invasive tumors, the mean thickness evaluated by high frequency ultrasonography was 10.7% higher compared to the Breslow Score (1.44±0.8 mm and 1.3±0.88 mm, respectively). In all melanomas of Breslow Score of 1 mm or more ultrasound also indicated a Breslow Score of 1 mm or more. CONCLUSION: High frequency ultrasound examination has limited value in differential diagnosis of melanoma, but it gives a clear picture of the size and depth of the tumor. The method should be used as a complementary method (after dermoscopy and, where applicable, reflectance confocal microscopy) in preoperative evaluation of the tumor. In some cases of locally advanced melanoma, ultrasound examination may allow to reduce the number of surgical procedures and favor the decision of a one-time surgical treatment (removal of primary tumor and sentinel lymph node biopsy at the same time).

Prevalence of ankylosing spondylitis in Poland and costs generated by AS patients in the public healthcare system.

The aim of the research was to analyse the prevalence of ankylosing spondylitis (AS) in Poland and to assess the costs generated by AS patients in the system of public health care. The database of national payer-National Health Fund (NHF)-has been analysed. For the analysis, the information has been extracted from IT system about each treated patient with ICD-10 = M45 code as main or coexisting diagnosis included in the mandatory reports from entities of public healthcare service. In the years 2008-2013, from 28,800 to 32,800 persons diagnosed with AS as main or coexisting diagnosis have been registered in NHF database. In 2013, the prevalence amounted to 7.48 for 10,000 persons of general population-the highest in Kujawy-Pomerania province (10.92 per 10,000 inhabitants), Silesia (10.04) and Swietokrzyskie province (9.81). In male patients, this coefficient amounted to 8.91 per 10,000 inhabitants, whereas in female-to 6.15. In 2013, the prevalence for men was the highest in the age group of 60-64 years and for women in the group of 65-69 years. The healthcare expenses related to AS financed by the NHF increased from 13,200 million PLN (6.3 million USD) in 2008 to 72,600 million PLN (21,900 million USD) in 2013. The increase in healthcare expenses related to AS patients in the public healthcare system is significant and noticeable. High regional diversity is also a vital issue. It is necessary to carry out further research on the incidence rate of AS in Polish population.

Relationship between Tetracyclines' Structure and Minimal Inhibitory Concentration of Streptococcus spp.

During the past years, a growing number of bacterial strains have become resistant to tetracyclines. The problem of increasing resistance and lack of susceptibility to tetracyclines applies to strains isolated from both: animals and humans. Basic tools to design new drugs and determining the direction of the search for new molecules is the analysis of the relationship between the chemical structure and the pharmacokinetic and pharmacodynamic parameters. Purpose of this study is to determine the relationship between physicochemical parameters of tetracyclines and MIC50 and MIC90 values determined for Streptococcus spp. Analysis of physicochemical parameters of selected drugs was made using MarvinSketch 5.11.5 (ChemAxon Ltd.) and QuickProp 3.1 software from Schrödinger package v 31207. MIC50 and MIC90 values were correlated with 51 calculated physicochemical parameters and arithmetic expressions. Internal and external model validation was performed using leave-one out method. 4 arithmetic expressions fulfilled all validation criteria, but only in relation to MIC50. A new method to optimize the tetracyclines' structure in relation to Streptococcus spp. was presented. It was also shown that the relations of structure: antimicrobial activity type can have different nature depending on MIC50 or MIC90 of specific bacterial strain.

Cardiothoracic ratio may be misleading in the assessment of right- and left-ventricular size in patients with repaired tetralogy of Fallot.

AIM: To assess the relationship between cardiothoracic ratio (CTR) and ventricular and atrial volumes in patients with repaired tetralogy of Fallot (TOF). MATERIALS AND METHODS: Patients with repaired TOF undergoing cardiac magnetic resonance (CMR) and chest radiography within 1 day were included (n = 82; median age: 24.7 years, interquartile range: 21.5-35.9). The CTR was obtained from upright posteroanterior chest roentgenograms. Analyses of CMR images and radiographs were performed in a blinded fashion. RESULTS: There were 35.1% (13/37) of patients with normal CTR (<0.5) who had severe right ventricular (RV) dilatation. There were six patients (13.3%, 6/45) with high CTR with both normal RV and left-ventricular (LV) volumes. CTR did not correlate with either RV or LV volumes but showed a weak correlation with right- and left-atrial volumes (r = 0.43, p = 0.0001; r = 0.27, p = 0.01, respectively). CTR ≥0.5 showed poor ability in the identification of severe RV dilatation (sensitivity: 61.8%, specificity: 50%). The combination of CTR and signs of RV enlargement on lateral radiographs did not improve the diagnostic accuracy of any of those parameters alone. CONCLUSION: CTR in patients with repaired TOF reflected atrial rather than ventricular dilatation. The use of CTR or lateral radiographs in patients with repaired TOF may lead to false conclusions concerning ventricular size.

Immunohistochemical properties of motoneurons supplying the trapezius muscle in the rat.

Combined retrograde tracing (using fluorescent tracer Fast blue) and double-labelling immunofluorescence were used to study the distribution and immunohistochemical characteristics of neurons projecting to the trapezius muscle in mature male rats (n = 9). As revealed by retrograde tracing, Fast blue-positive (FB+) neurons were located within the ambiguous nucleus and accessory nucleus of the grey matter of the spinal cord. Immunohistochemistry revealed that nearly all the neurons were cholinergic in nature [choline acetyltransferase (ChAT)-positive]. Retrogradely labelled neurons displayed also immunoreactivities to calcitonin gene-related peptide (CGRP; approximately 60% of FB+ neurons), nitric oxide synthase (NOS; 50%), substance P (SP; 35%), Leu5-Enkephalin (LEnk; 10%) and vasoactive intestinal polypeptide (VIP; 5%). The analysis of double-stained tissue sections revealed that all CGRP-, VIP- and LEnk-immunoreactive FB+ perikarya were simultaneously ChAT-positive. The vast majority of the neurons expressing SP- or NOS-immunoreactivity were also cholinergic in nature; however, solitary somata were ChAT-negative. FB+ perikarya were surrounded by numerous varicose nerve fibres (often forming basket-like structures) immunoreactive to LEnk or SP. They were also associated with some CGRP-, NOS- and neuropeptide Y-positive nerve terminals.

PssO, a unique extracellular protein important for exopolysaccharide synthesis in Rhizobium leguminosarum bv. trifolii.

Synthesis and secretion of polysaccharides by Gram-negative bacteria are a result of a concerted action of enzymatic and channel-forming proteins localized in different compartments of the cell. The presented work comprises functional characterization of PssO protein encoded within the previously identified, chromosomal exopolysaccharide (EPS) biosynthesis region (Pss-I) of symbiotic bacterium Rhizobium leguminosarum bv. trifolii TA1 (RtTA1). pssO gene localization between pssN and pssP genes encoding proteins engaged in exopolysaccharide synthesis and transport, suggested its role in EPS synthesis and/or secretion. RtTA1 pssO deletion mutant and the PssO protein overproducing strains were constructed. The mutant strain was EPS-deficient, however, this mutation was not complemented. The PssO-overproducing strain was characterized by increase in EPS secretion. Subcellular fractionation, pssO-phoA/lacZ translational fusion analyses and immunolocalisation of PssO on RtTA1 cell surface by electron microscopy demonstrated that PssO is secreted to the extracellular medium and remains attached to the cell. Western blotting analysis revealed the presence of immunologically related proteins within the species R. leguminosarum bv. trifolii, bv. viciae and Rhizobium etli. The secondary structure of PssO-His(6), as determined by FTIR spectroscopy, consists of at least 32% alpha-helical and 12% beta-sheet structures. A putative function of PssO in EPS synthesis and/or transport is discussed in the context of its cellular localization and the phenotypes of the deletion mutant and pssO-overexpressing strain.

The influence of acute progressive hypoxia on bioelectrical activity of the brain.

Hypoxia, a noxious and hyperventilatory stimulus and a modifier of neuronal metabolism, could influence cortical function. In this study we attempted to assess any such influence, its determinants, and particularly the role in it of the accompanying hypoxic emotional distress. We addressed the issue by examining the associations among EEG, ventilation, and anxiety during progressive poikilocapnic hypoxia (end-point SaO(2) approximately 75%) in 12 awake healthy volunteers (mean age 27.5 +/-0.7 yr). All subjects hyperventilated in response to hypoxia and 3 of them had a high level of anticipatory anxiety that forced one person to discontinue the test. We failed to show any major effect of hypoxia on the EEG pattern analyzed by visual inspection or wavelet power spectra. Therefore, no relationship between the ventilatory and cortical activity responses to hypoxia could be established. Cortical activity changes appeared, however, in the subjects who experienced emotional distress during the test. These changes were apparent on an expanded analysis of the EEG signal by the use of the Lempel-Ziv complexity that takes into account the ordering of variations in the signal, rather than only the relative frequency of events analyzed by the Shannon entropy. The Lempel-Ziv complexity offers promise as a novel method for unraveling fine and otherwise unexpressed alterations in cortical bioelectrical activity.

Neurotransmitter mechanisms in the enhancement of the hypoxic ventilatory response by antecedent hyperoxia in the anesthetized rat.

A brief period of antecedent oxygen breathing enhances the ventilatory response to hypoxia. The mechanisms of this phenomenon are uncertain and have been variably linked to the central glutamatergic or nitrergic pathways. In the present study we put a question of how blockade of either neurotransmitter pathway would compare with the concurrent blockade of them both in terms of the enhancement of posthyperoxic hypoxic ventilation. The study was performed on the anesthetized, vagotomized, spontaneously breathing rats divided into the following experimental groups: control NaCl-treated, glutamate blocker 2-amino-5-phosphonopentanoic acid (AP5)-treated, nitric oxide synthase blocker 7-nitroindazol (7NI)-treated, and AP5+7NI-treated. The protocol consisted of measuring the ventilatory response to 12% O2, a steady- state poikilocapnic hypoxia, undertaken in three consecutive conditions in each animal: the initial control, 25 min after injection of a given chemical agent, and then after a 15-min period of oxygen breathing. Respiration was evaluated from the diaphragmatic EMG signal. We found that the posthyperoxic hypoxic ventilatory enhancement was but partially dampened by either AP5 or 7NI. Concurrent administration of the two blockers further diminished, but did not abolish, the hypoxic ventilatory enhancement. We conclude that although the glutamate-NO system accounts for an appreciable part of the posthyperoxic hypoxic ventilatory enhancement, other, as yet unclear, mechanisms contribute as well. These mechanisms may be worth exploring given the substantial enhancing effect the antecedent oxygen has on hypoxic hyperventilation.

Stability of ascorbyl palmitate molecule in the rat brain.

Recent investigations have shown the ability of ascorbyl palmitate (AP), a bioactive, lipid-soluble ester of ascorbic acid (AA), to penetrate neural tissues. This study seeks to determine the occurrence of hydrolysis of AP molecule in brain tissue, which could rather point to the action of AA alone carried over the biological barrier and then released from the AP compound. The integrity of AP molecule was examined qualitatively in the rat brain by thin-layer-chromatography. AP was injected into an internal carotid artery in a dose of 75 mg per rat after tying off the common and external carotid arteries at the same side. The rats were sacrificed 15 min later, the brain tissue was extracted with chloroform/methanol and chromatographed. The AP bands plated from the samples ipsilateral to the injection side strictly corresponded to the AP standard's location and were clearly separated from the AA standard with no overlap. The experiment showed that AP resists hydrolysis in the brain and thus the short-term biological effects of AP may be ascribed to the action of an intact ester molecule. The results may help elucidate the biological action of AP, a compound that increasingly attracts attention for biomedical use due to its antioxidant potential and ability to penetrate into the membrane signaling target sites.

Hypoxic ventilatory profile in the anesthetized rat.

In the present study we investigated whether hypocapnia that accompanies hypoxic hyperventilation might affect the biphasic, stimulatory/depressant, ventilatory response to hypoxia. The experiments were carried out in anesthetized, vagotomized, spontaneously breathing, and poikilocapnic rats. The animals were subjected to acute steady-state hypoxia consisting of 12% O(2) in N(2) in inspiratory mixture. Ventilation and its frequency and volume components were assessed from the integrated electromyographic activity of the diaphragm. We found that despite the development of significant hypocapnia, the hypoxic ventilatory response consisted of rapid stimulation followed by a gradual decline. The frequency component contributed more to the ventilatory increase than that of volume. The results indicate that the hypoxic ventilatory profile in the anesthetized poikilocapnic rat resembles that known to be present during isocapnia. We conclude that hypocapnia neither hampers the hypoxic ventilatory reactivity nor alters the biphasic hypoxic ventilatory profile. These observations may aid planning experimental rat model studies.

The aging carotid body.

The respiratory system is subject to the aging process, which could limit its responsiveness to hyperventilatory stimuli. Attenuation of the ventilatory response to hypoxia in old age is, as yet, an unresolved issue. Such attenuation may be germane for the pathogenesis of respiratory disorders developing more often in elderly subjects. The aim of this study was to determine the potential adverse effects of age on the morphology and function of carotid bodies. Morphology was studied at the level of electron microscopy on carotid bodies dissected from adult young (3 months) and old (>2 years) rats and function by comparing the hypoxic ventilatory response in populations of young (mean age 24 years) and old (mean age 71 years) female subjects. The human protocol consisted of a progressive hypoxia test, based on a rebreathing technique in a closed system. The hypoxic ventilatory response was evaluated from the slopes of minute ventilation on arterial oxygen saturation. The results of the morphological study showed degenerative changes developing with age in the ultrastructure of carotid bodies. On the other side, respiratory responses to hypoxia in old women were well preserved and were no less than those in young women. Therefore, a discrepancy appeared between the morphological and functional aspects. These findings suggest development of compensatory mechanisms in brain respiratory areas which maintain primary defensive reflexes, such as the hyperventilation of hypoxia.

Oxygen breathing and ventilation.

We investigated the ventilatory response to normobaric poikilocapnic hyperoxia in healthy subjects. The study was carried out in 26 subjects of the mean age 26 +/- 0.9 (SE) years, who breathed pure oxygen through a two-way valve for 10 min. The subjects were in the sitting position with a mouthpiece and nose clip attached. Ventilatory flow was recorded using a pneumotachograph and minute ventilation was calculated from the tidal and frequency components. The SaO(2) and alveolar CO(2) tension were continuously monitored. Ten of the same subjects constituted a control group in which room air was substituted for oxygen and the tests repeated in the same way at another occasion. We found that oxygen breathing caused a transient 8.4% decline in ventilation, whose nadir was 1 min after the introduction of oxygen. Thereafter, ventilation increased significantly above the baseline value and showed a further rising tendency toward the end of the test. We conclude that acute oxygen treatment is unlikely to have a major inhibitory effect on the carotid body-dependent ventilatory drive in normal subjects. The determinants of the hyperoxic ventilatory stimulation remain to be established in further studies.

Increased local vascular endothelial growth factor expression associated with antitumor activity of proteasome inhibitor.

Inhibition of the proteasome, a multicatalytic proteinase complex, is an attractive approach to cancer therapy. Here we report that a selective inhibitor of the chymotrypsin-like activity of the proteasome, PSI (N-benzyloxycarbonyl-Ile-Glu(O-t-butyl)-Ala-leucinal) may inhibit growth of solid tumors not only through apoptosis induction, but also indirectly--through inhibition of angiogenesis. Two murine tumors: colon adenocarcinoma (C-26) and Lewis lung carcinoma (3LL) were chosen to study the antitumor effect of PSI. In an in vivo model of local tumor growth, PSI exerted significant antitumor effects against C-26 colon carcinoma, but not against 3LL lung carcinoma. Retardation of tumor growth was observed in mice treated with both 10 nmoles and 100 nmoles doses of PSI and in the latter group prolongation of the survival time of tumor-bearing mice was observed. PSI inhibited angiogenesis in the C-26 growing tumors with no such effect in 3LL tumors. Unexpectedly, that activity was associated with upregulation of vascular endothelial growth factor (VEGF) at the level of mRNA expression and protein production in C-26 tumors treated with PSI. C-26 cells treated with PSI produced increased amounts of VEGF in vitro in a dose- and time-dependent manner. We demonstrated that in C-26 colon adenocarcionoma higher VEGF production may render endothelial cells susceptible to the proapoptotic activity of PSI and is associated with inhibition of tumor growth.

Ascorbic acid enhances hypoxic ventilatory reactivity in elderly subjects.

The reducing properties of ascorbic acid in the carotid body make it a likely modifier of hypoxia-sensing mechanisms. This open-label study aimed to determine the effect of ascorbic acid on the hypoxic ventilatory response (HVR) in a population of elderly women, in whom both hypoxic reactivity and ascorbic acid levels may be deficient. We examined the HVR to progressive eucapnic hypoxia in 18 healthy females aged 60-80 years, before and after 10 days' ascorbic acid supplementation, given as a sustained release preparation of 1 g twice daily. Respiratory variables were recorded breath by breath, and hypoxic sensitivity was assessed from the linear slopes of minute ventilation and mouth occlusion pressure plotted against oxygen saturation. We found that ascorbic acid increased the HVR by a mean of 44%, this effect being driven by a higher occlusion pressure. We conclude that augmentation of hypoxic reactivity by ascorbic acid may have therapeutic potential in pathologies associated with hypoxia, which frequently develop in old age.

Ventilatory response to hypoxia in elderly women.

BACKGROUND: The respiratory system is subject to the ageing process, which could limit its responsiveness to stimuli. Attenuation of the ventilatory response to hypoxia in old age is, as yet, an unresolved issue. Such attenuation may be germane to the pathogenesis of hypoxic respiratory disorders developing more often in elderly subjects. AIM: The study seeks to determine the potential adverse effects of age on the hypoxic ventilatory response by comparing this response in groups of elderly and young female subjects. SUBJECTS AND METHODS: Nineteen healthy women of the mean age of 71+/-1.3 (SE) years and 16 women in their twenties were required to perform a progressive isocapnic hypoxic test, based on the rebreathing technique. The ventilatory response was evaluated from the slopes of minute ventilation and mouth occlusion pressure, an index of inspiratory neuromuscular drive, against arterial oxygen saturation. The breathing pattern components also were measured with the breath-by-breath routine. RESULTS: Ventilatory response to hypoxia averaged 0.65+/-0.10 L/min/% SaO(2) and neuromuscular output was 0.012+/-0.002 kPa/% SaO(2) in the elderly women and these slopes were not reduced compared with those in the young. Nor did the ventilatory slopes relate to age in the older subjects. Baseline breathing pattern was modified in the elderly in that the mean inspiratory flow was significantly higher, but it reached the same stimulated level as that in the young. CONCLUSIONS: Ventilatory response to hypoxia is independent of age in healthy women. Thus, functional sensitivity of the respiratory control mechanisms does not attenuate with age.

Cortical activity during hypoxic hyperventilation.

This study seeks to determine the pattern of electroencephalogram changes during stimulatory ventilatory responses to acute progressive hypoxia. Electroencephalograms were recorded in the 10-20 electrode system during progressive poikilocapnic hypoxic tests based on the rebreathing routine. Healthy subjects were used for he study. A major finding was that hypoxia decreased the power spectra of the alpha activity. The decrease was surprisingly rapid and greater at mild hypoxic desaturation when pulmonary ventilation was about to pick up than during the maximum hypoxic hyperventilation. The possible relation of hypoxic decline in brain bioactivity to the manifestation of hypoxic hyperventilation remains to be elucidated in further studies.

Antitumor activity of tributyrin in murine melanoma model.

Butyric acid has been known to inhibit growth and to induce differentiation of a variety of tumor cells. Butyrate-treated tumor cells have also been observed to undergo apoptosis. Although butyrate compounds have demonstrated antitumor activity in murine tumor models and have already been admitted to clinical trials in tumor patients, the exact mechanism of their antitumor effects has not been elucidated. The results of our study showed antitumor activity of tributyrin, a butyric acid prodrug, in murine melanoma model and are strongly suggestive that antiangiogenic effects could participate in antitumor effects of butyrate compounds in vivo.