CD200:CD200R Interactions and Their Importance in Immunoregulation.

The molecule CD200, described many years ago as a naturally occurring immunomodulatory agent, capable of regulating inflammation and transplant rejection, has attracted additional interest over the past years with the realization that it may also serve as an important marker for progressive malignancy. A large body of evidence also supports the hypothesis that this molecule can contribute to immunoregulation of, among other diseases, infection, autoimmune disease and allergy. New data have also come to light to characterize the receptors for CD200 (CD200R) and their potential mechanism(s) of action at the biochemical level, as well as the description of a novel natural antagonist of CD200, lacking the NH2-terminal region of the full-length molecule. Significant controversies exist concerning the relative importance of CD200 as a ligand for all reported CD200Rs. Nevertheless, some progress has been made in the identification of the structural constraints determining the interaction between CD200 and CD200R, and this information has in turn proved of use in developing novel small molecule agonists/antagonists of the interaction. The review below highlights many of these newer findings, and attempts to place them in the broad context of our understanding of the role of CD200-CD200R interactions in a variety of human diseases.

Two Sides to the Same Coin-Cytotoxicity vs. Potential Metastatic Activity of AgNPs Relative to Triple-Negative Human Breast Cancer MDA-MB-436 Cells.

Silver nanoparticles (AgNPs) are used in many fields of industry and medicine. Despite the well-established antimicrobial activity, AgNPs are foreseen to be used as anticancer drugs due to the unusual feature-inability to induce drug resistance in cancer cells. The aim of the study was to assess biological activity of AgNPs against MDA-MB-436 cells. The cells were derived from triple-negative breast cancer, a type of breast cancer with poor prognosis and is particularly difficult to cure. AgNPs were toxic to MDA-MB-436 cells and the probable mechanism of toxicity was the induction of oxidative stress. These promising effects, giving the opportunity to use AgNPs as an anti-cancer agent should, however, be treated with caution in the light of further results. Namely, the treatment of MDA-MB-436 cells with AgNPs was associated with the increased secretion of several cytokines and chemokines, which were important in breast cancer metastasis. Finally, changes in the actin cytoskeleton of MDA-MB-436 cells under the influence of AgNPs treatment were also observed.

Organophosphorus pesticides can influence the development of obesity and type 2 diabetes with concomitant metabolic changes.

Widespread use and the bioaccumulation of pesticides in the environment lead to the contamination of air, water, soil and agricultural resources. A huge body of evidence points to the association between the pesticide exposure and increase in the incidence of chronic diseases, e.g. cancer, birth defects, reproductive disorders, neurodegenerative, cardiovascular and respiratory diseases, developmental disorders, metabolic disorders, chronic renal disorders or autoimmune diseases. Organophosphorus compounds are among the most widely used pesticides. A growing body of evidence is suggesting the potential interdependence between the organophosphorus pesticides (OPs) exposure and risk of obesity and type 2 diabetes mellitus (T2DM). This article reviews the current literature to highlight the latest in vitro and in vivo evidences on the possible influence of OPs on obesity and T2DM development, as well as epidemiological evidence for the metabolic toxicity of OPs in humans. The article also draws attention to the influence of maternal OPs exposure on offspring. Summarized studies suggest that OPs exposure is associated with metabolic changes linked with obesity and T2DM indicated that such exposures may increase risk or vulnerability to other contributory components.

Lower weight gain after vaping cessation than after smoking quitting

Background: Smoking is frequently a way to control appetite and weight. The data concerning the body mass gain after quitting among the users of electronic cigarettes who have no prior history of smoking traditional cigarettes is inconsistent. Objective: In our study we have compared smoking and vaping impact on weight gain and glycaemia. Material and methods: 3 groups of rats were used. The group A was exposed to vapour and group B were exposed to smoke. Rats in the group C constituted the control group without nicotine exposition. Results: During 6 weeks of experiment weight gain of rats in the A and B groups was comparable, while animals from group C had gained signifi0cantly more. During 2 weeks after cessation of exposition to nicotine animals from group B gained more weight than rats of A and C group. Blood glucose was higher in group B than in groups A and C 24 h after last exposure to nicotine and 2 weeks after nicotine exposure cessation. Conclusion: Effects of vaping on weight increase is similar to smoking, but after vaping cassation weight gain is lower and comparable with nicotine nonusers.

CB2R agonist prevents nicotine induced lung fibrosis.

INTRODUCTION: Nicotine stimulates fibroblast proliferation while increasing inflammation and fibrosis of tissues. The cannabinoid receptor 1 (CB1R) is mainly located in the CNS, while cannabinoid receptor 2 (CB2R) is located in the immune cells within the body. CB2R regulates inflammatory processes and fibroblast function. PURPOSE: We investigated the impact of CB2R agonist, JWH 133 and the antagonist, AM630 on lung tissue, applied directly before nicotine application. MATERIAL AND METHODS: 40 mice were placed into 4 groups. The experimental groups received nicotine intraperitoneally at a dose of 0.05 mg/kg of body weight (BW) for 14 days. Group B also received AM630 (0.5mg/kg of BW), while Group A was administered with JWH133 (1 mg/kg of BW). Group N received nicotine alone. The Control group C received 0.9% NaCl. After decapitation, lung tissues were stained with H&E, Trichrome Masson's method, and IHC against CTGF and α-SMA. The digital image processing system Image J with the IHC profiler plugins was then employed, optical density and IHC optical density score were calculated. RESULTS: In the N group, an increase in the thickness of alveolar spaces (9.16 SD4.95µm vs. 4.77SD2.99µm in the C group), leukocytes infiltration and collagen deposition has been observed(OD: 0.20 SD0.0vs 0.07SD0.04 in the C group). In the B group, the alveolar space thickness has been the highest (11.57SD8.13µm). Furthermore, in this group, hyperaemia, destruction of lung structure, hyperplasia of II type pneumocyte and interstitial fibrosis has been observed (OD: 0.23 SD0.08). In contrast, the lung tissue of the A group has had normal structure and the thinnest alveolar septum (3.88 SD2.64µm). The expression of CTGF and α-SMA has been the highest in the B group. CONCLUSION: Nicotine induces interstitial lung fibrosis that is enhanced by the CB2R antagonist and diminished by the CB2R agonist. Therefore, the CB2R agonist may offer a protection against fibrosis.

Decrease in Lipid Droplets in Adrenal Cortex of Male Wistar Rats after Chronic Exposure to Energy Drinks.

Background and objectives: Energy drinks are popular non-alcoholic beverages. They are consumed in large amounts, mainly by active, young people. Although they are easily accessible and marketed as safe, numerous cases of adverse effects have been published, including cardiac arrest, arrythmias, acute hepatitis, and renal failure. The aim of the current study is the assessment of energy drink influence on the histological structure of adrenal cortex in rats. Material and Methods: 15 male young Wistar rats were equally divided into three groups: control (C), experimental (E) and reversibility control (RC). C group received water and standard rodent food ad libitum while both E and RC groups had additionally unlimited access to energy drinks. C and E groups were decapitated after 8 weeks and RC was given another 8 weeks without energy drinks. Adrenal glands were embedded in paraffin blocks and 5 µm slides were prepared and stained according to standard H&E and Masson's trichrome protocols. Additionally, immunohistochemical stainings against Ki-67, p53, CTGF and caspase-3 were prepared. Results: Decreased vacuolization and numerous pyknotic nuclei were noted in E and RC groups. Overexpression of caspase-3 was noted both subcapsular in zona glomerulosa and along sinusoids in zona fasciculata. Increased collagen deposition in zona glomerulosa and zona fasciculata of E and RC was observed. Insular and irregular overexpression of CTGF was noted. The overall picture of CTGF expression matched the Masson's trichrome. No significant difference was observed in Ki-67 expression. Conclusions: The results of the current study suggest that the stimulation is so intense that it causes significant damage to adrenal cortical cells, resulting in their apoptosis. It seems, however, that the observed effects are at least partially reversible.

Dietary supplements ­ consumer assessment based on questionnaire survey

INTRODUCTION: Dietary supplements (DS) are dietary products aiming only at diet complementation. Nevertheless, they are frequently used in treatment of various conditions since they are safer substitutes for medication. AIM OF THE STUDY: The aim of this study was to analyze the frequency of dietary supplements using by young people, their knowledge about the used substances, and the assessment of the effectiveness of DS by those who consumed these products. MATERIALS AND METHODS: The present study was conducted by the means of an anonymous questionnaire assessed the DS intake among subjects aged between 15 and 54. The questionnaire was performed both on-line among 611 subjects and in paper form among 242 1st year medical students of Medical University of Lublin. The average age of the participants was 22.02 ± 3.74 years. Women constituted 72.92% of all respondents. RESULTS: DS consumption was reported by most questionnaire participants, that is 77. 84%. The supplements were purchased mainly in pharmacies (81.63%). 47.87% of the respondents, declared to be aware of the undesirable side effects of DS, and 67.29% claimed to be able to distinguish between a medication and a supplement. 20.48% of the respondents reported a significant improvement of their condition resulting from DS usage, 51.05% reported a partial improvement, and 28.46% observed no difference. CONCLUSIONS: Dietary supplements are commonly consumed by young people regardless of the fact that many do not observe any DS intake-related improvement of their health. The knowledge about the effects of dietary supplements and their adverse effects is relatively high. Yet, many people do not know the difference between a medication and DS. The knowledge concerning the risks of DS misuse should be promoted among young people in particular.

EMT promoting transcription factors as prognostic markers in human breast cancer.

PURPOSE: Breast cancer is one of the most common female cancers. Moreover, despite the progress in medicine, its mortality rate is still very high. Therefore, researchers are constantly looking for new prognostic factors, which may simplify disease diagnosis and optimize the therapy. Metastases are responsible for the majority of deaths caused by breast cancer. Epithelial-mesenchymal transition is one of the mechanisms of metastasis, which is controlled by specific transcription factors. In the recent years, many researchers studied the prognostic value of factors promoting the epithelial-mesenchymal transition in patients with breast cancer. This work is an attempt to summarize the current state of knowledge on this issue. METHODS: A systemic search of peer-reviewed articles published between November 2005 and February 2016 was performed using PubMed/MEDLINE database. Most cited articles constituted original papers, although single review articles were also included. RESULTS: Based on the so far conducted studies, a promising conclusion can be drawn, that several described factors might serve as a putative negative prognostic marker in breast cancer. CONCLUSIONS: Obtained results of this review should encourage researchers to conduct further clinical trials on large patient groups which will evaluate the prognostic value of EMT transcription factors in breast cancer course.

Tobacco smokers and electronic cigarettes users among Polish universities students.

BACKGROUND: Electronic cigarettes (e-cigarettes) are small battery-powered electronic devices, heating the liquid to produce vapour--in most cases the latter contains nicotine and several flavourings. E-cigarettes are highly advertised across the media, mainly as healthy substitute to conventional cigarettes, aid in quitting smoking addiction or way of circumventing ban on smoking in public places. OBJECTIVE: The aim of study was obtaining epidemiological data on cigarette smoking and electronic cigarette usage among Polish universities students. MATERIAL AND METHODS: Students of different Polish state universities were asked to fill a self-prepared survey on cigarette-smoking and electronic cigarette usage. 1068 fulfilled questionnaires were gathered. The population was divided into two subgroups--medical universities' students (n=545) and non-medical universities students (n=523). RESULTS: 23.78% of respondents declared current smoking while 57.0% admitted ever smoking. The mean duration of smoking among current smokers was 4.17±2.53 years. 56.30% of current smokers tried quitting at least once. 31.46% of students declared ever using e-cigarettes (37.28% (n=195) among non-medical universities' students and 25.87% (n=141) among medical universities' students and 8.33% current usage. Among the latter 52.81% admitted simultaneous smoking. 26.97% of current e-cigarettes' users declared having experienced side effects of e-cigarettes. 42.70% (n=456) of respondents viewed e-cigarettes as safer than conventional cigarettes, this group comprises of 40.54% (n=212) non-medical and 44.77% (n=244) medical universities' students. 85.39% (n=912) of students viewed e-cigarettes as generally unhealthy, there were 83.56% (n=437) non-medical and 87.16% (n=475) medical universities' students among this group. CONCLUSIONS: The frequency of e-cigarettes usage resembles current status in many Western countries. Collected data shows high frequency of e-cigarettes usage and conventional cigarettes smoking among students (also medical universities' students). The situation requires intensive preventive measures to limit and reduce the popularity of tobacco products along with modern equivalents like electronic cigarettes.

Analysis of Polish internet retail sites offering electronic cigarettes.

BACKGROUND: Electronic cigarettes as possibly healthier alternative to conventional cigarettes are gaining popularity worldwide, although they are still hazardous to human health. Partly it is caused by unregulated advertising and online sales. Unfortunately it is more and more popular for youth to try electronic cigarettes. OBJECTIVE: The aim of the study was to assess the marketing claims used by Polish websites offering electronic cigarettes. MATERIAL AND METHODS: A search using Google search engine was performed in July 2015 for two keywords: e-papierosy [e-cigarettes] and elektroniczne papierosy [electronic cigarettes]. First 150 websites (15 pages) were listed. After initial review 86 pages met all inclusion criteria and were included in the study. Pages were searched for presence of 13 selected marketing claims as well as age-related warning and any social websites connections. RESULTS: Age-related warning was present on only 33.72% (n=29) websites. Two thirds has its own Facebook fan-page with average 1922.09 ± 3634.86 likes. Articles about health are available on 10.46% (n=9) websites, 53.49% (n=46) states that e-cigarettes are healthier than conventional ones, 39.53% (n=34) emphasized that during usage of e-cigarettes no tarry substances are produced. Two pages had special article in which conventional and electronic cigarettes were compared. Almost half (44.19%) remarked that e-cigarettes are cheaper in usage than conventional, one third pointed out the simplicity of usage. 32.56% advertised e-cigarettes as aid in quitting smoking. One fourth stated that e-cigarettes are harmless for surroundings. 33.72% marketed them as a way of bypassing public smoking act. 56.98% remarked the variety of liquid tastes offered. CONCLUSIONS: Electronic cigarettes and their rising popularity create another new possible threat for public health as the widely available information emphasize safety of e-cigarettes usage and as their availability and usage is not limited or restricted by law. KEY WORDS: electronic cigarettes, e-cigarettes, internet retail websites.

Intrinsic apoptosis pathway in fallopian tube epithelial cells induced by cladribine.

Cladribine is a purine nucleoside analog which initiates the apoptotic mechanism within cells. Moreover, the available data confirms that cladribine, with the participation of the p53 protein, as well as the proapoptotic proteins from the Bcl-2 family, also induces the activation of the intrinsic apoptosis pathway. However, while there has been a lot of research devoted to the effect of cladribine on lymphatic system cells, little is known about the impact of cladribine on the reproductive system. The aim of our study was to evaluate apoptosis in oviduct epithelial cells sourced from 15 different female rats. In so doing, the sections were stained with caspases 3, 9, and 8. Results suggest that cladribine also induces apoptosis in the oviduct epithelial cells by way of the intrinsic pathway. Indeed, the discontinuing of the administration of cladribine leads to a reduction in the amount of apoptotic cells in the oviduct epithelium.

Changes in the Histological Structure of Adrenal Glands and Corticosterone Level after Whey Protein or Bee Pollen Supplementation in Running and Non-Running Rats.

Due to the many health-promoting properties of bee pollen and whey protein, both products are widely used as dietary supplements. According to these reports on their health-promoting properties, the aim of our study is to assess whether these products can influence the structure and function of the adrenal glands in rats. Thirty male Wistar rats were divided into six equal groups. Among them, there were three groups which included non-running rats and three groups which included running rats. Both of these running (n = 3) and non-running (n = 3) groups included non-supplemented (control groups), bee-pollen-supplemented groups, and whey-protein-supplemented groups. After 8 weeks, the rats were decapitated, their adrenal glands were collected, and paraffin slides were prepared. Then, staining according to the standard H&E and Masson's trichrome protocols was performed. Fecal and urine samples were collected prior to the end of the study to measure corticosterone levels. In the group of non-running rats, the consumption of bee pollen was noted to be significantly higher when compared to the group of running rats (p < 0.05). The thickness of the particular adrenal cortex layers was similar among all of the groups (p > 0.05). The statistically significant changes in the microscopic structure of the adrenal glands, especially regarding cell nuclei diameter and structure, as well as the architecture of sinusoids, were observed between the groups. Moreover, urine corticosterone concentrations were found to vary between all of the analyzed groups (p < 0.05). These results indicate that both bee pollen and whey protein have limited stress-reducing potential.

All That Glitters Is Not Gold: Assessment of Bee Pollen Supplementation Effects on Gastric Mucosa.

The aim of this study was to assess the influence of bee pollen supplementation on the levels of enzymes important for gastric mucosal homeostasis, namely cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and a biomarker-asymmetric dimethylarginine (ADMA)-in the gastric mucosa of Wistar rats. The experimental phase divided the rats into four groups: two control groups, sedentary and active, both not supplemented, and two experimental groups, sedentary and active, supplemented with bee pollen. The results indicated that bee pollen supplementation reduced the levels of COX-1 and elevated iNOS levels, while showing no significant impact on COX-2 levels. These findings do not conclusively support the gastroprotective and anti-inflammatory effects of bee pollen on gastric mucosa. However, the supplementation could have resulted in reduced ADMA levels in the physically active supplemented group. Our study does not unequivocally demonstrate the positive effects of bee pollen supplementation on the gastric mucosa, which may be attributed to the specific metabolism and bioavailability of substances within unprocessed, dried bee pollen. Further research should explore the topic of potential therapeutic applications of bee pollen in gastrointestinal health and its interactions with ADMA signaling pathways.

Different effects of resveratrol on dose-related Doxorubicin-induced heart and liver toxicity.

The aim of the study was to evaluate the effect of resveratrol in doxorubicin-induced cardiac and hepatic toxicity. Doxorubicin was administered once a week throughout the period of 7 weeks with 1.0 or 2.0 mg/kg body weight or concomitantly with resveratrol (20 mg/kg of feed). Heart and liver toxicity was histologically and biochemically evaluated. Resveratrol protected from the heart lipid peroxidation caused by 1 mg doxorubicin and it sharply diminished superoxide dismutase activity. An insignificant effect of resveratrol on the lipid peroxidation level and the superoxide dismutase activity was observed in the hearts of rats administered a higher dose of doxorubicin. However, resveratrol attenuate necrosis and other cardiac histopathological changes were induced by a high dose of doxorubicin. Interestingly, it slightly intensified adverse cardiac histological changes in rats receiving a lower dose of doxorubicin. Resveratrol did not have any protective effect on the hepatic oxidative stress, while exerting a mild beneficial effect on the morphological changes caused by doxorubicin. All in all, this study has shown different effects of resveratrol on dose-related doxorubicin-induced heart and liver toxicity. Resveratrol may modulate the hepatic and cardiac effect of doxorubicin, depending on the drug dose.

Changes in Histological Structure, Interleukin 12, Smooth Muscle Actin and Nitric Oxide Synthase 1. and 3. Expression in the Liver of Running and Non-Running Wistar Rats Supplemented with Bee Pollen or Whey Protein.

Introduction: Bee pollen is a natural substance obtained from flowers by bees. It is a rich source of protein, vitamins and minerals. It can be used as a dietary supplement. Bee pollen has been investigated for the treatment of some diseases with promising potential. It can be helpful in supportive therapy for dyslipidemia, metabolic syndrome, diabetes type 2, as well the prevention and control of coronary heart disease and myocardial infarction. Whey protein is a rich source of amino acids. It is a basic dietary supplement for many athletes, both professional and amateur. It stimulates muscle growth and provides nutrition for cachectic patients. Aim of the study: The objective of the study was to assess the impact of dietary supplementation of bee pollen or whey protein on the Wistar rat liver histological structure and expression of interleukin 12, smooth muscle actin and nitric oxide synthases among running and non-running rats. Material and methods: Thirty male Wistar rats were divided into six equal groups, three running and three non-running. Among both there was one control, one supplemented with bee pollen and one receiving whey proteins. After 8 weeks, all animals were decapitated and their livers were collected. Five micrometer thick slides were prepared and used for classical histological staining and immuno-histochemistry. ImageJ image analysis software was used to measure optical density and immunohistochemistry profile coverage. Results: Among all groups, morphology of liver was similar. In the running control group, expression of interleukin-12 (IL-12) was decreased as well as expression of endothelial nitric oxide synthase (eNOS) in a group of bee pollen supplemented rats. No significant changes in α- smooth muscle actin (α-SMA) expression was observed. Conclusions: Bee pollen is proving to be a questionable choice for athletes as an alternative to whey protein. Bee pollen supplementation affects hepatocyte cellular activity and has hepatoprotective effects. Whey protein performs worse in this regard. Lower antioxidant properties were found in groups supplemented with bee pollen than with whey protein.

Major regulators of microRNAs biogenesis Dicer and Drosha are down-regulated in endometrial cancer.

Alterations in microRNAs expression have been proposed to play role in endometrial cancer pathogenesis. Dicer and Drosha are main regulators of microRNA biogenesis and deregulation of their expression has been indicated as a possible cause of microRNAs alterations observed in various cancers. The objective of this study was to investigate Dicer and Drosha genes expression in endometrial cancer and to analyze the impact of clinicopathological characteristics on their expression. Fresh tissue samples were collected from 44 patients (26 endometroid endometrial carcinoma and 18 controls). Clinical and pathological data were acquired from medical documentation. Dicer and Drosha genes expressions were assessed by qRT-PCR using validated reference genes. Dicer and Drosha expression levels were significantly lower in endometrial cancer samples comparing to controls. Dicer was down-regulated by the factor of 1.54 (p=0.009) and Drosha gene mean expression value was 1.4 times lower in endometrial cancer group versus control group (p=0.008). Down-regulation of Dicer significantly correlated with decreased expression of Drosha (coefficient value 0.75). Decreased expression of Drosha correlated with higher histological grade and was influenced by BMI. Lower Dicer expression was found in nulli- and uniparous females comparing to multiparous individuals (p=0.002). Neither the FIGO stage nor the menstrual status had significant influence on the expression of studied genes. This study revealed for the first time that expression alterations of main regulators of microRNAs biogenesis are present in endometrial cancer tissue and could be potentially responsible for altered microRNAs profiles observed in this malignancy.

Lung histomorphological alterations in rats exposed to cigarette smoke and electronic cigarette vapour.

Electronic cigarettes are becoming increasingly common as a form of nicotine usage, known as vaping. Numerous studies have demonstrated that using electronic cigarettes may lead to nicotine dependence and has a potentially harmful impact on health. The present study compared the impact of electronic and conventional cigarettes on lung tissue. The experiment included 30 male Wistar rats. The animals were divided into three groups: Group A was exposed to electronic cigarette liquid vapour; group B to conventional smoke; and group C constituted the control group without exposition to the nicotine. In both experimental groups numerous alterations were observed, including a collapse of parenchyma, hyperhagia, hyperplasia of type II of pneumocytes, collagen deposition and an increased number of macrophages within thickened alveolar septa. Additionally, an initial elastolysis was observed. The elastic fibers were disrupted, sparse, irregular and thickened, whereas the numbers of α-SMA positive myofibroblasts and blood vessels were highest in the group exposed to conventional cigarette smoke. In conclusion, the usage of the electronic cigarettes leads to milder pathological alterations compared with traditional cigarette smoking. Nevertheless, the histopathological damage caused by vaping may lead to the development of alterations in the lung tissue which consequently hinder gas exchange.

Susceptibility of HepG2 Cells to Silver Nanoparticles in Combination with other Metal/Metal Oxide Nanoparticles.

The fast-growing use of nanomaterials in everyday life raises the question about the safety of their use. Unfortunately, the risks associated with the use of nanoparticles (NPs) have not yet been fully assessed. The majority of studies conducted so far at the molecular and cellular level have focused on a single-type exposure, assuming that NPs act as the only factor. In the natural environment, however, we are likely exposed to a mixture of nanoparticles, whose interactions may modulate their impact on living organisms. This study aimed to evaluate the toxicological effects caused by in vitro exposure of HepG2 cells to AgNPs in combination with AuNPs, CdTe quantum dot (QD) NPs, TiO2NPs, or SiO2NPs. The results showed that the toxicity of nanoparticle binary mixtures depended on the type and ratio of NPs used. In general, the toxicity of binary mixtures of NPs was lower than the sum of toxicities of NPs alone (protective effect).

Granular Cell Tumor in a Horse: Multifocal Pulmonary Distribution and Evidence of Autophagy in Tumorigenesis.

Granular cell tumor (GCT) is a soft tissue neoplasm characterized by abundant intracellular eosinophilic granules. The majority of GCTs are benign, although some display malignant behavior. Furthermore, GCTs may mimic other neoplasms. The clinical course and biology of GCTs are poorly understood. Regarding the histogenesis of GCT, a Schwann cell origin is currently favored in light of immunohistochemical and ultrastructural analyses. However, based on literature data, some of the primitive GCTs show non-neural origin; therefore, the histogenesis of this tumor has remained enigmatic. Granular cell tumors can arise in almost any location of the body and typically present as solitary lesions. This study illustrates equine primary GCT with multifocal pulmonary distribution. The presence of GCT in the respiratory tract becomes a diagnostic challenge on initial presentation. The morphologic details of this case are presented. Immunohistochemical evaluation confirmed the neuronal origin of equine GCT and the relation of intracytoplasmic granules formation to an autophagy phenomenon. Most of the discussion is related to GCT nature to help characterize molecular aspects associated with the biological behavior of this tumor and its heterogeneity.

Expression of caspase 1 and histomorphology of lung after cladribine treatment.

BACKGROUND: Cladribine is a useful immunosuppressive drug for the treatment of autoimmune diseases, leukemias and multiple sclerosis (MS). Despite the drug having low toxicity, side effects have been reported connected with myelosuppression, neutropenia and severe anemia. OBJECTIVES: The objective of this study was to investigate the influence of cladribine on lung pathomorphology and the expression of caspase 1 using immunohistochemistry method. MATERIAL AND METHODS: The study was conducted on Wistar rats, which were divided into a control group (C) and an experimental group (E). In group C, the rats were given a 0.9% NaCl solution by a subcutaneous injection, at the same dose as the dose of drug used in the experiment. In group E, the animals received cladribine at a dose of 0.07 mg/kg/24 h by a subcutaneous injection. The animals were decapitated 24 h following the last dose. To detect collagen deposition, we utilized Masson's trichrome staining. To evaluate the intensity of the inflammatory process in the lung, an immunohistochemistry reaction was carried out with the use of caspase 1. RESULTS: In group E, we observed an increase in the thickness of space between the alveoli. A statistically significant (p < 0.017243) difference between the thicknesses of the interalveolar septum was seen between the research groups. In E group, we observed regions with collagen deposition, alveolar epithelial cell hyperplasia, hyperemia and inflammatory cell infiltration. Caspase 1 activity was higher in group E. The immunohistochemical reaction with caspase 1 was positive in 49% of all the interalveolar cells in group E; however, in group C about 13% of the interalveolar cell showed positive immunohistochemistry (IHC) response. CONCLUSIONS: Cladribine-based therapy might have negative influence on lung morphology. The interstitial changes in the lung tissue suggest that cladribine is a drug that may be the cause of drug-induced lung disease and may lead to several respiratory disorders.