Foot static disturbances and clinical features in overweight patients with rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA) is a chronic, inflammatory, connective tissue disease, leading to foot deformities, impairment of locomotive functions, and reducing patients' quality of life. Obesity prevalence is rising in early RA and is associated with worse disease activity, function and health-related quality of life, with a significant negative impact on achieving a low Disease Activity Score in 28 joints (DAS28). The aim of the study was to evaluate foot deformities in overweight RA patients according to the severity of the disease. Material and methods: The study was performed on 50 overweight women with RA. The control group consisted of 50 overweight women free of any disorders. Plantography examination was carried out by means of a CQ ST 2K podoscope. Rheumatoid arthritis disease activity was assessed by DAS28. Activity limitation was assessed using the Health Assessment Questionnaire (HAQ) and foot posture by the Foot Posture Index (FPI-6). Body composition analysis was performed using In Body 220. Results: Hallux valgus was the most frequent deformation in RA patients with overweight. Longitudinal flat foot was much more frequent in RA patients than transverse flat foot. A relationship between fat tissue mass and presence of transverse flat foot in RA patients with overweight was found. In this group DAS28, VAS, and Clarke's angle were correlated with increased value of HAQ. Conclusions: Plantar contourography showed a trend of an increase of α angle values and the Sztriter-Godunow index (KY) in overweight RA patients with increasing severity of radiological changes and DAS28, requiring use of proper prevention and therapeutic strategies of destructive changes.

Gender and Work Experience as Moderators of Relations between Management Level, Physical Activity, Eating Attitudes, and Social Skills of Managers during the COVID-19 Pandemic.

Being employed in a managerial position is often associated with maintaining high standards in many aspects of life. Many leaders pay attention to their physical activity, eating habits, and social skills. The onset of the COVID-19 pandemic brought additional difficulties to the already-demanding job of managing people and forced managers to make many changes to their daily functioning at work. The main goal of this study was to establish whether Gender, Experience, and Management Level influenced respondents' healthy behaviors (eating attitudes and physical activity) or soft skills during the COVID-19 pandemic. This study was carried out during the COVID-19 pandemic with a sample of 348 managers from a variety of companies (n = 222 women, n = 126 men) with different levels of experience and responsibility. The authors used the 26-item Eating Attitudes Test (EAT-26), four questions from the Physical Activity Objectives Questionnaire, and a self-authored soft skills questionnaire. The results showed that, compared to females, males were characterized by lower levels on all three EAT-26 scales: Bulimia and Food Preoccupation, Oral Control, and Dieting. On the other hand, male respondents who held high managerial positions were characterized by high levels of Dieting, Oral Control, Bulimia, and Food Preoccupation. This analysis provides insights that may help improve the quality of life of employees; however, further research is needed to investigate the direct influence of managers on employees in different industries.

Evaluation of the Effectiveness of Iontophoresis with Perskindol Gel in Patients with Osteoarthritis of the Knee Joints.

INTRODUCTION: Osteoarthritis (OA) is one of the most common causes of pain in the musculoskeletal system leading to disability. The basic principle of the therapy is the simultaneous use of pharmacological and non-pharmacological treatments. The aim of this study was to evaluate the effectiveness of galvanic and iontophoresis treatments with Perskindol Active Classic Gel (Perskindol) in patients with OA of the knee joints. Moreover, a comparative evaluation of the effectiveness of the application was performed depending on the selection of the active electrode. MATERIAL AND METHODS: The study included 100 patients with gonarthrosis, treated at the Rehabilitation Clinic of the Bialystok University Hospital. Three groups were randomly selected: in group I (n = 33), anodic galvanic treatment was applied, group II (n = 33) received iontophoresis with Perskindol gel from the negative pole ("-" iontophoresis), and group III (n = 34) received iontophoresis with Perskindol gel from the positive pole ("+" iontophoresis). The VAS, the Laitinen questionnaire, the Lequesne Index, the Lysholm questionnaire, and the SF-36v2 health survey were used for the clinical evaluation of the patients. RESULTS: In the group of patients who underwent iontophoresis with the use of Perskindol gel introduced from the positive pole, a statistically significant improvement was shown in all the assessed parameters in comparison to the patients who underwent anodic galvanic treatment. CONCLUSIONS: The most favorable effect of iontophoresis was observed in the case of iontophoresis with Perskindol gel introduced from the positive pole.

Static Foot Disturbances and the Quality of Life of Older Person with Rheumatoid Arthritis.

Disturbed static foot function is one of the main causes of impaired quality of life, which may be related to the frailty syndrome of older adult patients with Rheumatoid Arthitis (RA). The aim of the study was to evaluate the relationship between parameters of static foot function disturbances and quality of life of older adult patients with RA. The study was performed among 102 patients with RA diagnosed according to the American College of Rheumatology (ACR) and EULAR 2010 criteria. Patients were divided into four subgroups depending on radiological evaluation according to the Steinbrocker classification. Plantoconturography examination was conducted using a podoscope with a 3D scanner and software for computer foot examination CQ ST2K. Quality of life of patients with RA was evaluated using the Arthritis Impact Measurement Scales-2 (AIMS-2). A statistically significant relationship between AIMS-2 and parameters of static foot function disturbances was observed. The study revealed correlations between parameters of disturbed static foot function and RA severity in comparison to disease duration. Our results indicate a relationship between static foot function disturbances and quality of life of patients with RA, not only in the area of physical activity, but also in the social an emotional domain. Study results indicate that plantoconturography and assessment of quality of life using AIMS-2 could be useful as a diagnostic and prognostic tool in RA.

Systemic COVID-19 Vaccination Enhances the Humoral Immune Response after SARS-CoV-2 Infection: A Population Study from a Hospital in Poland Criteria for COVID-19 Reimmunization Are Needed.

Systemic vaccination with the BNT162b2 mRNA vaccine stimulates the humoral response. Our study aimed to compare the intensity of the humoral immune response, measured by SARS-CoV-2 IgG, SARS-CoV-2 IgM, and S-RBD-neutralizing IgG antibody levels after COVID-19 vaccination versus after SARS-CoV-2 infection. We analyzed 1060 people in the following groups: convalescents; healthy unvaccinated individuals; individuals vaccinated with Comirnaty, AstraZeneca, Moderna, or Johnson & Johnson; and vaccinated SARS-CoV-2 convalescents. The concentrations of SARS-CoV-2 IgG, SARS-CoV-2 IgM, and S-RBD-neutralizing antibodies were estimated in an oncology hospital laboratory by chemiluminescent immunoassay (CLIA; MAGLUMI). Results: (1) We observed a rise in antibody response in both the SARS-CoV-2 convalescent and COVID-19-vaccinated groups. (2) The levels of all antibody concentrations in vaccinated COVID-19 convalescents were significantly higher. (3) We differentiated asymptomatic SARS-CoV-2 convalescents from the control group. Our analysis suggests that monitoring SARS-CoV-2 IgG antibody concentrations is essential as an indicator of asymptomatic COVID-19 and as a measure of the effectiveness of the humoral response in convalescents and vaccinated people. Considering the time-limited effects of post-SARS-CoV-2 infection recovery or vaccination and the physiological half-life, among other factors, we suggest monitoring IgG antibody levels as a criterion for future vaccination.

Well-Being of High-Level Managers during the Pandemic: The Role of Fear of Negative Appearance, Anxiety, and Eating Behaviors.

(1) Background: The COVID-19 pandemic has caused unprecedented changes in the contemporary world, significantly affecting the work of companies, especially management staff. This study investigated whether fear about one's health (caused by the pandemic, disordered eating attitudes, or concerns about one's body image) has a negative relationship with the well-being of managers. (2) Methods: N = 354 managers (222 women, 126 men, and 6 people with no gender identity) participated in the study. The following psychometric instruments were used: the psychological well-being scale, the coronavirus anxiety scale, the fear of negative appearance evaluation scale, and the eating attitude test-26. Results: the fear of negative appearance influenced the well-being of the studied managers. However, this relation was mediated by dieting as well as bulimia and food preoccupation. (4) Conclusions: the well-being level depended on the managers' positive body images, but only when mediated by healthy dieting and eating attitudes. While the well-being level of managers was high, it is worth further exploring how they can flourish and develop in life and work, which can also transfer to the quality of life of their co-workers and companies. However, the subject of the well-being of managers warrants more research; for example, by considering different moderators, such as job experience, gender, and age. Moreover, experimental studies examining the effectiveness of different interventions for the physical and mental health of managers could be worth investigating.

Effects of Pegylated Interferon Alpha and Ribavirin (pegIFN-α/RBV) Therapeutic Approach on Regulatory T Cells in HCV-Monoinfected and HCV/HIV-Coinfected Patients.

Approximately 25% of HIV-infected patients are co-infected with HCV. Notably, the burden of HCV infection (e.g., viral persistence, viral load, or HCV-related liver symptoms) is more pronounced in the presence of HIV co-infection. However, to date, the underlying immune mechanisms accounting for accelerated disease progression in HIV/HCV-coinfected individuals have not been described in sufficient detail. We hypothesized that regulatory T cells (Treg) bearing potent immunosuppressive capacities could not only play a substantial role in the pathogenesis of HCV/HIV coinfection but also modulate the response to the standard anti-viral therapy. MATERIALS AND METHODS: To this end, we studied alterations in frequencies of Treg cells in correlation with other Treg-related and virus-related parameters in both HCV and HCV/HIV-infected patients subjected to standard pegIFN-α/RBV therapy. RESULTS: Notably, we found that pegIFN-α/RBV therapy significantly increased levels of Treg cells in HCV-infected but not in HIV/HCV-coinfected individuals. Furthermore, HIV/HCV-coinfection was demonstrated to inhibit expansion of regulatory T cells during anti-viral treatment; thus, it might probably be responsible for viral persistence and HCV-related liver damage. CONCLUSIONS: Therapy with pegIFN-α/RBV demonstrated a significant effect on regulatory T cells in the course of HIV and/or HCV infection indicating a crucial role in the anti-viral immune response.

Clinical usefulness of videocapillaroscopy and selected endothelial cell activation markers in people with Type 1 diabetes mellitus complicated by microangiopathy.

PURPOSE: Microvascular abnormalities are one of the most important causes of persistent diabetic complications. The aim of our study was to compare microvascular changes examined by nailfold videocapillaroscopy (NVC) examination with serum concentrations of vascular endothelial growth factor (VEGF), soluble thrombomodulin (sTM) and endothelin-1 (ET-1) in people with Type 1 diabetes with and without microangiopathy. MATERIAL/METHODS: The study included 106 people with Type 1 diabetes and 40 healthy controls. All participants were evaluated by extensive clinical, laboratory and capillaroscopic studies. NVC was performed using a stereomicroscope SZ 4045 (Olympus, Germany). The intensity of morphological changes was graded from 0 to 3. Serum levels of VEGF, sTM and ET-1 were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Morphological changes were observed by NVC in 86 out of 106 (81%) people with Type 1 diabetes mellitus. Severe capillaroscopic changes (score 3) were seen in 32 out of 54 (59%) people with microangiopathy, but in only seven out of 52 (13%) individuals without microangiopathy. Higher serum concentration of VEGF (p<0.001), ET-1 (p<0.001) and sTM (p<0.05) were demonstrated in people with diabetes complicated with microangiopathy compared to healthy controls. Moreover, comparison between people with and without microangiopathic complications showed a significantly higher capillaroscopic score and sTM serum concentration in the group with retinopathy (p<0.001) nephropathy (p<0.001) and neuropathy (p<0.01). CONCLUSIONS: Our results suggest that abnormalities in NVC may reflect the extent of microvascular involvement and associated with higher VEGF, sTM and ET-1 serum levels, as well as with microangiopathic complications in diabetic people.

Raynaud's phenomenon: new aspects of pathogenesis and the role of nailfold videocapillaroscopy.

Raynaud's phenomenon (RP) refers to paroxysmal pallor or cyanosis of the digits of the hands or feet and, infrequently, the tips of the nose or ears (acral parts) owing to cold-induced vasoconstriction of the digital arteries, precapillary arterioles, and cutaneous arteriovenous shunts. Raynaud's phenomenon reflects an exaggeration of normal central and local vasomotor responses to cold or emotion. Raynaud's phenomenon has been classified as primary or secondary, depending on whether it occurs as an isolated condition or is associated mainly with a connective tissue disease. Dysregulation of autonomic and sensitive nerve fibers, functional and structural vessel changes, and intravascular alterations can be observed in the pathogenesis of RP. Nailfold videocapillaroscopy (NVC) is the best non-invasive and repetitive diagnostic technique for detecting morpho-functional changes in the microcirculation. Nailfold videocapillaroscopy is accepted in early diagnosis and monitoring of primary and secondary RP.

Transient increase of interferon-stimulated genes and no clinical benefit by chloroquine treatment during acute simian immunodeficiency virus infection of macaques.

Simian immunodeficiency virus (SIV) infection leads to AIDS in experimentally infected Rhesus macaques similarly to HIV-infected humans. In contrast, SIV infection of natural hosts is characterized by a down-regulation of innate acute responses to the virus within a few weeks of infection and results in limited pathology. Chloroquine (CQ) has been used in the treatment or prevention of malaria and has recently been shown to cause a decrease of immune activation and CD4 cell loss in HIV-infected individuals treated with antiretroviral therapy. Here, we treated Rhesus macaques with CQ during the acute phase of SIVmac251 infection with the intent to decrease viral-induced immune activation and possibly limit disease progression. Contrary to what was expected, CQ treatment resulted in a temporary increased expression of interferon (IFN)-stimulating genes and it worsened the recovery of CD4(+) T cells in the blood. Our findings confirm recent results observed in asymptomatic HIV-infected patients and suggest that CQ does not provide an obvious benefit in the absence of antiretroviral therapy.

Antibodies to gp120 and PD-1 expression on virus-specific CD8+ T cells in protection from simian AIDS.

We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4(+) and CD8(+) T-cell responses but differed in the level of antibody responses to the gp120 envelope protein. All macaques were primed with DNA plasmids expressing SIV gag, pol, env, and Retanef genes and were boosted with recombinant modified vaccinia Ankara virus (MVA) expressing the same genes, either once (1 × MVA) or twice (2 × MVA), or were boosted once with MVA followed by a single boost with replication-competent adenovirus (Ad) type 5 host range mutant (Ad5 h) expressing SIV gag and nef genes but not Retanef or env (1 × MVA/Ad5). While two of the vaccine regimens (1 × MVA and 1 × MVA/Ad5) protected from high levels of SIV replication only during the acute phase of infection, the 2 × MVA regimen, with the highest anti-SIV gp120 titers, protected during the acute phase and transiently during the chronic phase of infection. Mamu-A*01 macaques of this third group exhibited persistent Gag CD8(+)CM9(+) effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen. The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8(+) T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8(+) T-cell responses.

Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.

We used the simian immunodeficiency virus mac251 (SIV(mac251)) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 in alum, and we challenged them with SIV(mac251) at either a single high dose or at two repeated low-dose exposures to a 10-fold-lower dose. Infection was neither prevented nor modified following a single high-dose challenge of the immunized macaques. However, two exposures to a 10-fold-lower dose resulted in protection from SIV(mac251) acquisition in 3 out of 12 macaques. The remaining animals that were infected had a modulated pathogenesis, significant downregulation of interferon responsive genes, and upregulation of genes involved in B- and T-cell responses. Thus, the choice of the experimental model greatly influences the vaccine efficacy of vaccines for human immunodeficiency virus (HIV).

Fatal pancreatitis in simian immunodeficiency virus SIV(mac251)-infected macaques treated with 2',3'-dideoxyinosine and stavudine following cytotoxic-T-lymphocyte-associated antigen 4 and indoleamine 2,3-dioxygenase blockade.

Human immunodeficiency virus (HIV) infection is associated with immune activation, CD4⁺-T-cell loss, and a progressive decline of immune functions. Antiretroviral therapy (ART) only partially reverses HIV-associated immune dysfunction, suggesting that approaches that target immune activation and improve virus-specific immune responses may be needed. We performed a preclinical study in rhesus macaques infected with the pathogenic simian immunodeficiency virus SIV(mac251) and treated with ART. We tested whether vaccination administered together with cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) blockade and treatment with the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyl-D-tryptophan (D-1mT), decreased immune activation and improved vaccine efficacy. The treatment did not augment vaccine immunogenicity; rather, it dramatically increased ART-related toxicity, causing all treated animals to succumb to acute pancreatitis and hyperglycemic coma. The onset of fulminant diabetes was associated with severe lymphocyte infiltration of the pancreas and complete loss of the islets of Langerhans. Thus, caution should be used when considering approaches aimed at targeting immune activation during ART.

Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA.

The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV. We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV(mac251.) HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.

Smallpox vaccine safety is dependent on T cells and not B cells.

The licensed smallpox vaccine, ACAM2000, is a cell culture derivative of Dryvax. Both ACAM2000 and Dryvax are administered by skin scarification and can cause progressive vaccinia, with skin lesions that disseminate to distal sites. We have investigated the immunologic basis of the containment of vaccinia in the skin with the goal to identify safer vaccines for smallpox. Macaques were depleted systemically of T or B cells and vaccinated with either Dryvax or an attenuated vaccinia vaccine, LC16m8. B cell depletion did not affect the size of skin lesions induced by either vaccine. However, while depletion of both CD4(+) and CD8(+) T cells had no adverse effects on LC16m8-vaccinated animals, it caused progressive vaccinia in macaques immunized with Dryvax. As both Dryvax and LC16m8 vaccines protect healthy macaques from a lethal monkeypox intravenous challenge, our data identify LC16m8 as a safer and effective alternative to ACAM2000 and Dryvax vaccines for immunocompromised individuals.

Gp96 SIV Ig immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa.

The ER-resident chaperone gp96, when released by cell lysis, induces an immunogenic chemokine signature and causes innate immune activation of DC and NK cells. Here we show that intraperitoneal immunization with a genetically engineered, secreted form of gp96, gp96-Ig chaperoning SIV antigens, induces high levels of antigen specific CD8 CTL in the rectal and vaginal mucosa of Rhesus macaques. The frequency of SIV Gag- and SIV Tat-tetramer positive CD8 CTL in the intestinal mucosa reached 30-50% after the third immunization. Tetramer positive CD8 CTL expressed appropriate functional (granzyme B) and migration markers (CD103). The polyepitope specificity of the mucosal CD8 and CD4 response is evident from a strong, multifunctional cytokine response upon stimulation with peptides covering the gag, tat and env proteins. Induction of powerful mucosal effector CD8 CTL responses by cell-based gp96(SIV)-Ig immunization may provide a pathway to the development of safe and effective SIV/HIV vaccines.

Requirement of the human T-cell leukemia virus p12 and p30 products for infectivity of human dendritic cells and macaques but not rabbits.

The identification of the genes necessary for human T-cell leukemia virus (HTLV-1) persistence in humans may provide targets for therapeutic approaches. We demonstrate that ablation of the HTLV-1 genes encoding p12, p30, or the HBZ protein, does not affect viral infectivity in rabbits and in this species, only the absence of HBZ is associated with a consistent reduction in virus levels. We observed reversion of the HTLV-1 mutants to the HTLV-1 wild-type genotype in none of the inoculated rabbits. In contrast, in macaques, the absence of HBZ was associated with reversion of the mutant virus to the wild-type genotype in 3 of the 4 animals within weeks from infection. Similarly, reversion to the wild type was observed in 2 of the 4 macaque inoculated with the p30 mutant. The 4 macaques exposed to the p12 knock remained seronegative, and only 2 animals were positive at a single time point for viral DNA in tissues. Interestingly, we found that the p12 and the p30 mutants were also severely impaired in their ability to replicate in human dendritic cells. These data suggest that infection of dendritic cells may be required for the establishment and maintenance of HTLV-1 infection in primate species.

Reduced protection from simian immunodeficiency virus SIVmac251 infection afforded by memory CD8+ T cells induced by vaccination during CD4+ T-cell deficiency.

Adaptive CD4(+) and CD8(+) T-cell responses have been associated with control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication. Here, we have designed a study with Indian rhesus macaques to more directly assess the role of CD8 SIV-specific responses in control of viral replication. Macaques were immunized with a DNA prime-modified vaccinia virus Ankara (MVA)-SIV boost regimen under normal conditions or under conditions of antibody-induced CD4(+) T-cell deficiency. Depletion of CD4(+) cells was performed in the immunized macaques at the peak of SIV-specific CD4(+) T-cell responses following the DNA prime dose. A group of naïve macaques was also treated with the anti-CD4 depleting antibody as a control, and an additional group of macaques immunized under normal conditions was depleted of CD8(+) T cells prior to challenge exposure to SIV(mac251). Analysis of the quality and quantity of vaccine-induced CD8(+) T cells demonstrated that SIV-specific CD8(+) T cells generated under conditions of CD4(+) T-cell deficiency expressed low levels of Bcl-2 and interleukin-2 (IL-2), and plasma virus levels increased over time. Depletion of CD8(+) T cells prior to challenge exposure abrogated vaccine-induced protection as previously shown. These data support the notion that adaptive CD4(+) T cells are critical for the generation of effective CD8(+) T-cell responses to SIV that, in turn, contribute to protection from AIDS. Importantly, they also suggest that long-term protection from disease will be afforded only by T-cell vaccines for HIV that provide a balanced induction of CD4(+) and CD8(+) T-cell responses and protect against early depletion of CD4(+) T cells postinfection.

Cannabinoids enhance gastric X/A-like cells activity.

It has been reported that cannabinoids may cause overeating in humans and in laboratory animals. Although, endogenous cannabinoids and their receptors (CB1) have been found in the hypothalamus, and recently also in gastrointestinal tract, the precise mechanism of appetite control by cannabinoids remains unknown. Recently, ghrelin--a hormone secreted mainly from the stomach X/A-like cells was proposed to be an appetite stimulating agent. The aim of this study was the evaluation of the influence of a single ip injection of a stable analogue of endogenous cannabinoid--anandamide, R-(+)-methanandamide (2.5 mg/kg) and CP 55,940 (0.25 mg/kg), an exogenous agonist of CB1 receptors, on ghrelin plasma concentration and on ghrelin immunoreactivity in the gastric mucosa of male Wistar rats. Four hours after a single injection of both cannabinoids or vehicle, the animals were anaesthetized and blood was taken from the abdominal aorta to determinate plasma ghrelin concentration by RIA. Subsequently, the animals underwent resection of distal part of stomach. Immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antibodies against ghrelin was performed. The intensity of ghrelin immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. The attenuation of ghrelin-immunoreactivity of gastric mucosa, after a single injection of R-(+)-methanandamide and CP 55,940 was accompanied by a significant increase of ghrelin plasma concentration. These results indicate that stimulation of appetite exerted by cannabinoids may be connected with an increase of ghrelin secretion from gastric X/A-like cells.