Sample-size dependence of validation parameters in linear regression models and in QSAR.

The dependence of statistical validation parameters was investigated on the size of the sample taken in fit of multivariate linear curves. We observed that R2 and related internal parameters were misleading as they overestimated the goodness-of-fit of models at small sample size. Cross-validation metrics showed correct trends. It was possible to scale the leave-one-out and the leave-many-out results close to identical by correcting the degrees of freedom of the models. y and x-randomized validation parameters were calculated and the methods provided close to identical results. We suggest to use the simplest methods in both cases. The external parameters followed correct trends with respect to the sample size, but their sensitivity differed. We plotted the Roy-Ojha metrics in 2D and we coloured them with respect to other external parameters to provide an easy classification of models. The rank correlations were calculated between the performance parameters. Up to a sample size, goodness-of-fit and robustness were distinguishable, but above a certain sample size, the parameters were redundant. The external-internal pairs were weakly correlated. Our data show that all the three aspects of validation are necessary at small sample sizes, but the internal check of robustness is not informative above a given sample size.

Mitochondrial protective effects of PARP-inhibition in hypertension-induced myocardial remodeling and in stressed cardiomyocytes.

AIMS: During oxidative stress mitochondria become the main source of endogenous reactive oxygen species (ROS) production. In the present study, we aimed to clarify the effects of pharmacological PARP-1 inhibition on mitochondrial function and quality control processes. MAIN METHODS: L-2286, a quinazoline-derivative PARP inhibitor, protects against cardiovascular remodeling and heart failure by favorable modulation of signaling routes. We examined the effects of PARP-1 inhibition on mitochondrial quality control processes and function in vivo and in vitro. Spontaneously hypertensive rats (SHRs) were treated with L-2286 or placebo. In the in vitro model, 150 µM H2O2 stress was applied on neonatal rat cardiomyocytes (NRCM). KEY FINDINGS: PARP-inhibition prevented the development of left ventricular hypertrophy in SHRs. The interfibrillar mitochondrial network were less fragmented, the average mitochondrial size was bigger and showed higher cristae density compared to untreated SHRs. Dynamin related protein 1 (Drp1) translocation and therefore the fission of mitochondria was inhibited by L-2286 treatment. Moreover, L-2286 treatment increased the amount of fusion proteins (Opa1, Mfn2), thus preserving structural stability. PARP-inhibition also preserved the mitochondrial genome integrity. In addition, the mitochondrial biogenesis was also enhanced due to L-2286 treatment, leading to an overall increase in the ATP production and improvement in survival of stressed cells. SIGNIFICANCE: Our results suggest that the modulation of mitochondrial dynamics and biogenesis can be a promising therapeutical target in hypertension-induced myocardial remodeling and heart failure.

Combined dual energy and iterative metal artefact reduction for PET/CT in head and neck cancer.

Metal artefacts in PET/CT images hamper diagnostic accuracy in head and neck cancer (HNC). The aim of this study is to characterise the clinical effects of metal artefacts on PET/CT in HNC and to inform decision-making concerning implementation of MAR techniques. We study a combined dual energy CT and inpainting-based metal artefact reduction (DECT-I-MAR) technique for PET/CT in three settings: (A) A dental phantom with a removable amalgam-filled tooth to evaluate the PET error in comparison to a known reference. (B) PET-positive patients with metallic implants to demonstrate the relationship between CT metal artefacts and PET error. (C) Metabolic tumour volumes delineated in PET-positive patients with metal implants to evaluate the clinical impact. In (A) DECT-I-MAR reduced the PET error significantly. In (B) we demonstrate an increasing PET error with increasing CT artefact severity in patients. In (C) it is shown that the presence of artefacts in the same axial slices as the tumour significantly decreases biomarker stability and increase delineation variability. This work shows the practical feasibility of DECT-I-MAR-based PET/CT imaging, and indicates a positive clinical impact of using the technique routinely for HNC patients. The impact of CT artefacts on PET is considerable, especially in workflows where quantitative PET biomarkers and tumour volumes are used. In such cases, and for patients with tumours in proximity of metals, we recommend that a MAR technique for PET/CT is employed.

That dog won't fit: body size awareness in dogs.

With very few exceptions, no coherent model of representing the self exists for nonhuman species. According to our hypothesis, understanding of the Self as an object' can also be found in a wide range of animals including the dog, a fast-moving terrestrial predator/scavenger, with highly developed senses and complex cognitive capacity. We tested companion dogs in three experiments in which they faced three different variations of the same physical challenge: passing through an opening in a wall. We predicted that if dogs are capable of representing their own body size, they will react differently when faced with adequate or too small openings. We found that dogs started to move towards and approached the too small openings with significantly longer latencies than the suitable ones; and upon reaching it, they did not try to get through the too small openings. In another experiment, the medium-size (still large enough) opening was approached with latencies that fell between the latencies measured in the cases of the very large or the too small openings. Having discussed the potential underlying mechanisms, we concluded that our results convincingly assume that dogs can represent their own body size in novel contexts.

Effectiveness of the Gerundium Youth Educating Program in Hungary.

The acceptance of brain death and the legitimation of organ transplantation is very much dependent on the general knowledge of the society. In Hungary, the legislation of brain death is based on presumed consent. There is no structural education about the topic so far. AIM: The role of the Gerundium program is to educate high school students about the importance of transplantation and the meaning of brain death. The goal of this study was to evaluate the effectiveness of the Gerundium contemporary educational program in a pilot study. METHOD: The education was held by medical students who successfully completed a preparatory elective course consisting of relevant information in the topic. Medical students used simple language during the 45-minute presentations. Two tests with simple but representative questions created by experts were completed by high school students: one directly before contemporary education and another 5 to 6 weeks after the lecture. RESULTS: A total of 147 tests were completed: 78 before and 69 after the presentation in the city of Debrecen and 294 before the lecture in the city of Gyor. In Debrecen, the overall correct answers increased by 6.05% (P < .05; before vs after). The results show that the knowledge transfer is highly effective in this manner and the students know significantly more weeks after the lectures. CONCLUSION: There is much to do to broadly inform society about transplantation and brain death, but we will continue to increase the number of students and measure the dynamic change of the students' knowledge.

Surgical Treatment of Hyperparathyroidism After Kidney Transplant.

Chronic renal impairment is often associated with complex bone disorders. Improvement of secondary hyperparathyroidism (HPT) is expected after kidney transplant (KT) if the glomerular filtration rate is normalized. PATIENTS AND METHODS: There were 888 KTs performed between 1996 and 2017 at our department. A total of 558 general patients have been operated on for HPT during the same period. The 2 populations had a common part: out of the 558, a total of 69 (12.4%) were in end-stage renal failure when operated on because of secondary HPT. That also means that 7.8% of all KTs were associated with HPT. Retrospective, single-center analysis was performed using the patients' medical records. The aim of our study was to analyze the results of parathyroidectomies after KT. RESULTS: Parathyroid surgery was performed on 19 patients (2.14%) because of HPT after KT. The applied surgical technique was total parathyroidectomy with autotransplant in 6 cases, subtotal parathyroidectomy in 3 cases, and selective parathyroidectomy in 10 cases. In all cases, histology revealed benign disease. Complications were observed in 10 cases (52%); there were 6 cases of postoperative hypocalcaemia (31.58%), 1 case of transient laryngeal recurrent nerve paresis (5.26%), and 6 cases of recurrent HPT (31.58%). SUMMARY: The first step of HPT management is calcimimetic drug treatment. It is essential to prevent possible complications with regular laboratory monitoring. If the proper conservative therapy is refractory or severe in complications, surgery should be chosen. If the patient is already waiting for a KT, it is worth performing the parathyroid surgery before KT. Close collaboration with endocrinologists and nephrologists is needed to achieve successful therapy.

Autosomal Dominant Polycystic Kidney Disease Transplant Recipients After Kidney Transplantation: A Single-center Experience.

Kidney transplantation is indicated for end-stage renal disease. Autosomal dominant polycystic kidney disease (ADPKD) causes structural degeneration of the kidney and eventually becomes end-stage renal disease. ADPKD patients usually have several renal and nonrenal complications. We analyzed our kidney transplantation activities between 1991 and 2010 regarding ADPKD. We followed up with patients to December 31, 2016. Data were collected as patient and graft survival rates, the prevalence of polycystic manifestation of the gastrointestinal tract and other organs, and the attendance of urinary tract infection. Among the 734 kidney transplantations, 10.9% (n = 80) had an ADPKD. Four patients (5%) had diverticulum perforation. The prevalence of post-transplantation urinary tract infection was higher in ADPKD patients (55.9%) compared to non-ADPKD patients (44.1%). The 1-, 3-, and 5-year overall survival rates in ADPKD recipients versus non-ADPKD patients are 77.5%, 70.0%, and 67.5% versus 86.4%, 83.0%, and 80.1%, respectively. Patients with ADPKD were transplanted at an elder age compared to others (median: 47.5 years vs. 39.9 years). Female patients had longer graft survival times than males. ADPKD implies multiple cystic degeneration of the kidneys; however, it can cause structural degeneration in other organs. It is typical for ADPKD patients to have an acute abdominal-like syndrome. Immunosuppressive drugs can hide the clinical picture, which makes early diagnosis difficult.

Sebum lipids influence macrophage polarization and activation.

BACKGROUND: As lipids are known to regulate macrophage functions, it is reasonable to suppose that a sebocyte-macrophage axis mediated by sebum lipids may exist. OBJECTIVES: To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids. METHODS: Oil Red O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets. Human peripheral blood monocytes were differentiated in the presence of either supernatant from human SZ95 sebocytes or major sebum lipid components and activated with Propionibacterium acnes. Macrophage surface markers and their capacity to uptake fluorescein isothiocyanate-conjugated P. acnes were detected by fluorescence-activated cell sorting measurements. Cytokine protein levels were evaluated by enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: Sebaceous gland-rich skin had an increased dermal lipid content vs. sebaceous gland-poor skin to which all the tested sebum component lipids could contribute by penetrating the dermoepidermal barrier. Of the lipids, oleic acid and linoleic acid promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti-inflammatory effect in P. acnes-activated macrophages, inhibiting the secretion of interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α. Squalene, palmitic acid, stearic acid and oleic acid augmented the secretion of IL-1ß, even in the absence of P. acnes, whereas oleic acid had a selective effect of inducing IL-1ß but downregulating IL-6 and TNF-α secretion. CONCLUSIONS: Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathological and therapeutic relevance.

A Single-center Experience of Allograft Nephrectomies Following Kidney Transplantation.

INTRODUCTION: Approximately 10% of renal allografts fail during the first year after kidney transplantation (KT) and 3%-5% thereafter yearly. The indication and timing of allograft nephrectomy (AN) is still uncertain in some cases. The aim of this study was to reveal the ratio, etiology, and complications of AN at our center. MATERIAL AND METHODS: This is a retrospective study of all patients who underwent KT at our center between January 1, 2004 and December 31, 2014. We analysed the frequency, indications, timing, and complications of ANs. Also early and late ANs were compared. RESULTS: From 417 renal transplantations 49 ANs were performed (11.7%). The most frequent indications were chronic allograft nephropathy (25; 51%), arterial blood supply complications, like arterial thrombosis and stenosis (7; 15%), treatment-resistant acute rejection (3; 6%), and nonreparable ureter complications (3; 6%). The average time of AN since KT was 28 months. ANs were performed as an urgent setting in 16 (33%) cases, whereas it was elective in 33 cases (67%). The AN was executed within 30 days (early) in 11 (22%) cases, and thereafter (late) in 38 (78%) cases. The main indication for early AN was renal artery thrombosis (4; 37%) and chronic allograft nephropathy (25; 66%) for late AN. Surgical complications occurred in 10 cases (20; 4%). The most common was hematoma. CONCLUSION: The majority of the ANs were elective and late (more than 30 days; average time, 47 months). Leading indication was chronic allograft nephrectomy. Early ANs were urgent and life-saving in all cases.

Surgical Complications Following Kidney Transplantations: A Single-Center Study in Hungary.

Surgical complications (SCs) are still high potential causes of graft loss. The incidence has a huge amount of variations depending on many factors. Our aim was to study the postoperative technical complications following kidney transplantations (KTs) during a 5-year period between 2011 and 2015. In the observed time frame there were 47 SCs occurring in 32 (19.4%) patients of 165 KTs. Every complication was classified into 3 groups: vascular (11; 6.6%), urologic (16; 9.7%), and any others (20; 12.1%). The most common postoperative SCs in our center were hemorrhage (14; 8.5%), urinary leakage (12; 7.2%), and renal artery stenosis (6; 3.6%). Twenty-seven patients, 84% of those having had a SC, needed an intervention, mainly a surgical correction (28; 62%). Half of these interventions (21; 51%) were performed due to urologic reasons. As possible predicting factors, we studied the type of arterial and ureter anastomosis in relation to onset of vascular and urologic complications. There was no significant correlation. The same was true for any donor and/or recipient demographic parameters. However, the presence of SCs impaired both patient and graft survival. The cumulative 6-month, 1-, 3-, and 5-year patient survival rates were 97% versus 99%, 93% versus 99%, 84% versus 97%, and 84% versus 97% for patients with/without (w/wo) a SC, respectively (P = .028). The cumulative 6-month, 1-, 3-, and 5-year graft survival rates were 81% versus 96%, 77% versus 94%, 68% versus 86%, and 54% versus 86% for the same 2 groups, respectively (P = .003).

Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms.

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings.

Distinct effects of folate pathway genes MTHFR and MTHFD1L on ruminative response style: a potential risk mechanism for depression.

Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309). Post hoc analysis investigated whether the association could be replicated in each of the two samples, and the relationship between folate pathway genes, rumination, lifetime depression and Brief Symptom Inventory depression score. Despite its functional effect on folate metabolism, the MTHFR rs1801133 showed no effect on rumination. However, the A allele of MTHFD1L rs11754661 was significantly associated with greater rumination, and this effect was replicated in both the Budapest and Manchester samples. In addition, rumination completely mediated the effects of MTHFD1L rs11754661 on depression phenotypes. These findings suggest that the MTHFD1L gene, and thus the C1-THF synthase enzyme of the folate pathway localized in mitochondria, has an important effect on the pathophysiology of depression through rumination, and maybe via this cognitive intermediate phenotype on other mental and physical disorders. Further research should unravel whether the reversible metabolic effect of MTHFD1L is responsible for increased rumination or other long-term effects on brain development.

Gerundium: A Comprehensive Public Educational Program on Organ Donation and Transplantation and Civil Law in Hungary.

BACKGROUND: Organ transplantation has become an organized, routine, widely used method in the treatment of several end-stage diseases. Kidney transplantation means the best life-quality and longest life expectancy for patients with end-stage renal diseases. Transplantation is the only available long-term medical treatment for patients with end-stage liver, heart, and lung diseases. Despite the number of transplantations increasing worldwide, the needs of the waiting lists remain below expectations. METHODS: One of the few methods to increase the number of transplantations is public education. In cooperation with the University of Debrecen Institute for Surgery Department of Transplantation, the Hungarian National Blood Transfusion Service Organ Coordination Office, and the Local Committee Debrecen of Hungarian Medical Students' International Relations Committee (HuMSIRC), the Gerundium, a new educational program, has been established to serve this target. Gerundium is a special program designed especially for youth education. Peer education means that age-related medical student volunteers educate their peers during interactive unofficial sessions. RESULTS: Volunteers were trained during specially designed training. Medical students were honored by HuMSIRC, depending on their activity on the basis of their own regulations. Uniform slides and brochures to share were designed. Every Hungarian secondary school was informed. The Local Committee Budapest of HuMSIRC also joined the program, which helps to expand our activity throughout Hungary. The aim of the program is public education to help disperse disapproval, if presented. CONCLUSIONS: As a multiple effect, our program promotes medical students to have better skills in the field of transplantation, presentation, and communication skills. Our program is a voluntary program with strong professional support and is free of charge for the community.

Results of Expanded-Criteria Donor Kidneys: A Single-Center Experience in Hungary.

BACKGROUND: To ease organ shortage, many transplant centers accept kidneys from expanded-criteria donors (ECDs). Our aim was to analyze the results of ECD grafts in our center. METHODS: Data on cadaveric donors were retrospectively analyzed between January 2011 and September 2014. Definition of ECD was: (1) donor age ≥60 years, (2) donor age 50 to 59 years, and (3) the presence of 2 among the following criteria: hypertension, serum creatinine >1.5 mg/dL, or death from cerebrovascular accident. Standard-criteria donors (SCDs) were those who did not meet the criteria for an ECD. RESULTS: During the observation period, 215 cadaveric donors were reported within our region, and 14 kidneys were offered to our center from Eurotransplant. Ninety-one (40%) among the reported donors were ECDs and 123 (54%) were SCDs. The rates of delayed graft function (DGF) and acute rejection (ARE) were not influenced by transplantation of an ECD graft. The cumulative patient and graft survival rates for ECDs were comparable with those of patients who received an optimal graft. CONCLUSIONS: ECD grafts can be transplanted safely, without the increased risk of DGF, ARE, and inferior patient and graft survival, in the case of careful patient allocation, and with the use of induction therapy.

Serum C-reactive protein and white blood cell level as markers of successful percutaneous drainage of acute sterile peripancreatic fluid collection.

BACKGROUND: Percutaneous drainage is not a widely used therapeutic method recently for evacuating peripancreatic sterile fluid collections in patients with severe acute pancreatitis.However, many clinical studies have proved its positive effects. AIM: We tested the changes in serum laboratory parameters:C-reactive protein (CRP), complement factor 3-4 (C 3-4),tumor necrosis factor a (TNF-a), amylase, lipase and white blood cell (WBC) count in patients treated by percutaneous drainage. PATIENTS AND METHODS: 10 patients with severe acute pancreatitis with peripancreatic fluid collection were monitored.Laboratory parameters and the amount of drained fluid were measured on the 1st, 5th and 10th day. Statistical analysis was performed by using Statistica for Windows (Version 7.0)software. P values less than 0.05 were considered statistically significant. RESULTS: We found significant positive correlation between the CRP and WBC serum level and volumes of the drained fluid. We used these parameters as markers of successful percutaneous drainage in case of patients with severe acute pancreatitis complicated with sterile peripancreatic fluid.There was no significant change in the levels of C 3-4,tumor necrosis factor-Î+-, amylase and lipase. CONCLUSIONS: Monitoring of serum CRP and WBC levels maybe recommended for follow up after percutaneous drainage of peripancreatic fluid. ABBREVIATIONS: CRP: C-reactive Protein TNFÎ+-: Tumour Necrosis Factor a, C3-4: Complement 3-4 WBC: White Blood Cell CT: Computed Tomography.

Vitiligo: characterization of melanocytes in repigmented skin after punch grafting.

BACKGROUND: Punch grafting is a surgical technique mainly applied in therapy-resistant, stable and circumscribed vitiligo. OBJECTIVE: (i) To characterize in detail the features of the repigmented skin among punch grafts; and (ii) to correlate the ex vivo results with clinical data and punch grafting outcome. METHODS: We evaluated by immunohistochemistry and image analysis the expression of a panel of specific melanocyte markers including HMB45, MITF, c-kit, MART-1 and TRP1, the proliferation marker Ki67 and the cell-cell adhesion molecule E-cadherin in tissue samples collected from nine patients after punch grafting. RESULTS: Cells positive for MITF, c-kit, MART-1 and TRP1 were detected in the repigmented skin of all biopsies, whereas no reactivity was observed for HMB45. Melanocytes were identified along the entire length of the sections, and their mature state was assessed by the immuno-reactivity for the differentiation marker MART-1, the absence of cells positively stained for Ki67 and by the co-expression of c-kit and TRP1, a marker of a differentiated and pigmented state. Clinically, smaller punch grafts aimed at repigmenting lesional areas on the face gave the faster clinical results with no side-effects. Patients subjected to bigger punch grafts on the knee exhibited a longer repigmentation time and presented cobble stoning. CONCLUSION: Our results suggest that the repigmentation observed in the areas between the grafts is due to the activation of the melanocytes located in the donor sites. These cells start to horizontally migrate towards the lesional skin thanks to successively the enlargement of intercellular spaces in relation to a decrease of E-cadherin reactivity and the up-modulation of pro-melanogenic mediators. Production and transfer of melanin in the surrounding keratinocytes and their persistence were assessed by the reactivity for MITF, c-kit, MART-1 and TRP1 but not for the pre-melanosome marker (HMB45).

Three-year longitudinal clinical trial of arterial function assessed by a oscillometric non-invasive method in comparison with carotid sclerosis and transferrin kidney-transplanted patients.

Chronic kidney disease remains one of the main risk factors of cardiovascular disease. However, patients with kidney transplantation have better life expectancy and better quality of life compared with patients on dialysis. In patients with a well-functioning graft, the main cause of death is cardiovascular in origin. Metabolic pathways have complex effects on arterial function that can be monitored by conventional ultrasonography and with the assessment of arterial stiffness by oscillometric non-invasive technique. Forty-one primer cadaver kidney-transplanted patient were involved in a 3-year longitudinal clinical trial (21 female, 20 male; average age, 40.16 ± 12.56 years). Arterial stiffness parameters referring to rigidity of the arterial wall (pulse wave velocity [PWV], augmentation index, and pulse pressure) were investigated. Correlation between stiffness, and laboratory parameters (serum creatinine, urea, hemoglobin, albumin, cholesterine, triglycerides, transferrin, uric acid, glomerular filtration rate, and C-reactive protein) were analyzed. A non-invasive oscillometric method--Tensiomed Arteriograph--was applied to assess the arterial stiffness parameters. Statistical analysis was performed with the use of Statistica for Windows, version 8.0. A value of P < .05 was considered statistically significant for all statistical tests. We found a positive correlation between PWV and left ventricular wall thickness and a negative correlation between PWV and ejection fraction. We also found a positive significant correlation between serum level of transferrin and PWV. There was simultaneous significant progression concerning PWV and carotid artery sclerosis in a 3-year follow-up. There was no fatal cardiovascular event during the study period among our patients. All of our patients involved in this study are still alive. Our findings suggest that arterial stiffness monitoring is a reliable method to assess global cardiovascular risk among kidney-transplanted patients. The oscillometric method is convenient, fast, painless technique to monitor arterial function, which, in the case of pathological findings, proposes more frequent cardiovascular control.

Leptin promotes a proinflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytes.

BACKGROUND: Leptin, the adipocyte-secreted hormone that regulates weight, is known to link lipid metabolism with inflammation in various cell types. However, its role in human sebocytes has not yet been investigated. OBJECTIVES: The purpose of this study was to investigate the effects of leptin in human sebaceous gland biology. METHODS: Expression of the long form of the leptin receptor (Ob-Rb) was detected by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunochemistry. Lipid analysis was by high-performance thin-layer chromatography, gas chromatography-mass spectrometry and time-of-flight mass spectrometer mass detection. Lipid bodies were visualized by BODIPY staining using fluorescent microscopy and measured by flow cytometry. Interleukin (IL)-6 and IL-8 mRNA levels were assessed by real-time qRT-PCR and their release was evaluated by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 and 5-lipooxygenase (LOX) protein expression and phosphorylation of p65 and signal transducer and activator of transcription (STAT)-3 were determined by Western blot analysis. RESULTS: Expression of Ob-Rb was detected in human sebaceous glands and in cultured human SZ95 sebocytes. The treatment of SZ95 sebocytes with leptin led to enlarged intracellular lipid bodies, increased ratios of unsaturated/saturated fatty acids and decreased vitamin E levels. Further supporting a proinflammatory role, leptin induced COX-2 and 5-LOX expression in SZ95 sebocytes and augmented the production of IL-6 and IL-8 cytokines. On leptin treatment, the STAT-3 and nuclear factor-κB pathways were activated, indicating that these known leptin signalling pathways are active in human sebocytes. CONCLUSIONS: Our findings suggest that leptin signalling may be involved in the proinflammatory regulation of sebaceous lipid metabolism and the induction of inflammatory enzymes and cytokines.