Rare Case of Tularemia With Preauricular Lymphadenopathy and Conjunctivitis in a 27-Year-Old Male Patient in Germany.

Tularemia is a rare disease but shows an approximately 10-fold increase in reported cases over the last 15 years in Germany. Clinical symptoms of acute tularemia infection are various, which often delays diagnosis. This case report gives an overview of the clinical manifestations of acute tularemia and shows the importance of interdisciplinary work to shorten the time from the onset of symptoms to effective treatment in infection with Francisella tularensis. Since some cases of tularemia are life-threatening, early diagnosis is vital. This case report serves as a reminder that rare diseases need to be considered in cervical lymphadenopathy.

Sensor-based intervention to enhance movement control of the spine in low back pain: Protocol for a quasi-randomized controlled trial.

Introduction: Chronic low back pain is a common condition that imposes an enormous burden on individuals and society. Physical exercise with education is the most effective treatment, but generally results in small, albeit significant improvements. However, which type of exercise is most effective remains unknown. Core stability training is often used to improve muscle strength and spinal stability in these patients. The majority of the core stability exercises mentioned in intervention studies involve no spinal movements (static motor control exercises). It is questionable if these exercises would improve controlled movements of the spine. Sensor-based exergames controlled with spinal movements could help improve movement control of the spine. The primary aim of this study is to compare the effects of such sensor-based exergames to static motor control exercises on spinal movement control. Methods and analysis: In this quasi-randomized controlled trial, 60 patients with chronic low back pain who are already enrolled in a multidisciplinary rehabilitation programme will be recruited. Patients will be randomly allocated into one of two groups: the Sensor-Based Movement Control group (n = 30) or the Static Motor Control group (n = 30). Both groups will receive 8 weeks of two supervised therapy sessions and four home exercises per week in addition to the rehabilitation programme. At baseline (week 1) and after the intervention (week 10), movement control of the spine will be assessed using a tracking task and clinical movement control test battery. Questionnaires on pain, disability, fear avoidance and quality of life will be taken at baseline, after intervention and at 6- and 12 months follow-up. Repeated measures ANOVAs will be used to evaluate if a significant Group x Time interaction effect exists for the movement control evaluations. Discussion: Sensor-based spinal controlled exergames are a novel way to train spinal movement control using meaningful and engaging feedback. The results of this study will inform clinicians and researchers on the efficacy of movement control training for patients with low back pain. Ethics and dissemination: Ethical approval for this study protocol was obtained from the METC Brabant (protocol number NL76811.028.21). Trial registration: Open Science Framework Registries (https://osf.io/v3mw9/), registration number: 10.17605/OSF.IO/V3MW9, registered on 1 September 2021.

Training potential of visual feedback to improve dynamic postural stability.

BACKGROUND: Deficits in single-limb dynamic postural stability are predictive for reinjuries of the lower extremities, which are very common in sports. The use of force plates has become increasingly common to measure dynamic postural stability. Visual feedback on force-plate based stability outcomes have been shown to improve performance during static tasks. A similar effect might occur in dynamic tasks. Since dynamic tasks are generally more specific for performance during sport, this could have important training implications. RESEARCH QUESTION: What is the effect of visual feedback on postural stability outcomes during a dynamic stability task? METHODS: Twenty-four healthy participants participated in this study. During measurements, subjects were standing on one leg while mediolateral position-controlled platform perturbations were used to evoke and measure balance responses. All participants were tested under three conditions: with visual Time-to-Stability (TTS) feedback, with visual Center of Pressure speed (COPs) feedback and without visual feedback. TTS and COPs outcomes were calculated over a 5-second time window after each perturbation and were compared between conditions. RESULTS: Visual feedback resulted in significantly better stability outcomes during the dynamic stability task. TTS feedback resulted in a task-specific feedback learning effect, as it resulted in a gradual improvement of TTS scores (from 1.09 s to 0.68 s; -38%) in absence of a significant change in COPs. COPs feedback resulted in a non-specific attention effect, directly improving COPs (without feedback 5.26 cm/s with feedback 4.95 cm/s; -6%) and TTS scores (without feedback 1.47 s with feedback 0.99 s; -39%) in absence of an apparent further improvement over time. SIGNIFICANCE: The ability to improve performance of dynamic stability tasks when visual feedback is added could have substantial impact for rehabilitation. Possibly, the use of visual feedback during stability training could improve the effectiveness of postural stability training.

Indocyanine Green Fluorescence Angiography Can Guide Intraoperative Localization During Parathyroid Surgery.

BACKGROUND AND AIMS: Intraoperative localization of pathologic parathyroid glands is of major importance for the hyperparathyroidism treatment. Based on the small size and the anatomic variability, the localization can be very challenging. The current practice is to compare preoperative ultrasonography with Technetium-99m sestamibi scintigraphy (MIBI) and plan the resection accordingly. In this study, we implemented indocyanine green angiography for the intraoperative localization of parathyroid glands. MATERIALS AND METHODS: This is a retrospective analysis of 37 patients with primary, secondary, or tertiary hyperparathyroidism who were operated using indocyanine green angiography for the intraoperative localization of pathological parathyroid glands. An indocyanine green solution of 2.5 mg was were intravenously administered for parathyroid gland visualization. Different fluorescence scores were correlated with changes in postoperative parathyroid hormone levels. RESULTS: Patients were divided into two groups depending on the presence of uniglandular or multiglandular disease. Sixty-four lesions were resected, and the final histopathologic analysis confirmed the parathyroid origin in 62 of them (96.8%). None of the patients with uniglandular disease developed postoperative hypoparathyroidism, whereas three patients in the multiglandular group developed temporary hypoparathyroidism symptoms. Indocyanine green imaging had higher sensitivity for the intraoperative detection of parathyroid glands compared with ultrasonography and MIBI (p < 0.001). CONCLUSION: Indocyanine green angiography indicated high sensitivity for the intraoperative identification of pathologic parathyroid glands leading to a resection rate of 95.16%. The modality was useful, especially in cases of revisional surgery or ectopic parathyroid glands. Randomized trials have already proven the value of indocyanine green imaging in predicting postoperative hypocalcemia. Our results support the regular use of this method during parathyroid surgery.

[Necrotizing fasciitis in the head and neck region-three case reports and a review of the literature]. / Nekrotisierende Fasziitis der Kopf-Hals-Region ­ 3 Fallberichte und Literaturübersicht.

Necrotizing fasciitis (NF) is a life-threatening, usually bacterial, soft tissue infection that rarely affects the head and neck region. Rapid progression and systemic illness are typical for the disease and complicate diagnosis. Immediate surgical and antimicrobial therapy is required. Three cases of cervicofacial NF are presented in this case report. All patients showed a rapidly progressing, painful swelling and redness in the cervicofacial region. After diagnosing NF based on clinical symptoms, laboratory parameters, and CT, the patients were treated with systemic antibiotics and multiple extensive debridements. Two of the three patients died within 48 h from systemic illness with septic organ failure; one patient was discharged after intensive care treatment and reconstruction of the tissue defects caused by debridement. NF is a fast-developing soft tissue infection associated with high mortality and morbidity, and is often recognized too late. Diagnosis is based on clinical signs such as progressive diffuse swelling, pain, erythema, and early systemic illness. Laboratory parameters (Laboratory Risk Indicator for Necrotizing Fasciitis [LRINEC] score) and imaging via CT or MRT are helpful. CT/MRT images can show soft tissue swelling with pathognomonic gas formation. Immediate surgical debridement and antimicrobial therapy are critical for survival. Intravenously administered immunoglobulins and hyperbaric pressure therapy should only be used as supplementary treatments.

[Exosomes as immune regulators in head and neck cancer]. / Exosomen als Immunregulatoren in Kopf-Hals-Karzinomen.

Exosomes, virus-sized nanovesicles, are utilized as messenger systems of our body to communicate with other body cells and regulate immune functions. Almost all cells produce exosomes and are able to interact with immune cells in the blood stream and peripheral body areas. Different markers on the surface of exosomes are necessary for immune cell adhesion and interaction. Furthermore, many types of exosome-immune cell interaction, such as surface receptor contact and phagocytosis, are known. As carriers of different cargos, exosomes affect different immune cell types in head and neck cancers: So far, T cells, natural killer cells, macrophages, and dendritic cells have been described in this context. For diagnostic purposes, a combined analysis of different parameters including protein amount, nucleic acid/protein expression, and the immunosuppressive impact of exosomes could empower exosomes as useful tools for evaluation of tumor promotion and progression in the future.

Hypophysitis caused by ipilimumab in cancer patients: hormone replacement or immunosuppressive therapy.

Ipilimumab is besides the BRAF inhibitor vemurafenib the first officially approved medical treatment for metastatic melanoma, which results in improved survival. Ipilimumab leads to a release of a CTLA4-mediated inhibition of T-cell immunoreactions. Therefore, patients may also suffer from immune-related adverse events affecting different organs, which are typically treated by high-dose corticosteroids. Ipilimumab-induced hypophysitis (iH) has been reported in up to 17% of melanoma patients in clinical trials.Here we present 5 patients with metastatic melanoma and 2 patients with prostate cancer who developed hypophysitis after ipilimumab therapy. Patients were treated by high-dose corticosteroid therapy resulting in the resolution of local inflammation but not of pituitary deficiencies. Partial or complete hypopituitarism remained in all patients. Pharmacotherapy with high-dose corticosteroids caused complications in 5 patients, necessitating hospitalization in 4. 2 of the 3 patients with progressive disease died, while 3 patients had stable disease and 1 patient showed tumor regression after discontinuation of ipilimumab.In summary, with regard to safety and simplicity of hormonal substitution therapy we have to scrutinize high-dose corticosteroid therapy, though it only improves inflammation but not neuro-endocrine function and may cause further morbidity. Regression of the tumor depends on the ipilimumab-mediated immune events, in which high-dose and long-term corticosteroid therapy for iH appears to be counter-intuitive. Herein, we discuss screening and the diagnostic as well as therapeutic management of iH in metastatic cancer patients from an endocrinologic perspective.

Automatic face classification of Cushing's syndrome in women - a novel screening approach.

OBJECTIVE: Cushing's syndrome causes considerable harm to the body if left untreated, yet often remains undiagnosed for prolonged periods of time. In this study we aimed to test whether face classification software might help in discriminating patients with Cushing's syndrome from healthy controls. DESIGN: Diagnostic study. PATIENTS: Using a regular digital camera, we took frontal and profile pictures of 20 female patients with Cushing's syndrome and 40 sex- and age-matched controls. MEASUREMENTS: Semi-automatic analysis of the pictures was performed by comparing texture and geometry within a grid of nodes placed on the pictures. The leave-one-out cross-validation method was employed to classify subjects by the software. RESULTS: The software correctly classified 85.0% of patients and 95.0% of controls, resulting in a total classification accuracy of 91.7%. CONCLUSIONS: In this preliminary analysis we found a good classification accuracy of Cushing's syndrome by face classification software. Testing accuracy is comparable to that of currently employed screening tests.

Healthy obese and post bariatric patients - metabolic and vascular patterns.

OBJECTIVE: Obesity and the metabolic syndrome (MetS) are associated with endothelial dysfunction (ED). An established method to determine ED is retinal vessel analysis. Obesity is associated with MetS, but obese patients not matching all criteria of the MetS and therefore defined as metabolically healthy obese subjects (MHOS) exist. Bariatric surgery may be an appropriate option to treat morbid obesity. The aim of this study was to compare MetS, MHOS and post bariatric patients in adipocytokine -patterns and ED. METHODS: Arterio-venous ratio (AVR) and vessel diameters from retinal photographs (IMEDOS™), parameters of MetS (IDF) and obesity-associated factors (hsCRP, TNF, Il-6, MCP-1, sICAM, sVCAM, IGF-BP3, RBP 4 and adiponectin) were assessed in 51 obese patients with MetS, 20 obese patients without MetS and 21 patients pre and post bariatric surgery. RESULTS: Bariatric surgery improved ED as reflected by AVR and venous diameters (p<0.05 for both). These improvements were associated with lower levels of fasting plasma glucose, insulin, HOMA-IR, LDL-C, triglycerides, cholesterol, hsCRP, sICAM, and higher levels of adiponectin and RBP4 (p<0.05 for each parameter). MHOS differed from MetS by neck circumference, fasting plasma glucose, HOMA-IR, triglycerides, HDL-C, sICAM, and adiponectin (p<0.05), but not by RRs, RRd, insulin, LDL-C, hsCRP, Il-6, TNF, MCP-1, sVCAM, RBP-4, IGF-BP3, and retinal ED. CONCLUSION: These data indicate that improved insulin-sensitivity and reduced inflammatory mediators characterize the metabolic outcome of postbariatric patients in comparison to MHOS. Thus, MHOS characterizes an intermediate state between MetS and postbariatric patients.

Neuro-endocrine and neuropsychological outcome after aneurysmal subarachnoid hemorrhage (aSAH): a prospective cohort study.

OBJECTIVE: Neuropsychological sequelae are common after aneurysmal subarachnoid hemorrhage (aSAH) and may be associated with or caused by supposed hypothalamic-pituitary dysfunction. We evaluated the incidence of neuro-endocrine and neuropsychological deficits after aSAH and their interrelations in a standardized manner. METHODS: 26 patients (20 females) were prospectively screened for neuro-endocrine and neuropsychological deficits 3 and 6 months after aSAH. We measured GH, IGF-1, prolactin, LH, FSH, estradiol, TSH, fT4, total T3, testosterone, ACTH as well as cortisol before and after ACTH-stimulation. Neuropsychological analysis covered verbal comprehension, short term and working memory, visuospatial construction, figural memory, psychomotor speed, attention, and concentration. RESULTS: After 3 months central hypogonadism was observed in 2 patients accompanied by central hypothyroidism in 1 male subject. Central hypogonadism resolved spontaneously after 6 months in both. After 3 months, neuropsychological deficits were detected in 57% of the examined patients (44% attention deficits, 38% memory impairment, 12% psychomotor deficits). Neuropsychological deficits were still present in 53% after 6 months. CONCLUSION: We found a low prevalence of neuro-endocrine and a high prevalence of neuropsychological deficits in patients 3 and 6 months after aSAH. Thus, the absent co-incidence of central hormonal and psychological dysfunction leaves a causal association questionable.

SOM230 (pasireotide) and temozolomide achieve sustained control of tumour progression and ACTH secretion in pituitary carcinoma with widespread metastases.

Pituitary carcinomas are rare and neurosurgically challenging lesions, as they commonly relapse after surgical removal. Their prognosis is dismal due to their limited response to radiotherapy and chemotherapy. In recent studies, temozolomide was administered in very few patients with partial effects. We report a patient with an ACTH-secreting pituitary carcinoma and widespread intracranial, spinal and systemic metastases despite repeated surgical treatment, bilateral adrenalectomy, medical treatment and radiotherapy. Additionally to chemotherapy with temozolomide, the patient received SOM230 as salvage therapy with an improvement of the patient's clinical status, and a reduction of ACTH levels. After 12 months of combination therapy a sustained tumor control was achieved and persisted upon monotherapy with SOM230 for more than 9 months thereafter. Thus, temozolomide in combination with SOM230 seems to be promising in patients with ACTH-secreting metastasized pituitary carcinoma.

Clinical benefit of a short term dietary oatmeal intervention in patients with type 2 diabetes and severe insulin resistance: a pilot study.

AIMS/HYPOTHESIS: To evaluate the potential effectiveness of 'carbohydrate days' as a dietary intervention to overcome insulin resistance in type 2 diabetes. MATERIALS AND METHODS: Patients (n=14) with uncontrolled type 2 diabetes and insulin resistance as defined by a dosage of more than 1 IU/day (*)kg BW were consecutively enrolled in this prospective study. Primary outcomes were daily insulin requirement and mean blood glucose levels which were evaluated before, after, and 4 weeks after the intervention. RESULTS: All patients had a metabolic syndrome, 75% had microvascular and 57.1% macrovascular complications. Hospital setting and diabetes adapted diet alone led to improved glycemic control with a mean blood glucose 158+/-47 mg/dl. Intervention with two days of oatmeal diet further decreased mean blood glucose to 118+/-37 mg/dl (p<0.05). This was associated with a significant reduction of insulin dosage by 42.5% (before: 145+/-68.9 U/d, after 83+/-34.2 U/d, p<0.001) as well as a significant reduction (-26.4%, p<0.01) of serum leptin levels. After the four weeks outpatient period, insulin dosage remained significantly decreased (83+/-20.2 U/kg (*)d, p<0.01). Glycemic control was comparable (mean blood glucose141+/-20.78 mg/dl) to glucose levels within the hospital setting. Adiponectin levels increased significantly by 53.8% (p<0.05). CONCLUSIONS: In this uncontrolled pilot study, hospital admission and diabetes adapted diet followed by oatmeal intervention achieved a approximately 40% reduction of insulin dosage required to achieve controlled glucose levels. This effect was conserved after a 4 week outpatient phase with normal diet.

Biomimetic evolutionary analysis: testing the adaptive value of vertebrate tail stiffness in autonomous swimming robots.

For early vertebrates, a long-standing hypothesis is that vertebrae evolved as a locomotor adaptation, stiffening the body axis and enhancing swimming performance. While supported by biomechanical data, this hypothesis has not been tested using an evolutionary approach. We did so by extending biomimetic evolutionary analysis (BEA), which builds physical simulations of extinct systems, to include use of autonomous robots as proxies of early vertebrates competing in a forage navigation task. Modeled after free-swimming larvae of sea squirts (Chordata, Urochordata), three robotic tadpoles (;Tadros'), each with a propulsive tail bearing a biomimetic notochord of variable spring stiffness, k (N m(-1)), searched for, oriented to, and orbited in two dimensions around a light source. Within each of ten generations, we selected for increased swimming speed, U (m s(-1)) and decreased time to the light source, t (s), average distance from the source, R (m) and wobble maneuvering, W (rad s(-2)). In software simulation, we coded two quantitative trait loci (QTL) that determine k: bending modulus, E (Nm(-2)) and length, L (m). Both QTL were mutated during replication, independently assorted during meiosis and, as haploid gametes, entered into the gene pool in proportion to parental fitness. After random mating created three new diploid genotypes, we fabricated three new offspring tails. In the presence of both selection and chance events (mutation, genetic drift), the phenotypic means of this small population evolved. The classic hypothesis was supported in that k was positively correlated (r(2)=0.40) with navigational prowess, NP, the dimensionless ratio of U to the product of R, t and W. However, the plausible adaptive scenario, even in this simplified system, is more complex, since the remaining variance in NP was correlated with the residuals of R and U taken with respect to k, suggesting that changes in k alone are insufficient to explain the evolution of NP.

Adult vascular progenitor cells and tissue regeneration in metabolic syndrome.

Adult vascular progenitor cells (for example endothelial progenitor cells, EPC) have been studied for their contribution to vascular repair and angiogenesis. These cells can differentiate from bone marrow cells as well as circulating cells carrying hematopoetic stem cell markers. In vivo, they take part in vasculogenesis in different animal models of limb ischemia, myocardial infarction and wound healing. In metabolic disease, the outgrowth and function of EPC in vitro is defective and numbers of EPC correlate with classical risk factors of cardiovascular disease suggesting a role of EPC in the development of vascular complications. Pilot studies for the treatment of myocardial infarction and limb ischemia with autologous bone marrow showed a distinct therapeutic benefit that is presumably mediated by vasculogenesis in damaged tissues. However, little is known about the nature of EPC and their capability to differentiate into functional cells for tissue regeneration. In this article, we review and discuss the hitherto identified physiological function of EPC, the mechanisms leading to dysfunction of these cells and potential therapeutic applications in patients with metabolic syndrome or diabetes mellitus and vascular complications.

Serum resistin levels of obese and lean children and adolescents: biochemical analysis and clinical relevance.

OBJECTIVE: It was hypothesized that resistin links obesity with diabetes, but this has not been studied in children and adolescents to date. PATIENTS: We determined serum resistin levels of 135 obese (body mass index, 32.0 +/- 6.2 kg/m2; age, 12.6 +/- 3.4 yr) and 201 lean children (body mass index, 18.7 +/- 2.4 kg/m2; age, 12.5 +/- 2.5 yr) by a newly developed and extensively evaluated in-house immunoassay. These results were controlled for their association with markers of puberty, obesity, and insulin sensitivity. RESULTS: The analytical evaluation of our assay revealed different resistin isoforms with major peaks of higher than 660 and 55 kDa in the size exclusion chromatography. Using this assay system we found no difference in the resistin levels of obese compared with lean subjects (P = 0.48). However, resistin was significantly higher in girls than in boys (6.74 +/- 2.42 vs. 5.79 +/- 2.45; P < 0.001). Interestingly, in both obese and lean children, resistin correlated with age (P < 0.01), Tanner stage, and testosterone and estradiol levels (P < 0.05). In contrast, no significant correlation was found with parameters of insulin resistance such as homeostasis model assessment, insulin sensitivity index, or insulin, proinsulin, and glucose concentrations in obese subjects. CONCLUSIONS: Resistin appears to be not the main link between obesity and insulin resistance in children and adolescents but because of its association with Tanner stage, it may be related to the maturation of children during pubertal development. Additionally, we have demonstrated the presence of different molecular isoforms of resistin in human blood, and this may raise problems in comparing data from diverse assay systems.

Leptin and leptin receptor in human seminal plasma and in human spermatozoa.

Leptin, a 167 amino acid peptide, is known to influence the gonads via direct and indirect effects. Recent studies provide contradictory proposition about the peripheral impact of leptin in the male gonads. Thus, we examined leptin and its receptors in human seminal plasma and in human ejaculated spermatozoa by Western blot technique and fluorescence microscopy. In seminal plasma we found a free leptin band (16 kDa) by an anti-leptin polyclonal antibody. Incubation of seminal plasma with recombinant leptin caused a statistically significant increase in the amount of free leptin (p < 0.01) and supports this finding. Furthermore, a soluble leptin receptor (145 kDa) was found in human seminal plasma in the same specimen. We also detected a 145-kDa leptin receptor isoform in ejaculated spermatozoa as a possible target of leptin action in the male genital tract, which was localized at the tail of spermatozoa by immunofluorescence microscopy only. This receptor was significantly associated with the intactness of sperm plasma membranes. Spermatozoa with deteriorated membranes contained 49.2 +/- 6.9% leptin receptor signal intensity compared with spermatozoa having intact membranes (p < 0.01). This finding is difficult to interpret and may be caused by a leakage of OB-R due to loss of membrane integrity. In conclusion, these data provide further hints for a peripheral role of leptin in the male genital tract, possibly, by an interaction between leptin and spermatozoa via sperm leptin receptors.

Different isoforms of the soluble leptin receptor in non-pregnant and pregnant mice.

Leptin circulates in murine serum in a free and a bound form. As shown in humans, a soluble leptin receptor (sOB-R), which modulates the effects of its ligand, circulates in murine blood. The aim of our study was to determine abundance and biochemical nature of this protein. For the quantification of sOB-R we developed a ligand-immunofunctional assay (LIFA) which is based on both, leptin binding and immunological recognition. The use of this LIFA revealed that during late gestation sera of pregnant mice had a approximately 290-fold higher level of sOB-R than non-pregnant animals. As investigated by size exclusion chromatography these mice sera demonstrated a co-elution of their leptin binding activity with leptin immunoreactivity and levels of sOB-R measured by LIFA. Therefore, it has to be concluded that sOB-R represents the major leptin binding activity in murine circulation. The molecular analysis of sOB-R by Western blot and by cross-linking with 125I-leptin in sera of pregnant and non-pregnant mice demonstrated two different isoforms of sOB-R, which were capable of leptin binding. The sOB-R in serum migrated at a molecular weight of 150kDa in pregnant and only of 120kDa in non-pregnant animals. Deglycosylation of these isoforms led to sOB-R molecules which were found at the same molecular weight in SDS-PAGE. This finding indicates that both isoforms differ only in the degree of their glycosylation. In conclusion, the non-pregnant and the pregnant states are accompanied by differently glycosylated isoforms of sOB-R whose physiological relevance remains to be determined.

Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence.

Leptin is bound in human blood by a high affinity binding protein, which appears to be identical with the soluble leptin receptor (sOB-R). Using a ligand-mediated immunofunctional assay for the determination of serum sOB-R, we investigated its course during childhood, puberty, and adolescence in a large cohort of 581 healthy children and adolescents and a small group of 13 patients with anorexia nervosa. In the first years of life, sOB-R is detectable in remarkably high concentrations. Thereafter, a continuous decline of sOB-R levels was found. Consequently, correlation analyses demonstrated significant inverse relationships (P < 0.001) of sOB-R with age, IGF-I levels, pubertal stage, auxological and body composition parameters, as well as with leptin concentrations. Multiple regression analysis revealed that height, IGF-I, and age (only in girls) were independent predictors of sOB-R levels; these variables account for approximately 65% and 48% of the variation of sOB-R levels in boys and girls, respectively. The courses of age-dependent median values for the free leptin index (FLI, ratio between leptin and sOB-R levels) and for leptin levels were parallel in both genders. Correlation analyses demonstrated that in particular parameters of growth and sexual maturation are more closely related to the FLI than to leptin alone; this closer relationship is more pronounced among boys. Weight gains of patients with anorexia nervosa resulted in a significant increase in leptin and IGF-I levels (P < 0.01), whereas the median of sOB-R values decreased (P < 0.01). sOB-R and IGF-I levels were again significantly correlated (r = -0.55, P < 0.01). These findings suggest that high levels of sOB-R in emaciation may reflect an up-regulation of the sOB-R to suppress leptin action during energy deficiency. Furthermore, determinations of sOB-R and FLI are additional valuable tools to investigate the leptin axis during growth and sexual maturation.

Leptin exists in tubuli seminiferi and in seminal plasma.

Leptin is a 167-amino acid protein that stimulates gonadotrophin-releasing hormone secretion and exerts indirect effects on the gonads via neuropeptide Y, NPY. Recent research has suggested that leptin may also have an effect on testosterone secretion. To investigate the role of leptin in reproduction, leptin in testicular tissue and seminal plasma was examined in relation to leptin in serum, semen sample qualities and vasectomy. Seminal plasma and serum of 64 infertility patients, and 15 individuals after vasectomy, were assayed for leptin using a competitive 'in house' radioimmunoassay. The concentration of leptin in seminal plasma was significantly lower in the 'normal' semen sample group than in the 'pathological' group (Mean +/- SEM; 1.45 +/- 0.18 vs. 3.19 +/- 0.57 ng ml-1; P < 0.05), and showed a significantly negative correlation with percentage of motile spermatozoa (r = -0.46; P = 0.0005) and with the velocity straight line, VSL, (r = -0.30; P = 0.029). In contrast, leptin concentration in serum did not show any relationship with the spermiogram parameters. In testicular tissue, leptin was preferentially found within the tubuli seminiferi using anti-leptin polyclonal antibody, Ob A-20 Sc 842. The amount of leptin per ejaculate did not significantly change after vasectomy, and was not correlated to fructose, zinc or neutral alpha glucosidase in seminal plasma (P > 0.05). These results suggest that the amount of leptin in the genital tract, including the tubuli seminiferi, may influence the mechanisms involved in the motility development of spermatozoa.

Soluble leptin receptor represents the main leptin binding activity in human blood.

In human blood leptin circulates both free and bound to high molecular weight proteins. Hypothesising that these proteins may modulate ligand bioavailability and bioactivity of leptin, we investigated their molecular nature. Therefore, leptin binding activity was partially purified from human plasma using a leptin affinity column. Subjecting this preparation to size exclusion chromatography (SEC) we observed a coelution of leptin binding activity with levels of the soluble leptin receptor (sOB-R) determined by a newly developed ligand immunofunctional assay. In Western blot analysis the partially purified leptin binding activity exhibited sOB-R immunoreactivity in two bands of 110 and 140 kD. Following N-deglycosylation these bands were replaced by two bands with the molecular weight of 90 and 60 kD, suggesting two isoforms which are capable of leptin binding, as determined by cross-linking. Furthermore, different ratios of these isoforms were detectable in fractions of the leptin binding activity after separation by SEC. These findings indicate the formation of heterodimers and homodimers complexed with and without leptin. As the two sOB-R bands from Western blot analysis correspond to only two specific bands in cross-linking experiments with 125l-leptin, the role of both isoforms as leptin binding proteins appears to be exclusive. Therefore, our results indicate that sOB-R is the major leptin binding protein in the circulating human blood.