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Background. Idiopathic hypercalciuria is a risk factor for nephrolithiasis. Both renal stones and hypercalciuria are associated with lower bone mineral density (BMD), but the relationship between these modifications is not completely understood. Aims. To evaluate some metabolic particularities possibly related to relapsing nephrolithiasis (RN) in young male patients. Methods. We performed a crosssectional study including a group of 30 young male patients with RN and a group of 30 healthy, age and BMI (body mass index) matched controls (CTR). We evaluated calcium and phosphate metabolism, bone remodeling markers alkaline phosphatase (AP) and osteocalcin in serum and 24-hour urine samples, and lumbar and hip BMD. Results. We observed higher values of serum calcium (P<0.05) and 24 hour urinary calcium (P<0.001) in the RN group. Parathyroid hormone (PTH) and AP were also higher in the RN group (P<0.01), whereas serum 25OH-D3 was lower (P<0.01). BMD, T and Z scores were lower in the RN group in both the lumbar (P<0.01) and hip (P<0.05) regions. Conclusions. Young male patients with hypercalciuric RN have lower BMD and higher bone turnover. Higher PTH levels related to vitamin D deficiency may contribute to bone demineralization in certain cases. [ABSTRACT FROM AUTHOR]

Emilia Solomon,1,2 Dumitru Brănișteanu,1,3 Andrei Dumbravă,4 Radu Gheorghe Solomon,5 Lorànt Kiss,5 Mihai Glod,1 Cristina Preda1,3 1Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania; 2Department of Endocrinology, CF University Hospital, Iaşi, Romania; 3Department of Endocrinology, “Sf. Spiridon” Hospital, Iaşi, Romania; 4Faculty of Psychology, Alexandru Ioan Cuza University, Iaşi, Romania; 5ISUD, Faculty of Medicine, University Lucian Blaga, Sibiu, Romania Introduction: Active acromegaly is a rare chronic endocrine disorder caused by excessive growth hormone (GH). Clinical studies suggest that cognitive performance is impaired in acromegaly – particularly executive function as well as short- and long-term memory. This study compared the quality of life (QoL) and executive functioning in acromegaly patients vs healthy controls.Materials and methods: This was an observational case–control study on 38 subjects divided into 19 acromegaly patients and 19 matched controls. The groups were evaluated for QoL, attention, and executive function. All subjects completed Acromegaly Quality of Life Questionnaire (AcroQoL), Trail Making Test (parts A and B), Stroop, and phonemic fluency tests.Results: Acromegaly patients had an AcroQoL global score that was significantly lower than controls. There were significant differences between the acromegaly group and the control group in terms of the physical effects (P=0.001) and appearance (P

Aims: we wanted to check the importance of sunlight exposure and vitamin D supplementation in reverting secondary hyperparathyroidism at IIIrd age institutionalized patients. Design: cross-sectional study of calcium and bone metabolism in a group of 123 institutionalized IIIrd age volunteers after winter period, followed by a prospective double blind placebo-controlled study of effects upon calcium and bone metabolism, serum 25OH-D3, 1,25(OH)2D3 and PTH levels of daily sunlight exposure during the summer months, with or without vitamin D supplementation (2000 IU 25OH-D3 po, daily). The study was performed on volunteers from the Elderly Resting House of Copou, Iasi, Romania. 25OH-D3 was measured by an inhouse RIA technique. 1,25(OH)2D3 was measured by HPLC, serum calcium by photocolorimetry, bone alkaline phosphatase by immunoenzymatic technique, whereas serum PTH and urinary deoxypyridinoline (DPD) were measured by IRMA. Data was compared using Student's t test and correlation analysis (R²). Almost all volunteers (93.5%) had low 25OH-D3 values, but normal or even increased levels of the active hormone, 1,25(OH)2D3. High PTH was found in 41 cases (33.3%), of which three were primary hyperparathyroidism, whereas the others had low or low-normal calcium levels (secondary hyperparathyroidism). More than half of the cases had high DPD levels, suggesting high bone turnover. Bone turnover parameters were higher in females than in males (p<0.05). A positive correlation between PTH and urinary DPD was noticed (R²=0.351). We further supplemented the vitamin D intake in 42 volunteers with a daily dose of 2000 IU of 25-OHD3 for three months in the summer period, whereas other 42 volunteers received placebo (vitamin B). Normalization of 25-OHD3 levels was seen in both vitamin D and placebo-treated sun-exposed groups. A more significant increase in 25OH-D3, and also of 1,25(OH)2D3 at the upper limit of normal was however observed in the vitamin D-treated group. Normalization of serum PTH, but not of turnover parameters was observed in both groups. Mild hypercalcemia and increase in serum creatinine were noticed in the vitamin D-treated group. Conclusions: Secondary hyperparathyroidism might be of importance in high turnover bone loss at institutionalized IIIrd age patients. Women seem to be more at risk, possibly due to sex hormone depletion. PTH-induced 1α hydroxylation in the elderly with undamaged kidney function partially compensates the paucity of vitamin D substrate, by normalizing active hormone levels. Mild sun exposure at institutionalized patients increases skin resources of vitamin D, normalizing 25OH-D3 levels and reverting secondary hyperparathyroidism. Oral vitamin D supplementation added to sunlight exposure should be done with caution, since it might be accompanied in certain patients by hypercalcemic or nephrotoxic effects at doses higher than 2000 IU/day. [ABSTRACT FROM AUTHOR]

Vitamin D is one of the key factors in calcium and bone metabolism. Presently more than 30 natural vitamin D metabolites are known, but only la,25- dihydroxyvitamin D3 [1,25(OH)2D3], synthesized under the action of kidney Ia hydroxylase, is considered as being the final active hormonal product (1). The "classical" targets of 1,25(OH)2D3 are the gut, the bone and the kidney, all these organs possessing vitamin D receptors (VDR). l,25(OH)2D3 controls active intestinal absorption of calcium and phosphate, kidney calcium reabsorption, as well as bone metabolism, by acting directly on osteoblasts that possess VDR, and favoring osteoclast differentiation from monocytic precursors (2). In pharmacological doses, 1,25(OH)2D3 becomes toxic, increasing osteoclast formation and bone turnover, and thus leading to toxic effects (rapid bone loss, hypercalcemia, soft tissue calcifications). These toxic effects seem to be cytokine (IL-il) and prostaglandin-mediated (1). 1 ,25(OH) D3 acts through specific intracellular (nuclear) receptors from the same superfaniily as the retinoic acid, steroid and thyroid hormone receptors. Although there is only one vitamin D receptor (VDR) gene located on chromosome 12q13-14, alternate splicing leads to VDR isoforms, of which two most widespread are the f and F isoforms. The longer isoform, f (Mi), has 427 aminoacids, whereas the shorter VDR isoform, F (M4), has 424 aminoacids, lacking 3 aminoacids at the aminoterminal region (3). The VDR binds as a homodimer or as a heterodimer with the retinoid X receptor (RXR), to specific DNA sequences called vitamin D responsive elements (VDRE), situated in the promoter region of various vitamin D responsive genes (4). Coupling of 1,25(OH)2D3 to the VDR increases the affinity of the dimeric receptor complex to the VDRE. As a consequence of this binding, transcriptional activity is modulated through influencing RNA polymerase activity, a process called transactivation (4). Gene transcription is thus up- or down regulated, producing a specific cellular response. Rapid, "non-genomic" actions of l,25(OH)2D3 have also been described in various cell types (5). VDRs are found not only in the classical tissue targets for vitamin D, but also in other cells or tissues that are not involved in the calcium and bone metabolism, such as the brain and brain stem, muscles, thyroid follicular and parafollicular C cells, gonads, pituitary, endocrine pancreas, adrenal gland, prostate, uterus, hair follicle, tumor cells and cells of the immune system (6-9). The presence of the VDR in these tissues suggests that 1,25(OH)2D3 might play other roles than a mere calcium regulator. Indeed, 1 ,25(OH)2D3 has several non-classical or non-calcemic effects, such as inhibition of proliferation and differentiating effects in normal cells (keratinocytes), as well as tumoral cells (colon, prostate, thyroid and breast cancer, or leukemia cells) (9), or modulation of the immune response (9-11). [ABSTRACT FROM AUTHOR]

The hormone lα, 25 dihydroxyvitamin D3 (l,25(OH)2D3) has potent immunosuppressive effects in vitro. Recent publications also described a protective effect of the hormone in various animal models of immune-mediated diseases. To test its in vivo activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with l.25(OH) 2D3 or its synthetic 20-epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of l,25(OH) 2D3 (0.5μg,/kg body weight) given on alternate days during the first 13 days after active immunization significantly reduced the proteinuria as measured by weeks 7-9. This reduction was comparable to the reduction observed in rats treated with CsA (20 mg/kg) on alternate days. A second series of experiments with 1,25(OH) 2D3 confirmed these findings. The level of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of significance (P=0.06) was reached in the 1,25(OH) 2D3(0.5 μg/kg) group. The size of the immune deposits also was found to be substantially smaller in the groups that developed less proteinuria. The administration of 1,25(OH) 2D3 transiently increased the mean serum calcium concentration with 2.5 mg/dl above the pretreatment values, and the urinary calcium excretion by a factor of 3-5 during the short treatment time. Treatment with the analogue KH1060 did not reduce the proteinuria significantly. Our experiments add evidence to the hypothesis that 1,25(OH) 2D3 in pharmacological doses has immunosuppressive potency. [ABSTRACT FROM AUTHOR]

The hormone lα, 25 dihydroxyvitamin D3 (l,25(OH)2D3) has potent immunosuppressive effects in vitro. Recent publications also described a protective effect of the hormone in various animal models of immune-mediated diseases. To test its in vivo activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with l.25(OH) 2D3 or its synthetic 20-epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of l,25(OH) 2D3 (0.5μg,/kg body weight) given on alternate days during the first 13 days after active immunization significantly reduced the proteinuria as measured by weeks 7-9. This reduction was comparable to the reduction observed in rats treated with CsA (20 mg/kg) on alternate days. A second series of experiments with 1,25(OH) 2D3 confirmed these findings. The level of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of significance (P=0.06) was reached in the 1,25(OH) 2D3(0.5 μg/kg) group. The size of the immune deposits also was found to be substantially smaller in the groups that developed less proteinuria. The administration of 1,25(OH) 2D3 transiently increased the mean serum calcium concentration with 2.5 mg/dl above the pretreatment values, and the urinary calcium excretion by a factor of 3-5 during the short treatment time. Treatment with the analogue KH1060 did not reduce the proteinuria significantly. Our experiments add evidence to the hypothesis that 1,25(OH) 2D3 in pharmacological doses has immunosuppressive potency. [ABSTRACT FROM AUTHOR]

Calcitonin (CT) is a polypeptidic hormone specifically secreted by the thyroid parafollicular cells (C cells) and tangentially involved in human phosphocalcic and bone metabolism. CT from other species (e.g. salmon) is more potent than human CT and has limited therapeutic applications. The neoplastic proliferation of C cells leads to medullary thyroid carcinoma (MTC) generally characterized by an increase of CT secretion. Serum CT is therefore the ideal marker for MTC and can confirm its presence at an early stage, as well as the follow up of its remission or progression/relapse/survival after surgery. There are, however, controversies such as the necessity of CT screening in patients with thyroid nodules, or particular situations causing false positive or false negative results. Our minireview also deals with an up-to-date of surgical procedures for MTC, as well as with non-surgical therapy. [ABSTRACT FROM AUTHOR]

We present the case of a 28 year old pregnant primiparous woman, suspected of primary hyperparathyroidism due to hypercalcemia discovered by routine calcium assessment at 30 weeks of gestation. Diagnosis was strongly suggested by elevated serum calcium (15.2 mg/dL, normal range: 8.4-10.3 mg/dL), low serum phosphorus (0.55 mg/dL, normal range: 2.5-5 mg/dL) and increased urinary hydroxyproline excretion (118 mg/24h, normal range: 10-40 mg/24h), suggesting high bone turnover and confirmed by coexistence of high levels of parathyroid hormone (PTH, 145 pg/mL, normal range 10-65 pg/mL). Neck ultrasound identified a solid nodule of 33x58x20.5 mm situated behind the inferior pole of a normal thyroid left lobe, suggestive for a solid parathyroid tumour located within the left inferior parathyroid gland. Medical treatment with furosemide and hydration decreased serum calcium level but failed to normalize it. After a 3 day preparation for lung maturation with dexamethasone (16 mg per day), successful adenomectomy was performed under local anaesthesia, without major intraoperative or postoperative events. The few uterine contractions were easily managed with papaverine and progesterone. Calcium levels immediately returned to normal after surgery. Our patient delivered a healthy newborn at 40 weeks by caesarean section. A DXA BMD assay performed after one year showed significant bone loss of the mother at radius level (T score of - 2.6). [ABSTRACT FROM AUTHOR]

Context. State of art imaging techniques might be a useful tool to early detect the retinal vessels lesions in diabetes. Objective and design. This analytical observational study investigates the retinal microcirculation changes in type I and II diabetic patients without retinopathy using adaptive optics ophthalmoscopy (AOO) and optical coherence ophthalmoscopy angiography (OCTA). Subjects and methods. Fifty-five subjects were included in this study and were divided in three groups: type I diabetic group (n=16), type II diabetic group (n=19) and control group (n=20). An adaptive optics retinal camera was used to assess the parameters of the temporal superior retinal arterioles. Moreover, vessel density of the superficial capillary plexus across the parafoveal area was measured with OCT-A. All cases were investigated once, in a cross-sectional design. Results. Diabetic patients from both groups had a higher wall-to-lumen-ratio compared to the controls (p=0.01 and 0.01, respectively). Interestingly, no significant differences were found between the two diabetic groups (p=0.69). Moreover, the vessel density was smaller in the type I diabetic group than in the control group (p=0.001) Conclusion. AOO might be a useful tool to detect early retinal vascular changes in diabetes before any clinical signs and together with OCTA it might bring important information on the prognostic and pathophysiology of the disease. [ABSTRACT FROM AUTHOR]

Background. Adipokine secretion is influenced by various disease conditions. Purpose. We wanted to check the impact of rectal carcinoma (RC) on adipokine profile. Patients and methods. We evaluated serum leptin and adiponectin levels in 24 RC patients (12 males and 12 females) as well as in the same number of age, sex and weight-matched healthy controls. Results. Adipokines were oppositely correlated with body weight (BW) in controls and RC patients. Women had higher adipokine levels than men. Healthy controls had higher leptin (37.6.±7.8 vs. 7.9±2.6 ng/mL in women and 11.9±4.6 vs. 1.4±0.34 ng/mL in men, p=0.0016 and 0.043) and lower adiponectin levels (9.3±1.1 vs. 14.9±1.1 µg/mL in women and 7.9±0.9 vs. 11.1±0.9 µg/mL in men, p=0.012 and 0.017) than RC patients. Conclusion. Adipokine profiles of patients with RC differ from the healthy population, possibly reflecting an adaptation to the disease rather than a triggering factor. These differences may find clinical applications for the prognosis of disease evolution. [ABSTRACT FROM AUTHOR]

Prader Willi syndrome is a complex disease caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11.2-q13. Typical clinical features are hypotonia and feeding difficulties in infancy, followed by hyperphagia and progressive obesity, distinctive dysmorphic features, intellectual disability and behavioural problems. In this paper we present clinical, metabolic and endocrine aspects in five genetically confirmed patients with PWS. Data about thyroid dysfunction, GH deficiency, adrenal insufficiency, and LH/FSH disorder caused by hypothalamic dysfunction in PWS were collected and analyzed. Cardiovascular metabolic profile was also assessed, based on plasma lipids, blood glucose, HbA1c values, and measurements of body weight and blood pressure. Clinical features present in all our patients were marked hypotonia and feeding difficulties in infancy, obesity, dysmorphic face, viscous saliva, small hands and feet, intellectual disability and characteristic behaviour. Adrenal function appeared to be normal in all patients; mild hypothyroidism was identified in one patient; sex development abnormalities were present in three patients and GH levels were within lower normal range in all patients. GH therapy was initiated in two patients, both with unevolutive skeletal anomalies, with good results and no side-effects. Only one patient had a normal lipid profile, underlying the importance of early detection and treatment of cardiovascular risk factors. Our study also illustrates the challenges raised by some features very rarely described in PWS (Blount disease and multiple allergies). [ABSTRACT FROM AUTHOR]

Introduction. Orbitopathy is a common extrathyroidal feature of Graves' disease. Initial immune infiltration may be followed by irreversible fibrosis and hypertrophy of extraocular muscles, leading to exophthalmos, diplopia and optic nerve compression. Surgery can improve the quality of life by adapting orbit volume to its content through orbital expansion and/or decompression and through interventions for functional or aesthetical reasons. Aim. To evaluate the impact of orbit surgery on the evolution of Graves' ophthalmopathy. Patients and Methods. Our series includes 21 patients, operated between 2006 and 2012 mainly for proptosis (16 cases) or diplopia (5 cases). Results. Emergency orbit decompression was performed in one patient in the acute phase due to vision loss, reversible after intervention. Orbital extraconal lipectomy was used in all patients, involving both intraconal and extraconal fat in five cases. Unilateral bone decompression was needed in two interventions. 7 patients developed upper eyelid retraction, treated with botulinum injection in the levator palpebrale. Another patient showed lower lid retraction, elongated with palatal mucosal graft. Conclusion. Adequate surgery should be chosen for each case in an integrated multidisciplinary approach. Both intraorbital fat removal and bone decompression could be concomitantly used in certain patients with severe orbitopathy. Surgery should be performed in stabilized orbitopathy, but emergency intervention might be beneficial in acute onset of vision loss due to optic nerve compression. [ABSTRACT FROM AUTHOR]

Ehlers-Danlos syndromes (EDS) represent a group of rare inherited disorders that affect connective tissues. There are 13 types of disease, most of them affecting joints or skin; symptoms usually include loose joints, joint pain, stretchy velvety skin, abnormal scar formation. However, the most serious type of disease is vascular EDS (vEDS), or EDS type 4 because patients may suffer vessels dissections or internal organs lesions, followed by bleeding, which endangers patient's life, but also thromboembolic events. We present two clinical cases of vEDS managed in our clinic in 1 year distance. In both cases, patients were active young persons (in their thirties, and respectively, twenties), both with multiple non-traumatic vascular dissections, and severe ocular complications: arterio-venous fistula with massive exophthalmia, and central retinal artery occlusion, respectively. Both cases were challenging since the life of the patients were threatened by their condition. However, in both cases, prompt treatment and finding the right trigger of the ocular pathology and vascular injuries helped doctors to provide proper and prompt medical care, in order to prevent future similar events to happen and to preserve a good quality of life for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cherecheanu, Romanitan, Pirvulescu, Iancu, Garhöfer, Iancu, Cherecheanu, Zemba, Vasile, Simonov and Branisteanu.)

The present paper explores genetic polymorphism and its association with thromboembolic retinal venous disorders, such as central/hemi-retinal vein occlusion, as well as possible correlations with other ocular findings, such as closed angle glaucoma, but also with autoimmune general disorders. In this review, we are highlighting the importance of establishing a correspondence between all of the above, since they all have complex etiopathogeneses; sometimes, when all coexist together, they could generate effects that may be very difficult to manage. There are studies supporting that genetic polymorphism, such as the variant MTHFR A1298C, may increase the risk for developing glaucoma, especially in the heterozygote model. Being aware of all these aspects may prove to be useful in patients with several associated diseases, as a combined effort between several medical specialties may prove to the benefit of these patients. Our review, completed with an exemplifying clinical case, shows that it is necessary to raise awareness of all aspects of a complex medical situation, including the genetic one, of a patient being at risk for thromboembolic episodes, for preventing them or managing them promptly and properly in the future.

The skin is an organ with multiple functions, where important inflammatory and immunological processes take place. The integrity of the skin barrier is necessary for it to fulfill its roles. An intact skin barrier requires a physiological keratinization process, but also a normal cutaneous microbial flora. Any change in the proliferation and differentiation of keratinocytes entails the disruption of the skin barrier and the triggering of inflammatory and immunological processes at this level, in response to the aggression of external pathogens. Also, there are several specialised immune cells in the skin (Langerhans cells, T regulator cells, T helper cells), that maintain a balance between pro-inflammatory and anti-inflammatory processes at this level. Disturbing the immune homeostasis causes inflammation and allergic skin reaction. Psoriasis and atopic dermatitis are two inflammatory diseases of the skin, characterized by perturbation of the mechanisms of skin barrier formation. The immune system of the skin is also involved in the pathophysiology of vitiligo and pemphigus. The aim of this review is to offer a brief presentation of the inflammatory and immunological processes that occur in the skin., (Copyright © 2020, Spandidos Publications.)

Clinical studies investigating the relationship between fibroblast growth factor 23 (FGF23) and bone mass are controversial, especially in the healthy renal population. Our study is one of the forefronts investigating the relationship between FGF23 and bone mass parameters in the general population, according to age, sex, menopausal, and nutritional status. Cross-sectional study enrolling 123 volunteers between 20-80 years of age without primary osteoporosis under treatment nor secondary osteoporosis, where bone mass (bone mineral density-BMD, bone mineral content-BMC; assessed by Dual X-Ray Absorptiometry-DXA), body composition (DXA evaluation), and also the serum levels of FGF23, parathormone (PTH), 25(OH)D, bone resorption marker C-terminal telopeptide of type I collagen (CTx) and leptin were determined. FGF23 was negatively and independently associated with BMD and/or BMC in all groups. FGF23 contributed to up to 10% (p <0.05) of femoral neck BMD variance in postmenopausal women, but was not an accurate discriminator of normal versus low bone mass (AUC=0.622±0.076). FGF23 did not correlate with 25(OH)D, CTx, body weight, body composition parameters or leptin. FGF23 was independently associated with PTH in premenopausal women and men only. FGF23 was negatively associated with bone mass parameters in both sexes, but was not a fine discriminator between normal bone mass and osteopenia/osteoporosis. The mechanism through which FGF23 acts upon the bone seems independent of the nutritional status, requiring further investigation., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Data regarding the role of fibroblast growth factor 23 (FGF23) in primary hyperparathyroidism (PHPT) are scarce and discordant. Our study aimed to evaluate the prognostic impact of FGF23 upon the clinical and biochemical evolution of PHPT., Material and Methods: Forty-two patients with ages between 30 and 80 years, diagnosed with PHPT caused by a sporadic, solitary parathyroid adenoma, and referred to surgery (minimally invasive parathyroidectomy) were prospectively included in the study. Serum levels of FGF23, PTH, 25(OH)D3, calcium (Ca), phosphate (P), total procollagen type 1 N-terminal propeptide, and C-terminal telopeptide of type I collagen were determined at baseline (preoperatory), one day after surgery, and in 13 patients also prospectively at three, six, and 12 months. Bone mineral density (BMD) was also evaluated before surgery in all patients and 12 months after surgery in the 13 followed up patients., Results: In the 42 PHPT patients with D hypovitaminosis (mean 25(OH)D3 levels of 16.2 ± 1.5 ng/mL), preoperatory serum FGF23 concentration was within the normal range (75.55 ± 3.39 pg/mL) and remained unchanged one day post operation (81.69 ± 4.67 pg/mL, p = non-significant). The 13 patients followed prospectively for up to 12 months after surgery also showed unmodified FGF23 levels (80.9 ± 11.03 pg/mL, p = non-significant), despite PTH and Ca normalisation and vitamin D replenishment. Preoperatory FGF23 negatively correlated with PTH (r = -0.37, p = 0.038), but not with 25(OH)D3, Ca, P, bone mass, or metabolism markers., Conclusions: In PHPT, correlations between FGF23 and PTH seem rather an epiphenomenon. Therefore, we think that FGF23 evaluation and dynamics are not informative regarding PHPT severity. (Endokrynol Pol 2020; 71 (4): 306-312).

Background: Numerous studies associate adipokines with colorectal malignancy, but few data deal with patients suffering exclusively of rectal carcinoma (RC)., Aims: We evaluated leptin and adiponectin levels in RC patients compared to healthy population and their dynamics after surgery., Material and Methods: Serum leptin and adiponectin were evaluated before surgery in 59 RC consecutive patients (38 males and 21 females), and in age and weight matched healthy controls. Measurements were repeated at 24, 72 hours and 7 days after surgery., Results: Adipokine levels were higher in women. Controls had higher leptin (32.±4.34 vs 9.51±1.73 ng/ml in women and 11±2.66 vs 2.54±0.39 ng/ml in men, p = 0.00048 and 0.0032) and lower adiponectin (9±0.64 vs 11.85±1.02 μg/ml in women and 7.39±0.51 vs 8.5±0.62 μg/ml in men, p = 0.017 and 0.019) than RC patients. Surgery caused an increase of leptin from 5.11±0.8 to 18.7±2.42 ng/ml, p = 6.85 x 10¨8, and a decrease of adiponectin from 9.71±0.58 to 7.87±0.47 μg/ml, p = 1.4 x 10¨10 for all RC patients and returned thereafter to the initial range at 7 days. Adipokines were correlated with body weight (BW). The significance of correlation persisted after surgery only in males, but disappeared in females. Adipokines were not modified by tumor position, presurgical chemoradiotherapy or surgical technique. Women with RC experiencing weight loss had higher adiponectin than women without weight modifications (p<0.05 at all time points)., Conclusions: Adipokine levels of patients with RC differ from the healthy population, possibly reflecting an adaptation to disease. Adipokine modifications after surgery may be related to acute surgical stress. Whether leptin and adiponectin directly interact is not clear. Women have higher adipokine levels, more so after significant weight loss, but the strength of their correlation with BW decreases after surgery. These data suggest gender differences in the adipokine profile of RC patients which may find clinical applications., Competing Interests: The authors have declared that no competing interests exist.

Background: The coexistence of hyperparathyroidism and thyroid cancer presents important diagnostic and management challenges. With minimally invasive parathyroid surgery trending, preoperative thyroid imaging becomes more important as concomitant thyroid and parathyroid lesions are reported. The aim of the study was to evaluate the rate of thyroid cancer in patients operated for either primary (PHPT) or secondary hyperparathyroidism (SHPT)., Methods: Our retrospective study included PHPT and SHPT patients submitted to parathyroidectomy and, when indicated, concomitant thyroid surgery between 2010 and 2017., Results: Parathyroidectomy was performed in 217 patients: 140 (64.5%) for PHPT and 77 (35.5%) for SHPT. Concomitant thyroid surgery was performed in 75 patients with PHPT (53.6%), and 19 papillary thyroid carcinomas (PTC) were found, accounting for 13.6% from all cases with PHPT and 25.3% from PHPT cases with concomitant thyroid surgery. Thirty-one of operated SHPT patients (40.3%) also underwent thyroid surgery and 9 PTC cases were diagnosed (11.7% of all SHPT patients and 29% of patients with concomitant thyroid surgery). We found differences between PHPT and SHPT patients (p < 0.001) with respect to age (54.6 ± 13y versus 48.8 ± 12y), female-to-male ratio (8:1 versus ~ 1:1), surgical technique (single gland parathyroidectomy in 82.8% PHPT cases; versus subtotal parathyroidectomy in 85.7% SHPT cases) and presurgical PTH (357.51 ± 38.11 pg/ml versus 1020 ± 161.38 pg/ml). Morphopathological particularities, TNM classification and multifocality incidence of PTC were similar in the two groups. All PTC from patients with SHPT were thyroid microcarcinomas (TMC, i.e. tumors with a diameter smaller than 1 cm), whereas seven out of the 19 cases with PTC and PHPT were larger than 1 cm., Conclusions: PTC was frequently and similarly associated with both PHPT and SHPT irrespective of presurgical PTH levels. Thyroid tumors above 1 cm were found only in patients with PHPT. Investigators should focus also on associated thyroid nodular pathology in patients with PHPT.

The process of melanin synthesis and distribution is called melanogenesis, a process that is based on melanocytes present among the basal cells of the epidermis. Pigments formed in melanocyte melanosomes are then stored in the basal layer of epidermal cells, as well as in dermal macrophages, which become melanophores. From the embryological point of view, melanocytes derive from the melanoblasts of the neural crest, from where they migrate during the first months of life into the skin, eye, cochlea, bone, peripheral nervous system, heart and adipose tissue. The melanic pigments, eumelanin and pheomelanin, are the final product of complex biochemical reactions starting from the amino acid L-tyrosine. Melanin has a major role in skin homeostasis through the photoprotection it offers from the harmful effect of ultraviolet radiation. Melanin absorbs and/or reflects ultraviolet radiation but is also involved in the neutralizing process of free radicals and reactive oxygen species. Pigmentogenesis is a dependent oxygen process and is controlled by intrinsic factors (genetic and hormonal) as well as extrinsic factors (ultraviolet radiation). Melanogenesis is stimulated by stimulant melanocytic hormone, adrenocorticotropin hormone, estrogens and progesterone. The present review aimed to provide a summary of recent data about melanogenesis physiology.

Purpose: Fat mass (FM) is a source of adipocytokines, with both positive and negative bone consequences. We aimed to investigate the role of body composition and adipokines as predictive factors for bone mass in women., Methodology: This cross-sectional study included 93 women (38 premenopausal and 55 postmenopausal). Bone mineral density (BMD) and body composition were assessed by dual-energy X-ray absorptiometry. Serum levels of leptin, adiponectin, resistin, and also of the phosphocalcic markers parathormone and vitamin D were measured., Results: Only lean mass (LM) was an independent predictor of BMD in premenopausal women (r 2  = 0.381, p < 0.001 for femoral neck BMD, r 2  = 0.2, p < 0.01 for whole-body BMD) in both unadjusted and age-adjusted models. The effect of total FM upon BMD became nonsignificant when LM was added to the models assessed. In postmenopausal women, although LM, trunk-to-leg fat ratio, and resistin were initially associated with BMD in unadjusted models, only the trunk-to-leg fat ratio independently predicted BMD at various sites (r 2  = 0.171, p < 0.01 for lumbar BMD, r 2  = 0.078, p < 0.05 for radius BMD, r 2  = 0.094, p < 0.05 for whole-body BMD) after adjusting for age., Conclusions: While in premenopausal women the effect of LM upon bone is prevalent, after menopause, the fat distribution reflected by trunk-to-leg fat ratio is a major determinant of bone mass at different sites. Our study also stresses that the relationship between total FM and BMD is not mediated by adipokines in women irrespective of menopausal status and body composition, but it is largely mediated by LM only in young premenopausal women.

Acne is the most common affection of adolescents, although it can be also found in adult women. Our study was aimed at the comparative assessment of three different therapies over a three-month period, applied to women with moderate comedogenic and papulo-pustular endocrine acne. In the study 116 female patients with endocrine localized face acne were included and divided into three groups: group I with 42 patients was treated with a combination of contraceptive pill + local treatment + pulsed-vacuum light; group II with 38 patients was treated with contraceptives and pulsed-vacuum light and group III with 36 patients was treated only with local treatment. The acne evaluation was made using the Global Acne Grading System (GAGS). Statistical data processing was carried out using the STATA software. For the comedogenic form of acne, the good and very good results were superior in group I vs group II and III (83.33% vs 31.58% vs 5.56%) at the end of the three months of treatment. For the papulo-pustulous form of acne, good and very good results were similar in groups I and II (92.86% vs 73.68%) both after the first month of treatment and at the end of the study, well above the local treatment group (13.99%). Our study highlighted the superiority of laser treatment combined with hormonal treatment, compared to hormonal and local treatment in the comedogenic form of acne, and the superiority of hormonal treatment combined (or not) with laser treatment in the papulo-pustular form compared to local treatment.

Cardiovascular disease is one of the main burdens of healthcare systems worldwide. Nevertheless, assessing cardiovascular risk in both apparently healthy individuals and low/high-risk patients remains a difficult issue. Already established biomarkers (e.g. brain natriuretic peptide, troponin) have significantly improved the assessment of major cardiovascular events and diseases but cannot be applied to all patients and in some cases do not provide sufficiently accurate information. In this context, new potential biomarkers that reflect various underlying pathophysiological cardiac and vascular modifications are needed. Also, a multiple biomarker evaluation that shows changes in the cardiovascular state is of interest. This review describes the role of selected markers of vascular inflammation, atherosclerosis, atherothrombosis, endothelial dysfunction and cardiovascular fibrosis in the pathogenesis and prognosis of cardiovascular disease: the potential use of cardiotrophin-1, leptin, adiponectin, resistin and galectin-3 as biomarkers for various cardiovascular conditions is discussed., Competing Interests: The authors declare no conflict of interest.

Plateau iris is characterized by closing the anterior chamber angle due to a large ciliary body or due to its anterior insertion that alters the position of iris periphery in respect to the trabecular meshwork. There are two aspects that need to be differentiated: plateau iris configuration and plateau iris syndrome. The first describes a situation when the iris root is flat and the anterior chamber is not shallow, the latter refers to a post laser iridotomy condition in which a patent iridotomy has removed the relative pupillary block, but goniscopically confirmed angle closure recurs without central shallowing of the anterior chamber. Isolated plateau iris syndrome is rare compared to plateau iris configuration. We hereby present two case reports of plateau iris syndrome in young patients who came to an ophthalmologic consult by chance.

Aim: To evaluate the real incidence of contact dermatitis, to identify the most common allergens, the favoring factors, to establish the prophylaxis methods, the key for a correct management of the patient with contact dermatitis., Method: A retrospective study, on the patients that refers to the Dermatology Clinic, "St. Spiridon" Emergency Hospital Iasi, between 01.01.2006 and 31.12. 2009, based on demographic items, the type of contact dermatitis and the allergens implicated., Results: we enrolled 353 patients between 2006-2009, representing 3,89% from the hospitalized patients; the study reveals a higher incidence at women (60,27%), similar with data from literature; the majority of the patients was aged over 45, with the higher rate in the interval of 45-65 years old; the most frequent implicated allergens and irritants were plants (26,31% - 92 patients) and topical drugs and antiseptics (25,65% - 89 patients); the area most affected was the face (25%) and the hands (19,07%), from which almost 80-90% was occupational dermatitis. The distribution of cases depending on the type of contact dermatitis indicates an approximate percentage of those allergic to those irritant., Conclusions: The real prevalence of this disease is unknown, being frequently a missed diagnosis (other kinds of eczema), the key of the correct diagnose being a repeated, exhaustive anamnesis, revealing all the favoring conditions and possible contact allergens.

The vitamin D analog TX527 (19-nor-14,20-bis epi-23-yne-1,25(OH)(2)D(3)), decreased disease severity (P < 0.001) and postponed disease onset (P < 0.0001) in SJL mice in which experimental autoimmune encephalomyelitis was induced. Levels of IFN-gamma and IL-2 mRNA were decreased in spinal cord and spleen in the analog-treated mice, suggesting a Th(1)-targeted effect. Adding the bisphosphonate pamidronate did not affect analog-protective efficacy, but completely prevented TX527-caused acceleration of bone turnover and increased total bone mineral content as well as femoral mineral and calcium content (P < 0.01). Less calcemic analogs of 1,25-dihydroxyvitamin D(3), in combination with bone sparing products such as bisphosphonates allow immune modulation in vivo without affecting bone.

Background: Most immunosuppressants have a narrow margin between efficacy and side effects. A major goal in the development of immunomodulatory strategies is the discovery of combinations of drugs exerting synergistic immunomodulatory effects. The active form of vitamin D, 1,25(OH)2D3, is an immunomodulator that interacts with T cells but mainly targets antigen-presenting cells. We have demonstrated synergism between 1,25(OH)2D3 and cyclosporine, rapamycin, and FK506. The aim of this study was to investigate whether this synergism could be observed with other immunosuppressants (mycophenolate mofetil, leflunomide, and the methylxanthine A802715) and whether analogs of 1,25(OH)2D3 share this synergistic capacity in vivo., Methods: In vitro, the median effect analysis was applied to the inhibition of phytohemagglutinin A-induced lymphocyte proliferation. In vivo, synergism between analogs of 1,25(OH)2D3 and cyclosporine or mycophenolate mofetil was evaluated in experimental autoimmune encephalomyelitis., Results: In vitro, all combinations with 1,25(OH)2D3 were synergistic. The strongest synergism was seen with the inhibitors of interleukin 2 secretion, cyclosporine and FK506 (indexes 0.16 and 0.27, respectively). The weakest synergism was observed in combinations using A802715, a second-signal inhibitor (index 0.52), or the nucleotide synthesis inhibitor mycophenolate mofetil (index 0.43). In vivo, analogs of 1,25(OH)2D3 share the in vitro-observed synergism with 1,25(OH)2D3. Moreover, the differences in synergism with different immunomodulators were also present in vivo, where the best synergism was again seen in combination with cyclosporine (up to 100% paralysis protection)., Conclusions: These data confirm that 1,25(OH)2D3 and its analogs are potent dose-reducing drugs for other immunomodulators, making them potentially interesting for clinical use in autoimmunity and transplantation.

We investigated the effect on membrane fluidity induced by D-myo-inositol derivatives (IP3, IP4, IP5, IP6). Fluidity was determined as the anisotropy of fluorescence polarisation from liposome model membranes labelled with DPH (1,6-diphenyl-1,3,5 hexatriene). IP3 (10(-10) to 10(-5) M) increased the membrane fluidity with a maximum effect at 10(-5) M. For IP4, IP5 and IP6, at concentrations less than 10(-6) M these derivatives increased the membrane viscosity (i.e. reduced fluidity). This effect was enhanced when the derivatives were incorporated in the vesicles, rather than added to the vesicle suspension. In this case IP5 and IP6 increased viscosity over the reference values. We conclude that inositol derivatives directly modified membrane fluidity which could play a role in their effects in biological systems, beside the one mediated by binding to specific receptors.

The active form of vitamin D, 1 alpha, 25-(OH)2D3, displays immunomodulatory effects in vitro and in vivo at pharmacological levels. We evaluated the dose-effect relationship of 1,25(OH)2D3 and sirolimus (rapamycin, RAP) in vitro, on the inhibition of PHA-stimulated PBMC proliferation, by using the median effect analysis. Pharmacological concentrations of 1,25(OH)2D3 (between 10(-9) and 3 x 10(-6) M) interacted synergistically with RAP (combination index value of 0.01 for 50% suppression of PBMC proliferation). In vivo, the effect of 1,25(OH)2D3 and RAP combinations on the evolution of experimental allergic encephalomyelitis in SJL mice was analyzed. 1,25(OH)2D3, given i.p., in monotherapy, at a dose of 2 micrograms/kg every two days, from day -3 until day +19 after disease induction, or RAP, injected daily at a dose of 0.3 mg/kg for the same period, decreased EAE incidence (paralysis in 70 and 55% of the animals, respectively, versus 98% in the placebo treated group, p < 0.001). The combination treatment using the two drugs in these subtherapeutical doses provided near-total clinical (8% paralysis, p < 0.001 compared to monotherapy with 1,25(OH)2D3 or RAP) and histological protection, comparable to that obtained with RAP in monotherapy at a threefold higher dose (1 mg/kg/d). When the two drugs were given using an alternate day administration schedule (RAP at 0.6 mg/kg and 1,25(OH)2D3 at 2 micrograms/kg, each given on alternate days from day -3 to 19), near total protection was again obtained (13% paralysis, p < 0.001 versus control). These in vitro and in vivo data support the existence of synergistic interactions between 1,25(OH)2D3 and RAP. Considering the narrow therapeutic windows of both RAP and vitamin D-related compounds in autoimmune disease models, combinations of these drugs could find clinical application in reducing their individual therapeutically efficient doses to non-toxic levels.

The effects of brefeldin A, a putative specific agent that disassembles the Golgi apparatus were assessed on the contractility of de-endothelised rat aorta. Brefeldin A inhibited, either as pre- or as post-treatment, the contractions elicited by K+ (75 mM) or phenylephrine (10 microM), being significantly more potent upon the latter. The thapsigargin (1 microM)-induced rat aorta contraction was less sensitive to brefeldin A inhibition. Pre-treatment with brefeldin A (30-100 microM) did not affect phenylephrine-induced transient contractions in Ca2+-free medium, but strongly inhibited the phenylephrine-induced sustained contractions upon re-admission of Ca2+ to the medium. Brefeldin A was unable to prevent Ca2+ stores refilling. We concluded that brefeldin A inhibits Ca2+ entry but not the pathways activated after Ca2+ stores depletion or the pathways responsible for replenishment of these stores in rat aorta, presumably by disassembling the Golgi apparatus network.