Melatonin Membrane Receptors in Peripheral Tissues: Distribution and Functions

Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes

Ultrastructural clues for glutamate-induced necrosis in parietal and cerebellar neurons

Glutamate excitotoxicity has been postulated to underlie the neuronal death that occurs after ischemia. The most sensitive tissues to ischemic injury are hippocampus and cerebellum, whereas cerebrum is more resistant. We studied the glutamate-induced ultrastructural alterations in rat parietal and cerebellar neurons comparatively. We observed that glutamate (45 min, 10(-7) M) causes considerable nuclear, mitochondrial and cytoplasmic changes in both the neuron types. Mitochondrial and nuclear changes were particularly more severe in cerebellar granular, than the ones in parietal neurons. It has been concluded that glutamate induces necrotic changes in both parietal and cerebellar neurons. But cerebellar cortex was found to be more sensitive to glutamate excitotoxicity than cerebral cortex. We suggest that mitochondrial damage is, probably, an important factor in neuron necrosis, which is mediated by glutamate excitotoxicity

Congenital Cutis Laxa Associated with Growth Retardation

Congenital cutis laxa is a rare, clinically and genetically heterogeneous group of inherited disorders. It is characterized by degenerative changes in elastic fibres and manifests with skin laxity. Here we presented a six-month old boy with congenital cutis laxa associated with growth retardation. We reveal ultrastructural findings and discussed the differential diagnosis. "Cutis Laxa Congénita Aociada con Retardo del Crecimiento" RESUMEN El laxa del cutis es un grupo raro, clínica y genéticamente heterogéneo de desórdenes heredados. Esta afección se caracteriza por cambios degenerativos en las fibras elásticas y se manifiesta en la hiperlaxitud de la piel. Aquí presentamos el caso de un niño de seis meses con cutis laxa congénita asociada con retardo del crecimiento. Se revelan los hallazgos ultra-estructurales y se discute el diagnóstico diferencial

Ultrastructural clues for the protective effect of melatonin against oxidative damage in cerulein-induced pancreatitis

The role of oxidative stress has been evaluated in experimental models of acute pancreatitis (AP). The aim of this study is to investigate the effect of melatonin on the ultrastructural changes in cerulein-induced AP in rats. Acute pancreatitis was induced by two i.p. injections of cerulein at 2-hr intervals (50 mu g/kg BW). One group received additionally melatonin (20 mg/kg BW) i.p. before each injection of cerulein. The rats were sacrificed 12 hr after the last injection. Pancreatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides and changes in the antioxidant enzyme levels, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) levels. Ultrastructural examination was performed using a transmission electron microscope. Formation of numerous, large autophagosomes, mitochondrial damage, dilatation of rough endoplasmic reticulum (RER) and Golgi apparatus, margination and clumping of nuclear chromatin were the major ultrastructural alterations observed in the AP group. Melatonin administration prevented mitochondrial and nuclear changes and dilatation of RER and Golgi apparatus. Rare, small autophagosomes were present within the cytoplasm of some of the acinar cells. Pancreatic damage was accompanied by a significant increase in tissue MDA levels (P < 0.05) and a significant decrease in CAT, SOD, GPx activities and GSH levels (P < 0.005). Melatonin administration significantly reduced MDA levels but increased CAT, SOD, GPx activities and GSH levels (P < 0.005). Melatonin also reduced serum amylase and lipase activities, which were significantly elevated in AP (P < 0.05 and P < 0.005 respectively). These results suggest that oxidative injury is important in the pathogenesis of AP. Melatonin is potentially capable of limiting pancreatic damage produced during AP by protecting the fine structure of acinar cells and tissue antioxidant enzyme activities

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 µg/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 ± 2.29, 20.89 ± 10.13, 11.52 ± 4.60, 18.69 ± 8.56, and 8.58 ± 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 ± 0.83, 1.09 ± 0.35, 2.05 ± 0.91, 1.70 ± 0.60, and 2.85 ± 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 ± 0.25, 0.33 ± 0.09, 0.37 ± 0.04, 0.34 ± 0.07 and 0.42 ± 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tissue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage

Serum interleukin-2, interleukin-6, tumour necrosis factor-alpha and nitric oxide levels in patients with Behcet's disease

Introduction: Behcet's disease (BD) is a chronic systemic disorder characterised by oral and genital ulcerative lesions, ocular and cutaneous manifestations. Cytokines are the major mediators of immunologic and inflammatory reactions. Nitric oxide is reactive nitrogen intermediate which plays a key role in pathogenesis of many inflammatory and autoimmune skin diseases. The study was conducted to determine serum interleukin-2 (IL-2), interleukin-6 (IL-6), tumour necrosis factor (TNF)-alpha and nitric oxide levels in relation to the pathogenesis of Behcet's disease. Materials and Methods: Serum IL-2, IL-6, and TNF-alpha levels were measured with test kits by enzyme-linked immunosorbent assay (ELISA) method, while serum nitric oxide levels were determined with a test kit by colorimetric method. Serum IL-2, IL-6, TNF-alpha and nitric oxide concentrations in 27 patients with Behcet's disease and in 16 healthy controls were determined by extrapolation from their standard curves. The significance of the mean differences between the 2 groups was assessed by the Mann-Whitney U test. Results: The serum levels of IL-2, IL-6, TNF-alpha, and nitric oxide concentrations in patients with BD were significantly higher than those of the controls (P < 0.001). Conclusion: Our results suggest that elevated levels of IL-2, IL-6, TNF-alpha, and nitric oxide in Behcet's disease appear to be related to the disease