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Purpose: The aim of this study was to assess the effect of local application of growth hormone on osseointegration of dental implants inserted in osteoporotic bones. Materials and Methods: Twenty female New Zealand rabbits were used in this study. Ten were ovariectomized and fed a low-calcium diet for 6 weeks, and the others remained intact. A titanium implant was inserted into each tibia, in both groups. In half of the rabbits, 2 IU of growth hormone was placed into the ostectomy prior to the implant insertion. Two weeks after implant surgery, all animals were sacrificed. Tibiae were dissected from soft tissues, and included in methacrylate to be studied under light microscopy. Bone-to-implant contact (BIC) and bone mineral density (BMD) were measured by morphometric and densitometric analysis, respectively. Multifactorial analysis of variance (ANOVA) was used for statistical evaluation. P < .05 was considered to be significant. Results: Ovariectomy induced less BIC and BMD in regions closer to the implant compared with the control group. Local application of growth hormone was able to increase the BIC in the ovariectomized group, with statistically significant differences with respect to the control group (P < .01). Regarding the BMD, no statistically significant differences were found. Conclusion: Within the limitations of this experimental study, local application of 2 IU of recombinant human growth hormone at the moment of titanium implant insertion in rabbit tibiae significantly enhanced the BIC around titanium implants 15 days after the implantation in this experimental osteoporotic animal model, without affecting the BMD. [ABSTRACT FROM AUTHOR]

Purpose: The achievement of primary stability in porous and soft bone, where implants are more likely to fail, is one of the unresolved challenges of implant dentistry. Therefore, the aim of the study was to validate an osteoporotic animal model for analysis of poor-quality bone. Materials and Methods: Sixteen female New Zealand rabbits, each 6 months old and weighing 4 to 5 kg, were used in this study. The animals were anesthetized, and an in vivo densitometric analysis was performed by dual-energy x-ray absorptiometry (DEXA) to measure bone mineral density (BMD) in the calvaria, cervical spine, and tibia. Ovariectomy was then performed, and animals were fed a low-calcium diet that featured 0.07% calcium, rather than the 0.45% calcium of a standard diet, for 6 weeks. After this period, new densitometric measurements were carried out. Two-way analysis of variance was used for statistical evaluation. A P value of less than .05 was considered to be significant. Results: Together, ovariectomy and a low-calcium diet were able to induce a quick decrease in BMD, as measured at 6 weeks by DEXA. This decrease was statistically significant in the calvaria (P < .001) and the cervical spine (P < .05) but not in the tibia. Conclusion: Based upon this study, ovariectomy and a low-calcium diet are able to induce experimental osteoporosis in rabbits in a short period of time. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate the qualitative and quantitative differences that could appear in newly formed peri-implant bone around Screw-Vent implants placed in rabbit tibiae when treated with local administration of growth hormone (GH). Materials and Methods: Eight New Zealand rabbits were randomly divided into 2 groups: the experimental group, which received 4 IU of GH in the form of lyophilized powder added to the ostectomy site before implant placement, and the control group, which did not receive GH before implant placement. Animals were sacrificed 2 weeks later, and histologic sections were obtained for histomorphometry and observation under light microscopy. Results: The sections in the GH-treated group presented enhanced growth of new trabeculae from the periosteal tissue, and the bone-to-implant contact in the experimental group was significantly greater (P < .05). Discussion: Local administration of GH stimulated a more dramatic effect than that seen previously with systemic GH administration, prompting growth from both the periosteum and endosteum. Conclusions: Local administration of GH at the time of implant placement could enhance peri-implant bone reaction. [ABSTRACT FROM AUTHOR]

Aging is associated with an increase in stroke risk. Melatonin, a potent free radical scavenger and broad spectrum antioxidant, has been shown to counteract inflammation and apoptosis in brain injury. However, little is known on the possible protective effects of melatonin in aged individuals affected by brain ischemia. Also, using melatonin before or after an ischemic stroke may result in significantly different molecular outcomes. The objective of the present study was to compare the effects of pre-ischemia vs. post-ischemia melatonin administration in an ischemic lesion in the cortex and hippocampus of senescent Wistar rats. An obstruction of the middle cerebral artery (MCA) to 18-month-old animals was performed. In general, animals treated with melatonin from 24 h prior to surgery until 7 days after the surgical procedure (PrevT) experienced a significant decrease in the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), glial fibrillary acidic protein (GFAP), Bcl-2-associated death promoter (BAD), and Bcl-2-associated X protein (BAX) in both cortex and hippocampus, while hippocampal levels of sirtuin 1 (SIRT1) and B-cell lymphoma 2 (Bcl-2) increased. Treatment of animals with melatonin only after surgery (AT) resulted in similar effects, but to a lesser extent than in the PrevT group. In any case, melatonin acted as a valuable therapeutic agent protecting aged animals from the harmful effects of cerebral infarction. [ABSTRACT FROM AUTHOR]

An abstract of the research paper "Brain, aging, and melatonin: Evidence of neuroprotection against experimental ischemic injury" by Sergio D. Paredes and colleagues that was presented in the conference 1st International Brain Research School held in August-September 2015, is presented.

Background: Recently published data suggest that showing patients operated on for adolescent idiopathic scoliosis or kyphosis their preoperative and postoperative photographs may enhance their satisfaction and self-image as measured by Scoliosis Research Society Health-Related Quality of Life Questionnaire (SRS-22) scores. No data exist for adult spinal deformity (ASD) surgery. The aim of this study is to determine the effect on patient postoperative satisfaction and self-image of showing adult deformity patients their preoperative and postoperative whole body photographs., Methods: This was a nonconcurrent prospective study. Patients operated on for ASD with a minimum 2-year postoperative follow-up who had preoperative full-body photographs taken by a professional photographer were included. Two follow-up visits were arranged 7 days apart. In the first visit, patients completed the SRS-22 questionnaire, and full-body standing photographs were taken. In the second visit, patients were asked to complete again questions 4, 6, 10, 14, 19 (self-image), 21, and 22 (satisfaction) of the SRS-22 after seeing their preoperative and postoperative full-body photographs., Results: Thirty patients (28 female) were included. The median age at surgery was 50 years (26-76). The median follow-up was 51 months (24-120). SRS-22 results at first visit were: activity 2.79 ± 0.75; self-image 2.71 ± 0.82; pain 2.53 ± 1.10; mental health 3.08 ± 0.77; satisfaction 3.46 ± 1.20; global 2.74 ± 0.72. SRS22 results at second visit were: self-image 2.9 ± 0.75; satisfaction 4.02 ± 0.97. After seeing the preoperative and final follow-up photographs, patients experienced an improvement in SRS-22 self-image ( P = .000) and satisfaction domains ( P = .011)., Conclusions: In patients operated on for ASD, showing preoperative and postoperative photographs improves patient satisfaction with surgery and self-image., Level of Evidence: 3., Clinical Relevance: Our results could be a starting point for introducing full-body clinical photographs as a routine clinical tool in adult deformity patients undergoing surgery., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2020 ISASS.)

Aging induces changes in bone. Growth hormone (GH) is reduced by aging, and age-related changes observed in old bones might be due to a decrease in the GH/insulin-like growth factor-I (IGF-I) axis. GH administration on aged individuals is controversial. This study aimed to assess the effect of systemic GH treatment on bone properties, bone metabolism, and bone mineral density (BMD) in long bone of old rats. Aged Wistar rats were treated with GH at a dose of 2 mg/kg/day during 10 weeks. Plasma osteocalcin, IGF-I, and carboxy-terminal telopeptide of type I collagen levels were measured. Cross-sectional bone areas and BMD were measured by morphometric and densitometric analysis, respectively. Femora were analyzed by three point-bending testing. t -Test was used for statistical evaluation. p  < 0.05 was considered to be significant. Significantly enhanced bone area, at the expense of the cortical area, was found in treated rats. The densitometric analysis showed 11% higher BMD in the experimental group. Significantly higher bone flexural modulus, stiffness, and ultimate load were observed in the treated rats. Plasma osteocalcin and IGF-I levels were significantly increased in the treated group, while the resorption marker concentration remained unchanged. Within the limitations of this experimental study, systemic GH administration has shown to enhance biomechanical properties, BMD, cortical mass, and plasma IGF-I and osteocalcin in old treated rats, compared to the control group; consequently, GH could be considered as an alternative therapy against age-related changes in the bone.

Study Design: This is nonconcurrent prospective study approved by the Institutional Research Ethics Committee., Objective: The purpose of this study is to determine if the cranial sagittal vertical axis (Cr-SVA) measured in full spine standing radiographs is a better predictor of clinical results than the C7 sagittal vertical axis (C7-SVA) in adult patients operated on spinal deformity with a minimum 2-year follow-up after surgery., Summary of Background Data: The Cr-SVA has recently been described as a better predictor of health-related quality of life outcomes than the C7-SVA for patients with adult spinal deformity (ASD) before undergoing surgery. This has not been confirmed in patients after ASD surgery., Methods: Inclusion criteria were age at surgery more than 25 years and a minimum 2-year follow-up after a ≥5 level fusion for ASD. Full-length standing lateral radiographs (including nasion-inion line, spine, and femoral heads) and Scoliosis Research Society 22 Questionnaire and SF36 questionnaires were available for every patient at the final follow-up. The distance from the Cr-SVA to the posterior corner of S1 (Cr-SVA-S) and to the centers of the hip (Cr-SVA-H) was measured and also the C7-SVA, lumbar lordosis, pelvic incidence, pelvic tilt, and PI-LL., Results: Sixty-five patients (58 female individuals) operated on ASD in a single institution were included. Age at surgery was 61 years (26-67). The mean follow-up was 53 months (24-120). Spearman rank-order test showed several significant correlations. After multivariable analysis, only Cr-SVA-S and age persisted as predictors for Scoliosis Research Society (SRS) image scores, Cr-SVA-H for SRS satisfaction, Cr-SVA-H and age for SRS total scores, Cr-SVA-H and age for SF36 Physical Function, Cr-SVA-S for SF36 Role Physical, Cr-SVA-H for SF36 Bodily Pain, and Cr-SVA-H for SF36 Role Emotional., Conclusions: The Cr-SVA measured in full spine standing radiographs seems to be a better predictor of health-related quality of life outcomes than the C7-SVA for adults operated on spinal deformity >2 years after surgery., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

It has been recently shown that xanthohumol, a flavonoid present in hops, possesses antioxidant, anti-inflammatory and chemopreventive properties. However, its role in the aging brain has not been addressed so far. Therefore, this study aimed to investigate the possible neuroprotective activity of xanthohumol against age-related inflammatory and apoptotic brain damage in male senescence-accelerated prone mice (SAMP8). Animals were divided into 4 groups: Untreated young mice, untreated old mice and old mice treated either with 1 mg kg -1 day -1 or 5 mg kg -1 day -1 xanthohumol. Young and old senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed and their brains were collected and immediately frozen in liquid nitrogen. mRNA (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, XIAP, NAIP and Bcl-2) and protein (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, BDNF, synaptophysin and synapsin) expressions were measured by RT-PCR and Western blotting, respectively. Significant increased levels of pro-inflammatory (TNF-α, IL-1β) and pro-apoptotic (AIF, BAD, BAX) markers were observed in both SAMP8 and SAMR1 old mice compared to young animals (P<.05) and also in SAMP8 untreated old mice compared to SAMR1 (P<.05). These alterations were significantly less evident in animals treated with both doses of xanthohumol (P<.05). Also, a reduced expression of synaptic markers was observed in old mice compared to young ones (P<.05) but it significantly recovered with 5 mg kg -1 day -1 xanthohumol treatment (P<.05). In conclusion, xanthohumol treatment modulated the inflammation and apoptosis of aged brains, exerting a protective effect on damage induced by aging., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aging is a physiological state in which a progressive decline in organ functions is accompanied by the development of age-related diseases. Resveratrol supplementation has been shown to exert anti-inflammatory and antioxidant effects in various mammalian models of aging. Senescence-accelerated mice (SAM) are commonly used as animal models to investigate the aging process. In the present study, the effects of inflammation, oxidative stress and apoptosis in pancreas of two different types of SAM (SAMR1 or resistant to aging, and SAMP8 or prone to aging) have been analysed, as well as the effect of resveratrol administration (5mg/kg/day) on these parameters in the SAMP8 strain. mRNA expressions of sirtuin 1 and FoxO factors were found to be decreased with aging in SAMP8 mice. An increase in inflammatory status and nuclear-factor kappa B (NFκB) protein expression was also observed in old mice, together with a decrease of anti-apoptotic markers and antioxidant-enzyme activity. Resveratrol administration was able to increase sirtuin 1 mRNA expression, as well as decreasing NFκB expression and reducing the proinflammatory and prooxidant status associated with age. In conclusion, resveratrol was able to modulate the inflammatory, oxidative and apoptotic status related to aging, thereby exerting a protective effect on pancreas age-induced damage., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aging is associated with an increase in oxidative stress and inflammation. The aging lung is particularly affected since it is continuously exposed to environmental oxidants while antioxidant machinery weakens with age. Melatonin, a free radical scavenger, counteracts inflammation and apoptosis in healthy cells from several tissues. Its effects on the aging lung are, however, not yet fully understood. This study aimed to investigate the effect of chronic administration of melatonin on the expression of inflammation markers (TNF-α, IL-1β, NFκB2, HO-1) and apoptosis parameters (BAD, BAX, AIF) in the lung tissue of male senescence-accelerated prone mice (SAMP8). In addition, RNA oxidative damage, as the formation of 8-hydroxyguanosine (8-OHG), was also evaluated. Young and old animals, aged 2 and 10 months respectively, were divided into 4 groups: untreated young, untreated old, old mice treated with 1mg/kg/day melatonin, and old animals treated with 10mg/kg/day melatonin. Untreated young and old male senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed. Lungs were collected and immediately frozen in liquid nitrogen. mRNA and protein expressions were measured by RT-PCR and Western blotting, respectively. Levels of 8-OHG were quantified by ELISA. Mean values were analyzed using ANOVA. Old nontreated SAMP8 animals showed increased (p<0.05) mRNA and protein levels of TNF-α, IL-1β, NFκB2, and HO-1 compared to young mice and SAMR1 mice. Melatonin treatment with either dose reversed the aging-derived inflammation (p<0.05). BAD, BAX and AIF expressions also rose with aging, the effect being counteracted with melatonin (p<0.05). Aging also caused a significant elevation (p<0.05) in SAMP8 8-OHG values. This increase was not observed in animals treated with melatonin (p<0.05). In conclusion, melatonin treatment was able to modulate the inflammatory and apoptosis status of the aging lungs, exerting a protective effect on age-induced damage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription-polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury.

Introduction: Previous studies have indicated that resveratrol, a natural phytoestrogen, can act as an anti-aging therapy to resist age-related changes of several body tissues. However, the anti-aging effects of resveratrol on bone have been poorly investigated in this natural aging population. Accordingly, this study was design to evaluate the effects of resveratrol on bone mass and biomechanical properties in old rat femora., Methods: Twenty 22-month-old male Wistar rats were divided into two randomly assigned groups (n=10). The first group was treated for 10 weeks with resveratrol (10 mg/kg per day) and the second group was left untreated (control). Rat femora were collected. Bone mass and bone microestructure were investigated by microcomputed tomography and histomorphometry. Biomechanical properties were determined by a three-point bending test. Plasma levels of CTX (carboxy-terminal telopeptide of type I collagen) and osteocalcin were also determined. Statistical analyses were performed by a Student two-tailed unpaired t-test. In all experiments, a value of p<0.05 was considered significant., Results: Microcomputed tomography analyses demonstrated that resveratrol-treated rats had significant higher bone volume, bone trabecular number, and cortical thickness and lower spacing between trabeculae in comparison to the control group. Histomorphometric analyses confirmed the increase of bone volume in resveratrol-treated rats compared to controls. Resveratrol-treated rats had significant higher bone flexural modulus, stiffness, and ultimate load compared to control group. Treatment was not associated with changes in plasma CTX or osteocalcin., Conclusion: These findings demonstrate that resveratrol increases bone microstructure and bone mechanical properties in old male rats, suggesting that resveratrol might be used as anti-aging therapy to resist age-induced bone loss.

Introduction: Previous studies have shown that melatonin, an anti-oxidant molecule secreted from the pineal gland, is a positive regulator of bone mass. However, the potential effects of melatonin on bone mass have never been investigated in an old population. The aim of this study was to assess the effects of dietary melatonin supplementation on mass accrual and biomechanical properties of old rat femora., Methods: Twenty 22-month-old male Wistar rats were divided into two randomly assigned groups. The first group was treated for 10 weeks with melatonin, whereas the second group was untreated (control). Rat femurs were collected, and their phenotypes and biomechanical properties were investigated by micro-computed tomography, histomorphometry, and a three-point-bending test. Statistical analyses were performed by the Student two-tailed unpaired t-test. In all experiments, a value of p<0.05 was considered significant., Results: Rats treated with melatonin had higher bone volume, bone trabecular number, trabecular thickness, and cortical thickness in comparison to the control group. Histomorphometric analyses confirmed the increase of bone volume in melatonin-treated rats. In agreement with these findings, melatonin-treated rats showed higher bone stiffness, flexural modulus, and ultimate load compared to controls., Conclusion: These compelling results are the first evidence indicating that dietary melatonin supplementation is able to exert beneficial effects against age-related bone loss in old rats, improving the microstructure and biomechanical properties of aged bones.

Epidemiological studies indicate that certain aspects of lifestyle and genetics act as risk factors for a variety of cardiovascular disorders, including coronary disease, hypertension, heart failure and stroke. Aging, however, appears to be the major contributor for morbidity and mortality of the impaired cardiovascular system. Growth hormone (GH) and melatonin seem to prevent cardiac aging, as they contribute to the recovery of several physiological parameters affected by age. These hormones exhibit antioxidant properties and decrease oxidative stress and apoptosis. This paper summarizes a set of studies related to the potential role that therapy with GH and melatonin may play in the protection of the altered cardiac function due to aging, with a focus on experiments performed in our laboratory using the senescence-accelerated mouse as an aging model. In general, we observed significantly increased inflammation, oxidative stress and apoptosis markers in hearts from senescence-accelerated prone 10-month-old animals compared to 2-month-old controls, while anti-inflammatory and antiapoptotic markers as well as endothelial nitric oxide synthase were decreased. Senescence-accelerated resistant animals showed no significant changes with age. GH or melatonin treatment prevented the age-dependent cardiac alterations observed in the senescence-accelerated prone group. Combined administration of GH plus melatonin reduced the age-related changes in senescence-accelerated prone hearts in an additive fashion that was different to that displayed when administered alone. GH and melatonin may be potential agents for counteracting oxidative stress, apoptosis and inflammation in the aging heart.

Purpose: The aim of this study was to assess the effect of local melatonin administration on bone osseointegration around implants in rabbit tibiae., Material and Methods: Ten female, 6-month-old New Zealand rabbits were randomly divided into two groups: the experimental group, where five rabbits were treated with local application of melatonin (3 mg) to implant sites when placed into the rabbit tibia, and the control group, those who where without additive materials. Four weeks later, animals were sacrificed; tibiae were dissected from soft tissues and fixed in buffered formaldehyde, and then included in methacrylate. Histological sections were performed to be studied under light microscopy and analyzed morphometrically to evaluate the amount of bone to implant contact (BIC), trabecular area density, and cortical area density. One-way analysis of variance test was used for statistical evaluation. p < .05 was considered to be significant., Results: Histological evaluation showed more trabecular reaction in the melatonin group. Morphometrical analysis showed a statistically significant increase in trabecular BIC in the melatonin group when compared with the control group (24.61% ± 2.87 vs 13.62% ± 1.44; p < .01). Cortical BIC was decreased in the melatonin group, without statistical significance (71.08 ± 3.63 vs 76.28 ± 2.57; p = 0.31). Trabecular area density was increased significantly in the melatonin group (8.68 ± 1.61 vs 4.02 ± 0.36; p < .05). Cortical area density was decreased significantly in the melatonin group (91.31 ± 1.6 vs 95.7 ± 0.5; p < .05)., Conclusion: Within the limitation of this animal study, local melatonin application at the time of implant placement might induce more trabecular bone at implant contact and higher trabecular area density., (© 2010 Wiley Periodicals, Inc.)

This study has investigated the effect of aging on parameters of inflammation, oxidative stress and apoptosis in pancreas obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and resistant mice (SAMR1). Animals of 2 (young) and 10 months of age (old) were used (n = 64). The influence of the administration of melatonin in the drinking water for one month at two different dosages (1 and 10mg/(kg day) on old SAMP8 mice on these parameters was also studied. SAMP8 mice showed with age a significant increase in the relative expression of pancreatic genes involved in inflammation, oxidative stress and apoptosis. Furthermore the protein expression of several NFκB subunits was also enhanced. On the contrary aged SAMR1 mice did not show significant increases in these parameters. Melatonin administration to SAMP8 mice was able to reduce these age related alterations at the two used dosages., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Aging is associated with an increase in inflammation, oxidative stress, and apoptosis. Furthermore, aging is accompanied by an alteration of the growth hormone (GH) -insulin-like growth factor-1 (IGF-1) axis. The aim of this study was to examine the regulation of these parameters in the pancreas of old mice and how GH treatment could affect this process. Male senescence-accelerated prone mice (SAMP8) and male senescence-accelerated resistant mice (SAMR1) 2 (young) and 10 months old were used (n = 40). Animals were divided into five experimental groups: 1 and 2, SAMP8/R1 young control; 3 and 4, SAMP8/R1 old control (untreated); and 5, SAMP8 old treated with GH. Physiologically equivalent doses of GH were administered for 1 month (2 mg subcutaneously [s.c.]/kg/day) and several parameters were analyzed. Aging was associated with increased inflammation, oxidative stress, and apoptosis (increased tumor necrosis factor-α [TNF-α], interleukin-β [IL-β], IL-6, monocyte chemoattractant protein-1 [MCP1], IL-2, heme oxygenase [HO-1], inducible nitric oxide synthase [iNOS], and nitric oxide metabolites [NOx]). The ratio of anti/pro apoptotic mRNA expression-B cell lymphoma 2 (Bcl-2) Bcl-2-associated X protein (BAX) + Bcl-xL/Bcl-2-associated death promoter (BAD)-was decreased during aging in SAMP8 mice. X-inhibitor of apoptosis (XIAP) was decreased during the aging process. Furthermore, no changes were observed in protein expression of nuclear factor-κB (NF-κB p65 and NF-κBp50-105. However, the protein expression of NF-κB p52-100 and inhibitor kappa B (IκB) alpha was increased with age in the pancreas of SAMP8 mice. On the other hand, the expression of IκB beta was decreased with aging. These results indicate that aging is associated with significant alterations in the relative expression of pancreatic genes involved in inflammation, oxidative stress, and apoptosis. According to our results, GH administration to old SAMP8 mice was able to improve pancreas from this parameters.

Objective: The aim of the present study was to investigate the effect of aging on several parameters related to glucose metabolism, proliferation and differentiation in the pancreas and how GH administration to old SAMP8 mice could affect these parameters., Materials and Methods: Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant (SAMR1) mice SAMP8 and SAMR1 mice and the influence of exogenous administration of GH (2mgs.c./kg/day) on SAMP8 mice. RNA was isolated from pancreas samples of male mice using the kit RNeasy total RNA kit Ref. 50974104 (Qiagen). Insulin was measured in plasma by RIA kit and glucose was measured in plasma by an assay kit., Results: Aging decreases the expression of differentiation in the pancreas of Pdx-1, FoxO 1 and FoxO 3A but not of Sirt 1 or of the expression of the proliferative genes PCNA and Sei1. The expression of glucagon and GLUT2 were increased with aging and no differences were observed in somatostatin and insulin expressions. Insulin levels in plasma were increased with aging in SAMP8 mice. IGF-1 expression was reduced with aging. The treatment with GH was able to increase the expression of Sirt 1, Pdx-1, FoxO 3A and IGF-1. On the other hand, the treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin, furthermore GH was able to decrease the plasma levels of insulin in old male SAMP8 mice (p<0.0004)., Conclusion: The present study has shown that aging is associated with significant alterations in the relative expression of pancreatic genes involved in insulin secretion as well as in the differentiation and in the intra islet glucose metabolism. According to our results, GH administration to old SAMP8 mice was able to improve the pancreatic function of the old SAMP8 mice and to decrease insulin and glucagon expressions in the pancreas improving instead insulin levels and glucose metabolism., (Copyright © 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.)

Aging is associated with an increase in oxidative stress and inflammation. The aim of this study was to investigate the effect of aging on various physiological parameters related to inflammation in livers obtained from two types of male mice models: Senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant (SAMR1) mice, and to study the influence of the administration of melatonin (1mg/kg/day) for one month on old SAMP8 mice on these parameters. The parameters studied have been the mRNA expression of TNF-α, iNOS, IL-1β, HO-1, HO-2, MCP1, NFkB1, NFkB2, NFkB protein or NKAP and IL-10. All have been measured by real-time reverse transcription polymerase chain reaction RT-PCR. Furthermore we analyzed the protein expression of TNF-α, iNOS, IL-1β, HO-1, HO-2, and IL-10 by Western-blot. Aging increased oxidative stress and inflammation especially in the liver of SAMP8 mice. Treatment with melatonin decreased the mRNA expression of TNF-α, IL-1β, HO (HO-1 and HO-2), iNOS, MCP1, NFκB1, NFκB2 and NKAP in old male mice. The protein expression of TNF-α, IL-1β was also decreased and IL-10 increased with melatonin treatment and no significant differences were observed in the rest of parameters analyzed. The present study showed that aging was related to inflammation in livers obtained from old male senescence prone mice (SAMP8) and old male senescence resistant mice (SAMR1) being the alterations more evident in the former. Exogenous administration of melatonin was able to reduce inflammation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

An age-related decline in cognitive functions and physical performance has been associated with reductions in growth hormone (GH) secretion and brain neurotransmitter function. In vivo experiments were performed to study the long-term effects of exogenously administered GH on the central monoaminergic neurotransmitters serotonin, dopamine, and noradrenaline and behavioral tests in old Wistar rats. The accumulation of 5-hydroxytryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a measure of the rate of tryptophan and tyrosine hydroxylation in vivo. Also, the content of the neurotransmitters serotonin, dopamine, and noradrenaline and some metabolites was measured by high-pressure liquid chromatography (HPLC) in the hippocampus and striatum, brain regions involved in adult memory processing and motor coordination. The age-related decline observed in all the neurochemical parameters in control rats was significantly reversed after repeated subcutaneous administration of GH (2 mg/kg per day, 4 weeks). Thus, GH treatment exerted a long-term effect on serotonin, dopamine, and noradrenaline neurotransmission by enhancing neurotransmitter synthesis and metabolism in aged rats. The results obtained after examining working memory tasks in the eight-radial maze and motor ability in the Rotarod treadmill in aged rats were consistent with these neurochemical data; both tests were significantly improved after chronic GH treatment. Overall, these in vivo findings suggest that the positive effects induced by GH on serotonin, dopamine, and noradrenaline neurotransmitters might explain, at least in part, the effects of chronic GH treatment in improving cognitive and motor ability in aged rats, and could aid in preventing or delaying deficits in monoamines associated with learning or motor disabilities.

Previous data from our group have provided support for the role of GH, melatonin and estrogens in the prevention of aging of several physiological parameters from bone, liver metabolism, vascular activity, the central nervous system (CNS), the immune system and the skin. In the present work data on the molecular mechanisms involved are presented. A total of 140 male and female rats have been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and melatonin and the second with the two latter compounds and additionally with estradiol and Phytosoya. Aging was associated with a reduction in the number of neurons of the hylus of the dentate gyrus of the hippocampus and with a reduction of neurogenesis. GH treatment increased the number of neurons but did not increase neurogenesis thus suggesting a reduction of apoptosis. This was supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates together with an increase in sirtuin2 and a reduction of caspases 9 and 3. Melatonin, estrogen and Phytosoya treatments increased neurogenesis but did not enhance the total number of neurons. Aging induced a significant increase in mitochondrial nitric oxide in the hepatocytes, together with a reduction in the mitochondrial fraction content in cytochrome C and an increase of this compound in the cytosolic fraction. Reductions of glutathione peroxidase and glutathione S-transferase were also detected, thus indicating oxidative stress and possibly apoptosis. Treatment for 2.5 months of old rats with GH and melatonin were able to significantly and favourably affect age-induced deteriorations, thus reducing oxidative damage. Keratinocytes obtained from old rats in primary culture showed an increase in lipoperoxides, caspases 8 and 3 as well as a reduction in Bcl2 leading to enhanced number of nucleosomes that was also restored upon treatments with GH and melatonin. In conclusion, GH and melatonin treatment seem to have beneficial effects against age-induced damage in the CNS the liver and the skin through molecular mechanisms reducing oxidative stress and apoptosis.

Introduction: Age-related changes in the communication between the neuroendocrine and the immune system have been scarcely studied. Aging in mammals is associated with an impairment of the immune response, especially regarding lymphocyte functions. Furthermore, the endocrine system is also affected by aging, one of the most significant changes being the decrease in the secretion of several hormones such as growth hormone (GH)., Objective: The aim of the present work was to study whether GH replacement therapy in old male rats could improve several lymphocyte functions., Methods: Spleen and axillary node lymphocytes from old (24 months of age) male Wistar rats were used in the present study to investigate the effect of GH (2 mg/kg daily during 10 weeks) on chemotaxis, lymphoproliferative response to the mitogen concanavalin A, interleukin 2 release and natural killer cell activity., Results: We have found that the administration of GH can reduce or even reverse the age-related changes observed in these key immune function parameters. Moreover, we have observed that the recovery of such immune functions is able to reach similar values as those exhibited by young control animals of 6 months of age., Conclusion: Considering that the immune system is a marker of health and a predictor of longevity, hormone replacement therapies with GH, by increasing the immune function and thus delaying or slowing down some aspects of the aging process, could facilitate successful aging., (Copyright 2008 S. Karger AG, Basel.)

Purpose: The objective of this study was to evaluate whether the local administration of growth hormone (GH) would influence the formation of peri-implant bone around titanium sheets placed in the tibiae of young rabbits., Materials and Methods: Thirty-two New Zealand rabbits were randomly placed in 1 of 2 groups: the experimental group, in which 4 IU (1.2 mg) of lyophilized powder (GH) was added to a surgically created defect at implant placement, or the control group, in which an implant sheet was placed without hormonal treatment. Animals were sacrificed at 1, 2, 3, and 6 weeks after surgery, and histologic sections were stained with Masson, Alcian blue, picrosirius, and hematoxylin-eosin and observed under light microscopy. The sections were analyzed morphometrically and densitometrically to calculate the amount of newly formed bone., Results: At week 2, GH-group sections showed enhanced growth of the trabeculae from the periosteal tissue, with thicker and more irregular trabeculae than those observed in control group specimens. A tendency toward greater bone area and lesser density was observed in the GH group, although the groups did not differ significantly. Nevertheless, bone-to-implant contact in weeks 2 and 6 was significantly greater in the GH group (P < .05)., Discussion: An increase in the cortical response from periosteal and endosteal reactions was observed with the high local administration of GH, in disagreement with most authors. In the first phases of bone repair, the osteons were more disorganized; they were more organized by the sixth week., Conclusion: Local administration of GH could stimulate the first phases of the bone remodeling process in this experimental model.

Unlabelled: To investigate the influence of dibutyl phtalate (DBP) given in a soy-free rat chow on pre-pubertal development, 46 Long Evans female rats 2-month-old were divided into three experimental groups and fed three different chows: (1) control; (2) DP 0.61 g/kg chow (12 mg/kgrat/day); (3) DP 2.5 g/kg chow (50 mg/kg rat/day) for 2 months. While under this treatment, they were mated and their offspring studied. Litter size and female:male ratio were recorded. At 14 days of age 6, male pups of each group were sacrificed and testis and thymus were excised and weighed. Pups were weaned at 22 days of age and continued into three experimental groups according to diet. From day 22 onwards, vaginal opening, occurrence of first estrous, and pre-putial separation were recorded., Results: The percent of pregnancies showed a marked decrease in group 3, while no difference was observed between groups 1 and 2. Sex prevalence and litter size were not affected by the different diets. Pup survival showed a decrease when mothers were fed diet 2, but it was similar in diets 1 and 3. Pup weights on day 2 showed an evident (P < 0.05) reduction in groups 2 and 3, the decrease being more marked (P < 0.001) in group 3. On day 6, pups of group 2 showed lower weights (P < 0.01) as compared with the other groups. Weight gain was significantly higher in pups of group 3. Eye opening was not affected by the different diets. Fourteen-day-old male pups' relative weight of thymus and testis showed a decrease in animals whose mothers had been fed diets 2 and 3. Vaginal opening and occurrence of first estrous showed an evident delay (P < 0.05; P < 0.01) in females fed diets 2 and 3. Significant differences (P < 0.001) in pre-putial separation were observed between treated and untreated groups., Conclusion: Offspring pre-pubertal development seems to be affected by oral intake of DBP by their mothers during pregnancy, the effects being more evident in the reproductive development of male pups.

In a first experiment, embryo viability was estimated after recovery in the uterus or the oviduct of 70 Manchega ewes following a treatment of superovulation with decreasing doses of OVAGEN. Fewer viable embryos (5.6 +/- 0.9 vs. 8.3 +/- 0.8, P < 0.05) and more degenerative embryos (31.3% vs. 6.8%, P < 0.005) were obtained from the uterus than from the oviduct respectively. In a second experiment performed on 14 ewes, embryo viability was analyzed in relation to the follicular population estimated by ultrasonography (follicles > or = 2 mm) at the first FSH administration. Progesterone (P4) and oestradiol 17beta (E2) concentrations were also determined from the beginning of the superovulation treatment to the recovery of the embryos. The number of viable embryos (4.3 +/- 1.4) was positively correlated (r = 0.824) with of 2-4 mm diameter follicles (P < 0.05), and with E2 concentrations at -12 h (r = 0.891, P < 0.01) , 0 h (r = 0.943, P < 0.0001) and +24 h (r = 0.948, P < 0.05) from estrus detection. Prolonged high levels of E2 up to 72 h with low levels of P4 on days 3 and 4 after estrus had a negative (P < 0.05) effect on embryo viability. These results indicate that ovarian response to superovulatory protocols is related to the individual variations in the number of follicles of 2-4 mm at the start of FSH treatment, and that embryo viability is conditioned by the steroid patterns during the time spent in the genital tract of the super-ovulated ewes.