Evaluation of skeletal muscle function in male rats with doxorubicin-induced myopathy following various exercise techniques: the significant role of glucose transporter 4.

A common anthracycline antibiotic used to treat cancer patients is doxorubicin (DOX). One of the effects of DOX therapy is skeletal muscle fatigue. Our goal in this research was to study the beneficial effect of exercise on DOX-induced damaged muscle fibers and compare the effect of different exercise strategies (prophylactic, post- toxicity and combined) on DOX toxicity. Five groups were created from 40 male rats: group I, control group; group II, DOX was administered intraperitoneally for 2 weeks over 6 equal injections (each 2.5 mg/kg); group III, rats trained for 3 weeks before DOX; group IV, rats trained for 8 weeks after DOX; and group V, rats were trained for 3 weeks before DOX followed by 8 weeks after. Measures of oxidative damage (H2O2, catalase), inflammation (TNF-α), and glucose transporter 4 (GLUT4) expression on skeletal muscle were assessed. Also, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was estimated. Skeletal performance was evaluated by contraction time (CT), half relaxation time (1/2 RT), and force-frequency relationship by the end of this research. The current study demonstrated a detrimental effect of DOX on skeletal performance as evidenced by a significant increase in CT and 1/2 RT compared to control; in addition, H2O2, TNF-α, and HOMA-IR were significantly increased with a significant decrease in GLUT4 expression and catalase activity. Combined exercise therapy showed a remarkable improvement in skeletal muscle performance, compared to DOX, CT, and 1/2 RT which were significantly decreased; H2O2 and TNF-α were significantly decreased unlike catalase antioxidant activity that significantly increased; in addition, skeletal muscle glucose metabolism was significantly improved as GLUT4 expression significantly increased and HOMA-IR was significantly decreased. Exercise therapy showed significant improvement in all measured parameters relative to DOX. However, combined exercise therapy showed the best improvement relative to both pre-exercise and post-exercise groups.

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats.

BACKGROUND: Ageing is the primary risk factor for Parkinson's disease. Progressive motor and coordination decline that occurs with ageing has been linked to nigrostriatal dysfunction. Few studies have investigated the efficacy of mesenchymal stem cells in ameliorating the structural and functional alterations in the ageing nigrostriatal system. This study is the first to evaluate the effects of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose- induced rat model of nigrostriatal ageing. MATERIALS AND METHODS: BMMSCs were intravenously injected once every 2 weeks for 8 weeks. The transplanted cells survived, migrated to the brain, and differentiated into dopaminergic neurones and astrocytes. RESULTS: BMMSC transplantation improved locomotor activity, restored dopaminergic system function, preserved atrophic dopaminergic neurones in the substantia nigra, exerted antioxidative effects, and restored neurotrophic factors. CONCLUSIONS: Our findings demonstrate the efficacy of BMMSC injection in a nigrostriatal ageing rat model, and suggest that these cells may provide an effective therapeutic approach for the ageing nigrostriatal system.

The extent of involvement of ouabain, hippocampal expression of Na+/K+-ATPase, and corticosterone/melatonin receptors ratio in modifying stress-induced behavior differs according to the stressor in context.

The aim of this study was to assess the effect of two types of stressors, regarding the extent of involvement of ouabain (OUA), hippocampal sodium/potassium ATPase (NKA) expression, and the hippocampal corticosterone receptors (CR)/melatonin receptors (MR) expression ratio, on the behavioral and cardiovascular responses and on the hippocampal cornu ammonis zone 3 (CA3) and dentate gyrus (DG). Thirty adult male Wistar albino rats aged 7-8 months were exposed to either chronic immobilization or a disturbed dark/light cycle and treated with either ouabain or vehicle. In the immobilized group, in the absence of hippocampal corticosterone (CORT) changes, rats were non-responsive to stress, despite experiencing increased pulse rate, downregulated hippocampal sodium/potassium pump, and enhanced hippocampal CR/MR expression ratio. Prolonged darkness precipitated a reduced upright attack posture, with elevated CORT against hippocampal MR downregulation. Both immobilization and, to a lesser extent, prolonged darkness stress resulted in histopathological and ultrastructural neurodegenerative changes in the hippocampus. OUA administration did not change the behavioral resilience in restrained rats, despite persistence of the underlying biochemical derangements, added to decreased CORT. On the contrary, with exposure to short photoperiods, OUA reverted the behavior towards a combative reduction of inactivity, with unvaried CR/MR and CORT, while ameliorating hippocampal neuro-regeneration, with co-existing NKA and MR repressions. Therefore, the extent of OUA, hippocampal NKA expression, and CR/MR expression, and subsequent behavioral and cardiac responses and hippocampal histopathology, differ according to the type of stressor, whether immobilization or prolonged darkness.

Preventive effects of bone marrow-derived mesenchymal stem cell transplantation in a D-galactose-induced brain aging in rats.

BACKGROUND: Aging is a complex process accompanied by numerous morphological, functional, and metabolic impairments in the brain, and a critical risk factor involved in the increasing incidence of neurodegenerative diseases. Few studies have evaluated the efficacy of different sources of mesenchymal stem cells (MSCs) in ameliorating the early morphological and functional alterations in the aging brain. This study, for the first time, evaluated the potential efficacy of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose-induced rat model of brain aging. MATERIALS AND METHODS: BMMSCs (1 × 106) were intravenously injected into brain aging model rats once every 2 weeks for 8 weeks. RESULTS: The transplanted cells survived and migrated to the brain, and differentiated into astrocytes and neurons, including choline acetyltransferase neurons. BMMSC transplantation improved locomotor activity and cognitive functions, restored cholinergic system function, protected atrophic cholinergic neurons in the basal forebrain, induced antioxidative effects and restored neurotrophic factors, and modulated hippocampal synaptic plasticity by upregulating PSD95 and Egr1 expression. CONCLUSIONS: Our findings demonstrated the efficacy of BMMSC injection in an aging rat model and suggest that these cells may be developed into an effective cell therapy for the aging brain.

The role of the adipose tissue-derived mesenchymal stem cells enriched with melatonin in pancreatic cellular regeneration.

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (AD-MSCs) were proved to differentiate into insulin-producing cells (IPCs), but the amount of insulin secreted was relatively low compared to the insulin secreted by mature pancreatic islets. Enrichment of MSCs culture with melatonin (MT) was found to promote cartilage matrix synthesis, osteogenic and neuronal differentiation. Therefore, the present study was conducted to evaluate the potential role of MT pre-treated AD-MSCs in enhancing the treatment and regeneration of the islet cells of Langerhans in rats with diabetes induced by streptozotocin (STZ). MATERIALS AND METHODS: Forty adult male Sprague Dawley albino rats were divided equally into groups; group I (control group), group II (STZ group), group III (STZ + AD-MSCs) and group IV (STZ+MT pre-treated AD-MSCs). Biochemical studies were implemented including measurements of the body weight, fasting blood glucose and serum insulin levels, Interleukin 17 (IL-17) and IL-10. Samples of the pancreas were taken and prepared for light, fluorescent microscopic examination, proliferating cell nuclear antigen and caspase-3 immunohistochemical studies and histomorphometric analysis. RESULTS: The present study confirmed the regenerative and therapeutic effects of AD-MSCs on the pancreatic cells. Concomitant supply of MT to the culture of AD-MSCs, in group IV, was shown to retain the normal architecture of the islet cells of Langerhans. They appeared well-defined and lightly stained, surrounded by classical pancreatic acini and contained a large number of islet cells with vesicular nuclei and prominent nucleoli. Improvement of all the biochemical parameters, in the same group, was demonstrated by increased body weight and serum insulin levels with a decrease in the fasting blood glucose levels. Significant decrease in the pro-inflammatory cytokine; IL-17 and increase in the anti-inflammatory cytokine; IL-10, compared to the STZ group, were also discovered. Significant increase in the proliferating cell nuclear antigen proliferation index, decrease in caspase-3 and increase in PKH26 labelled MSCs area per cent was recorded in the group of AD-MSCs enriched with MT compared to the group of AD-MSCs without MT. CONCLUSIONS: The present study confirmed the potential therapeutic and protective role of MT pre-treated AD-MSCs against the STZ-induced pancreatic islet cells damage. Further studies are recommended to investigate the efficacy of MT and AD-MSCs over longer experimental durations.

Hospital Ownership, Geographic Region, Patient Age, Comorbidities, and Insurance Status Appear to Influence Patient Selection Robot-Assisted Ureteral Reimplantation for Benign Disease: A Population-Based Analysis.

Background: Robot-assisted ureteral reimplantation (RAUR) is a relatively new minimally invasive procedure. As such, research is lacking, and the largest adult cohort studies include fewer than 30 patients. Our aim was to be the first population-based study to report on national utilization trends, factors associated with patient selection, inpatient outcomes, and the relative cost of RAUR for adults with benign ureteral disease (BUD). Materials and Methods: The National Inpatient Sample (2010-2015) was queried to identify all elective, nontransplant-related, open and robot-assisted reimplants for adult BUD. Survey-weighted logistic regression using Akaike Information Criterion identified patient-/hospital-level factors associated with robotic procedure. Survey-weighted regression models examined the association of robotic procedure with outcomes and charges. Results: A weighted total of 9088 cases were included: 1688 (18.6%) robot assisted and 7400 (81.4%) open. There were significantly increased odds of RAUR across consecutive years (odds ratio [OR] = 3.0, p < 0.001) and among patients operated on at private for-profit hospitals (OR: 2.1; p = 0.01), but significantly decreased odds among older patients (OR = 0.98, p < 0.001), those with Medicaid (OR = 0.5, p = 0.02), those with 2+ comorbidities (OR = 0.6, p = 0.009), and those operated on in western (OR = 0.5; p = 0.005) states. RAUR was significantly associated with a reduced length-of-stay (incidence rate ratio: 0.60; p < 0.001), decreased odds of blood transfusion (OR = 0.40; p < 0.001), and a lower mean ratio of total hospital charges (ratio: 0.71; p = 0.006). Conclusions: This is the first population-based study to report on the utilization and clinical benefits of RAUR for adult BUD. Open reimplantation remains the most common surgical technique utilized, despite the potential benefits of RAUR. Future research is needed to explore the mechanisms behind patient-/hospital-level factors and surgical selection. Work to investigate potential barriers in access to robotic procedure can help us provide equitable care across patient populations.

The extent of involvement of ouabain, hippocampal expression of Na+/K+-ATPase, and corticosterone/melatonin receptors ratio in modifying stress-induced behavior differs according to the stressor in context

The aim of this study was to assess the effect of two types of stressors, regarding the extent of involvement of ouabain (OUA), hippocampal sodium/potassium ATPase (NKA) expression, and the hippocampal corticosterone receptors (CR)/melatonin receptors (MR) expression ratio, on the behavioral and cardiovascular responses and on the hippocampal cornu ammonis zone 3 (CA3) and dentate gyrus (DG). Thirty adult male Wistar albino rats aged 7-8 months were exposed to either chronic immobilization or a disturbed dark/light cycle and treated with either ouabain or vehicle. In the immobilized group, in the absence of hippocampal corticosterone (CORT) changes, rats were non-responsive to stress, despite experiencing increased pulse rate, downregulated hippocampal sodium/potassium pump, and enhanced hippocampal CR/MR expression ratio. Prolonged darkness precipitated a reduced upright attack posture, with elevated CORT against hippocampal MR downregulation. Both immobilization and, to a lesser extent, prolonged darkness stress resulted in histopathological and ultrastructural neurodegenerative changes in the hippocampus. OUA administration did not change the behavioral resilience in restrained rats, despite persistence of the underlying biochemical derangements, added to decreased CORT. On the contrary, with exposure to short photoperiods, OUA reverted the behavior towards a combative reduction of inactivity, with unvaried CR/MR and CORT, while ameliorating hippocampal neuro-regeneration, with co-existing NKA and MR repressions. Therefore, the extent of OUA, hippocampal NKA expression, and CR/MR expression, and subsequent behavioral and cardiac responses and hippocampal histopathology, differ according to the type of stressor, whether immobilization or prolonged darkness.

Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)

Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34+ stem cells (6×106 cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

Elevated serum tumour necrosis factor-like weak inducer of apoptosis in alopecia areata: a possible marker of disease severity.

BACKGROUND: Alopecia areata (AA) is, an organ-specific autoimmune disease, characterized by an aberrant expression of cytokines of the T helper 1 type. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifactorial cytokine that exerts a role in the pathogenesis of inflammatory and autoimmune diseases, especially in cutaneous diseases. AIM: To estimate the serum level of TWEAK in AA and to correlate it with different parameters. METHODS: This case-control study enrolled 40 patients with AA and 50 clinically healthy volunteers matched for age and sex. A blood sample (5 mL) was extracted from each participant for analysis of serum TWEAK levels by ELISA. RESULTS: Levels of TWEAK were significantly higher in patients with AA (mean ± SD 213.7 ± 59.2 pg/mL, range 109.1-341.6 pg/mL) than in controls (95.97 ± 13.28 pg/mL, range 80.1-152.3 pg/mL) (P < 0.001). A significant positive correlation was found between serum TWEAK level and the Severity of Alopecia Tool (SALT) score (r = 0.56, P < 0.001). CONCLUSION: To our knowledge, this study highlights for the first time a possible link between higher serum TWEAK level and AA. Serum TWEAK level appears to reflect AA disease severity.

Therapeutic role of bone marrow mesenchymal stem cells in diabetic neuronal alternations of rat hippocampus.

BACKGROUND: As the hippocampus is the main brain region for many forms of learning and memory functions and is acutely sensitive to blood glucose changes, diabetes mellitus, which is a serious metabolic disease, is often accompanied by learning and memory deficits. Through scientific literatures, mesenchymal stem cells (MSCs) promote functional recovery in rats with traumatic brain injury, so the present work was conducted to study MSCs as a possible treatment for the diabetic neuronal degeneration and functional impairment of rat hippocampus. MATERIALS AND METHODS: It was carried out using male albino rats: non-diabetic control groups (4, 8, 12 weeks) (n = 15), diabetic groups by i.v. injection of streptozotocin for (4, 8, 12 weeks) (n = 15) and MSCs treatment to diabetic groups for (8, 12 weeks) (n = 10). Hippocampal learning and memory functions were assessed by the Morris Water Maze test and its results were statistically analysed. The rat hippocampal regions (CA1 and CA3) were subjected to histological, ultrastructural examination and morphometrical analyse of pyramidal neurons. RESULTS: Neurons of the diabetic groups showed disturbed function and architecture; shrunken hyperchromatic nuclei and vacuolated eosinophilic cytoplasm (apoptotic changes) also MSCs treatment improved hippocampal learning and memory functions plus its architectural changes; increasing populations and normal regular distribution. CONCLUSIONS: It can be concluded that diabetic hippocampal neuronal alternations and functional impairment can be ameliorated by MSCs treatment.

Role of the cutaneous extraneuronal cholinergic system in the pathogenesis of psoriasis: a case-control study.

BACKGROUND: Although during recent years there have been considerable advances in elucidating the mechanisms of psoriasis pathogenesis, its full understanding is still distant. A cholinergic dysfunction has been proposed in the pathophysiology of some inflammatory and autoimmune diseases, including psoriasis. AIM: To determine tissue levels of acetylcholine (ACh) and its muscarinic and nicotinic receptors (mAChR and nAChR) in psoriasis vulgaris lesions in comparison with normal control skin. METHODS: This case-control study included 30 patients with psoriasis vulgaris and 30 controls. A 4-mm punch skin biopsy was taken from the psoriatic plaques of patients and normal skin of controls. ACh level was measured in tissues using the colorimetric method, while mAChR and nAChR gene expression was determined by real-time PCR. RESULTS: The level of ACh was significantly higher in patients (mean ± SD: 5.95 ± 2.69) than in controls (1.12 ± 0.34) (P < 0.001). mAChR and nAChR expressions were significantly higher in patients compared with the controls (P < 0.001). A significant positive correlation was detected between the expression of nAChR in patients and the duration of psoriasis (r = 0.46, P = 0.01), and the body mass index of the patients correlated positively with both nAChR (r = 0.40, P = 0.027) and mAChR expression (r = 0.448, P = 0.013). CONCLUSION: Abnormalities in the cutaneous extraneuronal cholinergic system could be involved in the pathogenesis of psoriasis. The high expression of nAChRs in patients with longer disease durations might represent an attempt by the body to regulate the inflammatory cascade in psoriatic lesions. The high expression of mAChR in psoriatic lesions may provide a link between psoriasis and obesity.

Assessment of telomerase activity in nonsegmental vitiligo tissue: a pilot study.

BACKGROUND: Vitiligo is characterized by loss of melanocytes; therefore, an increased risk of photoageing and cancer are expected. However, a low incidence of cancer and sun damage in vitiliginous skin has been reported. Telomerase is a specialized cellular enzyme catalysing the synthesis of telomeres, and an increased level of the telomerase activity has been highlighted in most of human cancer cells and cancer cell lines. AIM: To assess relative telomerase activity (RTA) among patients with nonsegmental vitiligo. METHODS: In this case-control study, skin biopsy specimens were taken from 20 patients (one from lesional and another from nonlesional skin) and from sun-protected skin from 10 healthy age-, sex- and skin phototype-matched healthy controls. PCR ELISA was performed for assessment of RTA. RESULTS: RTA in lesional skin biopsies from patients with nonsegmental vitiligo was significantly decreased compared with nonlesional skin and healthy control skin samples, with no significant difference between the latter two. RTA in lesional skin was negatively correlated with Vitiligo Area Scoring Index but not correlated with Vitiligo Disease Activity score or RTA of nonlesional skin. Neither lesional nor nonlesional RTA levels showed any correlation with patient sex, age, skin phototype or with disease duration. CONCLUSION: Low levels of RTA in vitiliginous skin may help to explain the lower chance of developing skin cancer and decreased incidence of actinic damage in vitiliginous skin.

α-Lipoic acid and amlodipine/perindopril combination potentiate the therapeutic effect of mesenchymal stem cells on isoproterenol induced cardiac injury in rats.

Cardiac injury is a dangerous disease and become a greater issue in the forthcoming decades. The ultimate goal is to prevent the progression of heart failure and apoptotic processes. Cardiac tissue may regenerate itself but to certain extent depending on the number of resident stem cells that is limited. Thus, research had been focused on bone marrow derived stem cells (BM-MSCs) as a promising therapy in different types of tissues, including the heart. This study is designed not only to assess the therapeutic effect of BM-MSCs but also to improve their therapeutic effect in combination with antioxidant α-lipoic acid (ALA) and antihypertensive therapeutic drug form (AP) against isoproterenol-induced cardiac injury and compared with that of BM-MSCs alone. Cardiac injury was induced in 70 male rats by Isoproterenol (ISO was injected s.c. for four consecutive days). Experimental animals were divided into six ISO-treated groups beside a control non treated one. The six ISO-treated groups were divided into: ISO group, ISO+BM-MSCs group, ISO+ALA group, ISO+AP group, ISO+ALA+AP group and ISO+ALA+AP+BM-MSCs group, the last five groups were treated with the examined materials after one week of ISO injection. Isoproterenol significantly increased serum CK-MB, LDH activities, Troponin1 and TNF-α. Oxidative stress is evidenced by the increased MDA, NO and Caspase-3 activity associated with significant reduction of GSH content and SOD activity in cardiac tissue. Furthermore, mRNA expression of NFκB and iNOS were significantly up regulated and eNOS mRNA expression was down regulated. Administration of BM-MSCs, ALA and AP alone significantly mitigated the induced cardiac injury. Concomitant administration of ALA and AP after BM-MSCs induced a more pronounced improving effect on cardiac functions. In conclusion, the concomitant administration of ALA and AP after BM-MSCs infusion increases the cellular antioxidant levels of cardiac tissue that improves the repairing function of BM-MSCs.

Effect of glucagon-like peptide-1 analogue; Exendin-4, on cognitive functions in type 2 diabetes mellitus; possible modulation of brain derived neurotrophic factor and brain Visfatin.

BACKGROUND: Brain derived neurotrophic factor (BDNF) is one of the most essential neurotrophic factors in the brain. BDNF is involved in learning, memory and locomotion suggesting it as a target in type 2 diabetes mellitus (T2DM) associated cognitive changes. Visfatin; an adipokine discovered to be expressed in the brain; was found to have multiple effects including its participation in keeping energy supply to the cell and is consequentially involved in cell survival. Its role in cognitive functions in T2DM was not studied before. Recent studies point to the possible neuro-protective mechanisms of glucagon-like peptide 1 analogue: Exendin-4 (Ex-4) in many cognitive disorders, but whether BDNF or Visfatin are involved or not in its neuro-protective mechanisms; is still unknown. AIMS: to study the changes in cognitive functions in T2DM, either not treated or treated with Glucagon-like peptide 1 (GLP-1) analogue: Ex-4, and to identify the possible underlying mechanisms of these changes and whether BDNF and brain Visfatin are involved. METHODS: A total of 36 adult male wistar albino rats were divided into 4 groups; Control, Exendin-4 control, Diabetic and Exendin-4 treated groups. At the end of the study, Y-maze and open field tests were done the day before scarification to assess spatial working memory and locomotion, respectively. Fasting glucose and insulin, lipid profile and tumor necrosis factor- alpha (TNF-α) were measured in the serum. Homeostasis model assessment insulin resistance was calculated. In the brain tissue, malondialdehyde (MDA) level, gene expression and protein levels of BDNF and Visfatin, area of degenerated neurons, area of glial cells and area % of synaptophysin immunoexpression were assessed. RESULTS: Compared with the control, the untreated diabetic rats showed insulin resistance, dyslipidemia and elevation of serum TNF-α. The brain tissue showed down-regulation of BDNF gene expression and reduction of its protein level, up-regulation of Visfatin gene expression and elevation of its protein level, increase in MDA, area of degenerated neurons and area of glial cells and reduction in area % of synaptophysin immunoexpression. These changes were paralleled with significant deterioration in spatial working memory and locomotion. Treatment of diabetic rats with Ex-4 reversed all these changes. CONCLUSION: T2DM has a negative impact on cognitive functions through different pathological and subcellular mechanisms. The current study provides evidence for involvement of BDNF and brain Visfatin in T2DM- associated cognitive dysfunction. BDNF and brain Visfatin were also found to contribute to the neuro-protective effect of Ex-4 via modulation of inflammation, oxidative stress, neuro-degeneration and synaptic function.

Seminal SIRT1 expression in infertile oligoasthenoteratozoospermic men with varicocoele.

In a case-controlled study, we assessed the expressed seminal NAD-dependent protein deacetylase (SIRT1) expression in infertile oligoasthenoteratozoospermic (OAT) men associated with varicocoele. Our study involved 81 men, recruited from the University hospitals, after ethical approval and informed consent. They were allocated into fertile normozoospermic men (n = 23), infertile OAT men without varicocoele (n = 23) and infertile OAT men with varicocoele (n = 35). Inclusion criteria consisted of confirmation of abnormal semen parameters and normal female partners whereas exclusion criteria were leukocytospermia, tobacco smoking, hormonal therapy, immunological disorders, dyslipidemia, hypogonadism, cardiovascular disorders, morbid obesity, and hepatic or renal failures. All participants had an interview to assess clinical history, clinical examination, semen analysis, and estimation of seminal SIRT1 expression. Seminal SIRT1 expression was significantly lower in infertile OAT men than fertile men. Among infertile OAT men, seminal SIRT1 expression was significantly lower in those with varicocoele than in those without. Additionally, seminal SIRT1 expression was significantly lower in varicocoele grade III cases compared with other grades. Seminal SIRT1 expression was positively correlated with sperm concentration (r = 0.327, p = 0.001), total sperm motility (r = 0.532, p = 0.001), and sperm normal forms (r = 0.469, p = 0.001). Our results suggest that seminal SIRT1 expression has a role of male infertility being significantly decreased in infertile OAT men in general and in infertile OAT men associated with varicocoele in particular.

Effects of occupational exposure to aluminium on some oxidative stress and DNA damage parameters.

AIM: The aim of this work was to investigate the relationships between aluminium levels, oxidative status and DNA damage in workers occupationally exposed to aluminium. SUBJECTS AND METHODS: This study was conducted in a secondary aluminium smelter. It included 96 male workers occupationally exposed to aluminium fume and dust compared to 96 male nonexposed individuals. Full history and clinical examination were done for all participants. Laboratory investigations in the form of serum aluminium, total antioxidant capacity (TAC), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and comet assay test were performed. RESULTS: Serum aluminium level ranged from 4 to 30 µg/L of median: 10 µg/L; urinary 8-OHdG ranged from 2.7 to 17.2 ng/mg creatinine of median: 7.6 ng/mg creatinine; comet tail length (CTL) ranged from 19.7 to 50.5 µm of median: 45 µm, were statistically significantly increased in the exposed group compared to nonexposed group. In exposed workers, a statistically significant positive correlations were found between serum aluminium level and urinary 8-OHdG ( r = 0.75, p < 0.001); aluminium level and CTL ( r = 0.71, p < 0.001); and urinary 8-OHdG and CTL ( r = 0.71, p < 0.001). There was a statistically significant negative correlation between serum aluminium and TAC ( r = -0.76, p < 0.001). CONCLUSION: Occupational exposure to aluminium in secondary aluminium smelters was related to the induction of oxidative stress and DNA damage. This may promote the development of adverse health hazards in the exposed workers.

In vitro evaluation of the human gingival fibroblast/gingival mesenchymal stem cell dynamics through perforated guided tissue membranes: cell migration, proliferation and membrane stiffness assay.

BACKGROUND: Migration of gingival fibroblasts/gingival mesenchymal stem cells through macro-perforated barrier membranes may allow them to participate positively in periodontal regeneration. The optimal guided tissue membrane perforation diameter that could favor maximum cell migration into the defect area and at the same time act as an occlusive barrier for gingival epithelium and its associated gingival extracellular matrix component is not yet identified. MATERIAL AND METHODS: Cultured human gingival fibroblasts/gingival mesenchymal stem cells were placed in the upper chambers of 12-well collagen-coated polytetrafluoroethylene transwells, which were manually perforated with 0.2, 0.4 and 0.7 mm sized pores. The lower chambers of the transwells received blood clot as an attraction medium. The number of cells that have migrated to the lower chambers was calculated. Proliferation of these cells was evaluated using MTT assay. Scanning electron microscopy images were obtained for the lower surfaces of the transwell membranes. Perforated bovine collagen membranes (Tutopatch® ) were subjected to mechanical testing to determine the tensile strength and modulus of elasticity. RESULTS: Group 3 (0.7 mm) showed significantly higher values for cell migration and proliferation. All groups showed a small degree of extracellular matrix migration through membrane perforations. Scanning electron microscopy evaluation revealed variable numbers of cells in fibrin matrices located mainly around the pore edges. There were non-significant differences between groups regarding mechanical properties. CONCLUSIONS: The present study demonstrated that macro-membrane perforations of 0.2, 0.4 and 0.7 mm are suitable pore diameters that could maintain membrane stiffness and allow for cellular migration. However, these membrane perforation diameters did not allow for total gingival connective tissue isolation.

Toll-like receptor (TLR)7 expression in mycosis fungoides and psoriasis: a case-control study.

BACKGROUND: Toll-like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T-cell lymphoma (CTCL). AIM: To detect TLR7 gene expression in mycosis fungoides (MF) (a neoplastic skin condition) and to compare it with psoriasis (an inflammatory skin condition) in an attempt to clarify the pathogenic role played by TLR7 in both conditions. METHODS: This case-control study enrolled 28 patients with MF: 30 patients with psoriasis, and 30 age- and sex-matched healthy controls (HCs). A 4-mm punch skin biopsy was obtained from lesional skin of patients and from normal skin of HCs for detection of TLR7 gene expression using real-time PCR. RESULTS: Mean TLR7 level in patients with MF (0.4 ± 0.23) was significantly lower than in patients with psoriasis (1.49 ± 0.46) and in HCs (1.22 ± 0.44) (P < 0.001), and mean TLR7 level in patients with psoriasis was significantly higher than in HCs (P < 0.03). Based on MF staging, 21.4% of patients had stage Ia, 28.6% had stage Ib, 28.6% had stage IIa and 21.4% had stage IIb disease. Comparing the TLR7 levels in relation to MF staging revealed the lowest mean value was in stage IIb and highest mean value in stage Ia, and this was significant (P < 0.001). CONCLUSION: Disturbed innate immunity might play a role in the pathogenesis of neoplastic and inflammatory skin conditions. TLR7 could be useful as a prognostic factor in MF.

Possible role of proenkephalin in psoriasis.

BACKGROUND: Psoriasis is a common chronic skin disease that can also affect the mucous membranes and joints. It is multifactorial in origin, occurring in genetically predisposed individuals, and triggered by various endogenous and exogenous factors. Proenkephalin (PENK) is an endogenous opioid polypeptide hormone that acts on specific opiate receptors found on nerve and mucosal cells, and on various cells in the immune system. PENK receptors are expressed on skin cells, and their activation can regulate keratinocyte and melanocyte activities. PENK expression has been found to be increased in keratinocytes in psoriatic skin, and together with its inflammatory basis, this suggests that PENK may be regulated by inflammatory stimuli. AIM: To assess the possible role of PENK in the pathogenesis of psoriasis and to assess if it is related to the severity of psoriatic lesions. METHODS: Serum and tissue PENK levels were estimated in 20 patients with psoriasis vulgaris, and compared with those of 20 healthy controls (HCs). RESULTS: PENK levels were found to be significantly increased both in serum and in psoriatic lesions in patients compared with HCs. No significant correlation was found between PENK levels and patient age, disease duration or disease severity (Psoriasis Area and Severity Index). CONCLUSION: Our results support the role of PENK in the aetiopathogenesis of psoriasis, and indicate that giving anti-PENK drugs in addition to current antipsoriatic therapies might be of value in treating this common chronic skin disease.

Reduction in tissue plasmin: a new mechanism of action of narrowband ultraviolet B in psoriasis.

BACKGROUND: Plasmin (PL) is a potent inflammatory cell activator, and ultraviolet (UV)B has immunomodulatory effects on cutaneous inflammatory responses. There are no previous studies comparing the effect of narrowband (NB)-UVB on tissue PL levels in psoriasis. AIM: To estimate the possible role of PL in the pathogenesis of psoriasis, and to evaluate the effect of NB-UVB on tissue PL in psoriasis. METHODS: This case-control study enrolled 21 patients with psoriasis and 20 clinically healthy volunteers matched for age and sex. Patients underwent 24 sessions of NB-UVB radiation. Biopsy samples using a 4 mm punch were taken from all patients before and after treatment and from the controls for estimation of tissue PL level by ELISA. RESULTS: Tissue PL was significantly upregulated in psoriasis before treatment (mean ± SD 1.73 ± 1.23 ng/mg protein) compared with controls (0.21 ± 0.15 ng/mg protein) (P < 0.001). A statistically significant positive correlation (P = 0.02) was found between the tissue PL before treatment and the Psoriasis Area and Severity Index. Patients received 24 sessions of NB-UVB, with a mean cumulative dose of 23.25 ± 8.14 mJ/cm(2) . Tissue PL levels were reduced by a mean of 30.3% post-treatment compared with baseline (P < 0.001). The reduction in Pl levels was significantly correlated with the cumulative dose of NB-UVB, and with the percentage reduction in PASI (P < 0.001). CONCLUSIONS: Our study highlights the possible role played by tissue PL level in the pathogenesis of psoriasis. PL level appears to reflect disease severity, and is a possible marker of therapeutic efficacy of NB-UVB on psoriatic skin.