Objective: To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis. Methods: Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected. Results:Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression ofα-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased. Conclusions:The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s).

OBJECTIVETo evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis.

METHODSFemale albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected.

RESULTSKidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased.

CONCLUSIONSThe obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s).

Animals ; Female ; Isoantibodies ; toxicity ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; metabolism ; Nephritis ; chemically induced ; surgery ; Rats

BACKGROUND: Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms. METHODS: Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed. RESULTS: Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats. CONCLUSIONS: This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.
Adult ; Animals ; Autistic Disorder ; Child ; Dexmedetomidine ; Electroencephalography ; Female ; gamma-Aminobutyric Acid ; Gene Expression ; Glutamic Acid ; Humans ; Infant, Newborn ; Male ; Models, Animal ; N-Methylaspartate ; Neurodevelopmental Disorders ; Propofol ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; Receptors, Glutamate ; Reflex, Righting ; Valproic Acid

BACKGROUND: Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms. METHODS: Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed. RESULTS: Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats. CONCLUSIONS This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.

This article has been retracted at the authors' request.

BACKGROUND AND OBJECTIVES: Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. METHODS AND RESULTS: Oral ulcers were induced by topical application of formocresol in the oral cavity of dogs. Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was injected around the ulcer in each group. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was detected in biopsies from all ulcers. Results: MSCs expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs-treated ulcers compared to controls. CONCLUSIONS: MSCs transplantation may help to accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression. This body of work has provided evidence supporting clinical applications of adipose-derived cells in safety and efficacy trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer healing.
Adipose Tissue ; Adult Stem Cells ; Animals ; Biopsy ; Bone Marrow ; Collagen ; Dogs ; Formocresols ; Gene Expression ; Mesenchymal Stromal Cells ; Mouth ; Oral Ulcer ; Regenerative Medicine ; RNA, Messenger ; Stem Cells ; Tissue Engineering ; Transplants ; Ulcer ; Vascular Endothelial Growth Factor A

BACKGROUND AND OBJECTIVES: Irradiated wound healing is a highly complex and dynamic process. The latest technology making a huge difference in this process is stem cell therapy. The goal of this study was to evaluate the use of bone marrow-derived mesenchymal stem cells (BM-MSCs) or human amniotic epithelial cells (HAECs) in the healing of irradiated wounds. METHODS AND RESULTS: Forty five male albino rats were subjected to whole body 6 gray gamma radiations. One day post irradiation, full-thickness incisional wound was created in the tibial skin. The rats were randomly equally divided into three groups. The incisions of the first group (gp I) were injected intra-dermally with saline before stitching and those of both the second (gp II) and the third groups (gp III) were intradermally injected with BM-MSCs and HAECs before stitching respectively. Animals were sacrificed after the third, seventh and fourteenth days postoperative. The healing process was assessed histopathologically. CXCL-5, SDF-1 and Transforming growth factor-beta 1 (TGF-beta1) expression were also detected in biopsies from all wounds. Expression of TGF-beta1 in gp I was more than the other groups leading to severe inflammation, deficient healed dermis and delayed reepithelialization. SDF-1 expression was high in gp II while CXCL-5 expression was high in gp III causing accelerated wound healing. BM-MSCs showed a great effect on the quality of the dermis, while superiority of the epithelium and its appendages were achieved in HAECs group. CONCLUSIONS: Using BM-MSCs and HAECs could be used safely in case of irradiated wounds.
Animals ; Biopsy ; Dermis ; Epithelial Cells ; Epithelium ; Gamma Rays ; Humans ; Inflammation ; Male ; Mesenchymal Stromal Cells ; Rats ; Skin ; Stem Cells ; Transforming Growth Factor beta1 ; Wound Healing

BACKGROUND: Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. Toll-like receptors (TLRs) play an important role in immune responses and in the pathophysiology of inflammatory skin diseases. Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. METHODS: Twenty-four PR patients and 24 healthy individuals (as controls) were included in this case control study. All recruits were subjected to routine laboratory investigations. Biopsies were obtained from one active PR lesion and from healthy skin of controls for the detection of TLR 3, 7, 8, and 9 gene expression using real-time polymerase chain reaction. RESULTS: This study included 24 patients (8 females and 16 males) with active PR lesions, with a mean age of 28.62 years. Twenty four healthy age- and sex-matched individuals were included as controls (8 females and 16 males, with a mean age of 30.83 years). The results of the routine laboratory tests revealed no significant differences between both groups. Significantly elevated expression of all studied TLRs were detected in PR patients relative to healthy controls (p < .001). CONCLUSIONS: TLRs 3, 7, 8, and 9 might be involved in the pathogenesis of PR.

AIMTo assess heme oxygenase-1 (HO-1) activity in the cavernous tissue of sildenafil citrate-treated rats.

METHODSOne hundred and ninety-two Sprague-Dawley male rats, divided into four equal groups, were investigated. Group 1, the control group, received regular animal chow; group 2 received sildenafil citrate by intragastric tube; group 3 received sildenafil and HO inhibitor (zinc protoporphyrin, ZnPP); and group 4 received sildenafil and nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME). Twelve rats from each group were killed after 0.5 h, 1 h, 2 h and 3 h of drug administration. Then HO-1 activity, cGMP levels and NOS enzymatic activity in the cavernous tissues were estimated.

RESULTSIn cavernous tissue, HO-1 activity, NOS enzymatic activity and cGMP concentration increased significantly in sildenafil-treated rats compared to other groups throughout the experiment. Rats receiving either HO or NOS inhibitors showed a significant decrease in these parameters. HO-1 cavernous tissue activity and NOS enzymatic activity demonstrated a positive significant correlation with cGMP levels (r = 0.646, r = 0.612 respectively; P < 0.001).

CONCLUSIONThe actions of PDE5 inhibitor sildenafil citrate in the cavernous tissue are partly mediated through the interdependent relationship between both HO-1 and NOS activities.

Administration, Oral ; Animals ; Cyclic GMP ; metabolism ; Drug Interactions ; Drug Therapy, Combination ; Enzyme Inhibitors ; pharmacology ; Heme Oxygenase-1 ; antagonists & inhibitors ; metabolism ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide Synthase ; metabolism ; Penis ; drug effects ; enzymology ; Piperazines ; pharmacology ; Protoporphyrins ; pharmacology ; Purines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfones ; pharmacology ; Vasodilator Agents ; pharmacology

Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine (500 mg/kg), pyrrolidine dithiocarbamate (100 mg/kg), and saxagliptin (10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase (MAPK), phosphorylated extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), interleukin-12 (IL-12), caspase-3, β-defensin, inducible nitric oxide synthase (iNOS) and glucagon like peptide-1 (GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, iNOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and iNOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.