Effect of Gallic acid on dementia type of Alzheimer disease in rats: electrophysiological and histological studies

Introduction: To study the effect of gallic acid [GA] on hippocampal long-term potentiation [LTP] and histological changes in animal model of Alzheimer disease [AD] induced by beta-amyloid [Abeta]

Methods: Sixty-four adult male Wistar rats [300 +/- 20 g] were divided into 8 groups: 1] Control [Cont]; 2] AD; 3] Sham; 4-7] AD+GA [50, 100, and 200 mg/kg for 10 days, orally] or vehicle, 8] Cont+GA100, Abeta [1microg/microL in each site] was infused into hippocampus bilaterally. Changes of amplitude and slope of LTP induced in hippocampal dentate gyrus [DG] were evaluated by high frequency stimulation [HFS] of perforant path [PP]

Results: Data showed that LTP amplitude and area under curve significantly impaired in AD rats [P<0.001], while significantly improved in AD rats treated with GA [P<0.05, P<0.01]

Conclusion: Current findings suggest that GA reduces neural damage and brain amyloid neuropathology and improves cognitive function via free radicals scavenging and inhibiting oligomerization of Abeta but with no effect on healthy rats

[Effects of Bonium persicum B.Fedtsch fruit ethanolic extract on morphine tolerance and dependence in adult male NMRI mice]

Background: Morphine causes the development of dependence, which limits its usage for chronic pain. Morphine dependence is a compulsive pattern of drug seeking and drug taking, resulting from the positive reinforcement of the rewarding effects of drug taking and the negative reinforcement of withdrawal syndrome that accompanies the cessation of drug taking. The objective of this research was to investigate the effects of caraway [Bonium persicum B.Fedtsch] ethanolic extract on acquisition and expression of morphine tolerance and dependence in mice

Materials and methods: In this experimental study, hot-plate test was used to survey morphine analgesic tolerance. Morphine was injected [2.5, 5, 10, 20, 40 mg/kg, i.p.] twice daily for 7 days, except in 8th day in which morphine was administrated at a single dose [50 mg/kg, i.p.]. The extract [300, 400, 500 mg/kg, i.p.] was injected daily for 8 days. Also, Naloxone was injected [10 mg/kg, i.p.] 5 hours after the final dose of morphine and the withdrawal signs including jumping, abdominal contraction, teeth chattering, grooming, diarrhea, and ptosis were recorded during a period of 30 minutes

Results: Caraway extract significantly attenuated both development and expression of morphine dependence. It significantly reduced jumping, abdominal contraction, teeth chattering, grooming, diarrhea, and ptosis

Conclusion: These findings indicate effectiveness of caraway extract for management of morphine tolerance. Results of this study indicate that the plant contained component[s] that alleviate morphine withdrawal syndrome

Biological behavior study of gelatin coated PCL nanofiberous electrospun scaffolds using fibroblasts

Scaffold design has pivotal role in tissue engineering. In the present study, We modified the surface of electrospun poly[caprolactone] [PCL] nanofibers to improve their compatibility with living medium and to show the potential application of PCL nanofibers as a artificial extracellular matrix using in tissue-engineering. PCL nanofibers were fabricated by electrospinning method. To graft gelatin on the nanofiber surface, PCL scaffolds were first treated with air plasma to introduce carboxyl groups on the surface, followed by covalent grafting of gelatin molecules. The hydrophilicity of the electrospun PCL nanofibers was significantly increased by the gas plasma treatment, as confirmed by contact angle measurements. ATR-FTIR analysis demonstrated that the chemical composition of the PCL nanofiber surface was influenced by the gelatin coating, resulting in an increase in the number of amine groups. Our results show that the modified PCL nanofibers are suitable physical properties as polymeric artificial scaffold in tissue engineering application

[Antidiabetic effect of Artemisia deserti ethanolic extract in normal and streptozotocin-induced diabetic rats]

Many herbal medicines have been recommended for the treatment of diabetes. The genus Artemisia has always been of great botanical and pharmaceutical interest, and is used in traditional medicine for the treatment of various diseases. The present study was performed aiming at investigating the effect of alcoholic extract of the aerial parts of Artemisia deserti in normal and streptozotocin-induced diabetic rats. To induce diabetes, the rats received a single intraperitoneal injection of streptozotocin [70mg/kg]. Ethanolic extract of Artemisia desertiin amounts of [50, 100, 200, and 400mg/kg body weight] were administrated orally for 28 days in normal and diabetic rats. At the end of treatment, the animals were anesthetized and blood samples were collected from their heart. Then, serum levels of glucose, insulin, total cholesterol, triglyceride, urea, uric acid, and creatinine were measured. Data were analyzed by one-way ANOVA and Tukey's test. The significance level was defined as p<0.05. Oral administration of ethanolic extract of aerial parts of Artemisia desertifor 28 days significantly decreased serum levels of glucose, triglyceride, total cholesterol, urea, uric acid, and creatinine in the diabetic rats. Also, oral administration of the plant extract significantly increased serum insulin level in diabetic rats. Oral administration of the extract caused no significant change in the levels of the above mentioned parameters in normal rats. The results of the present study showed that Artemisia deserti has antidiabetic effect in rats and can be considered for therapeutic purposes

Induction of IFN-gamma cytokine response against hepatitis B surface antigen using melittin

In this study we co-administered melittin along with HBsAg/alum vaccine to investigate if it helps elicitation of Th1/Th2 response. Hepatitis B virus [HBV] infection is a life-threatening liver infection, which can lead to chronic liver disease. Vigorous T cell responses are stimulated at acute, self-limiting HBV infection, while chronic HBV infection elicits very weak T cell responses. The prevalence of HBV infection has been decreased by the approved vaccination approach using recombinant HBs antigen [HBsAg] and alum i.e. HBV vaccine. Alum, a strong Th2 stimulator, is usually used as adjuvant to increase HBsAg immunogenicity. The present vaccine does not induce protective and/or prophylactic immune response in some groups. Melittin, major active component in the venom of honeybee, induces Th1 development. Experimental mice were immunized with melittin plus hepatitis B vaccine on day 0 following by two booster doses with the same injections. Lymphocyte proliferation, IFN-gamma, and IL-4 level, total antibody and isotyping of IgG1, IgG2a IgG2b, and IgM were measured using ELISA. Administration of melittin and HBV vaccine had no effect on lymphoproliferation and total antibody responses, but increased IFN-gamma response and induced Th1 response. The present study proposed that administration of melittin along with conventional vaccine shifts T cell responses towards Th1/Th2 dominated with Th1 response. The resultant immune response leads to activation of both cell-mediated and humoral immune responses, both of which required for clearance of HBV infection.

Neuronal differentiation of rat hair follicle stem cells: the involvement of the neuroprotective factor seladin-1 [DHCR24]

The seladin-1 [selective Alzheimer disease indicator-1], also known as DHCR24, is a gene found to be down-regulated in brain region affected by Alzheimer disease [AD]. Whereas, hair follicle stem cells [HFSC], which are affected in with neurogenic potential, it might to hypothesize that this multipotent cell compartment is the predominant source of seladin-1. Our aim was to evaluate seladin-1 gene expression in hair follicle stem cells. In this study, bulge area of male Wistar rat HFSC were cultured and then characterized with Seladin-1 immunocytochemistry and flow cytometry on days 8 to 14. Next, 9-11-day cells were evaluated for seladin-1 gene expression by real-time PCR. Our results indicated that expression of the seladin-1 gene [DHCR24] on days 9, 10, and 11 may contribute to the development of HFSC. However, the expression of this gene on day 11 was more than day 10 and on 10th day was more than day 9. Also, we assessed HFSC on day 14 and demonstrated these cells were positive for beta-? tubulin, and seladin-1 was not expressed in this day. HFSC express seladin-1 and this result demonstrates that these cells might be used to cell therapy for AD in future

Propagation of human germ stem cells in long-term culture

Spermatogonial stem cells [SSCs], a subset of undifferentiated type A spermatogonia, are the foundation of complex process of spermatogenesis and could be propagated in vitro culture conditions for long time for germ cell transplantation and fertility preservation. The aim of this study was in vitro propagation of human spermatogonial stem cells [SSCs] and improvement of presence of human Germ Stem Cells [hGSCs] were assessed by specific markers POU domain, class 5, transcription factor 1 [POU5F1], also known as Octamer-binding transcription factor 4 [Oct-4] and PLZF [Promyelocytic leukaemia zinc finger protein]. Human testicular cells were isolated by enzymatic digestion [Collagenase IV and Trypsin]. Germ cells were cultured in Stem-Pro 34 media supplemented by growth factors such as glial cell line-derived neurotrophic factor, basic fibroblast growth factor, epidermal growth factor and leukemia inhibitory factor to support self-renewal divisions. Germline stem cell clusters were passaged and expanded every week. Immunofluorecent study was accomplished by Anti-Oct4 antibody through the culture. The spermatogonial stem cells genes expression, PLZF, was studied in testis tissue and germ stem cells entire the culture. hGSCs clusters from a brain dead patient developed in testicular cell culture and then cultured and propagated up to 6 weeks. During the culture Oct4 were a specific marker for identification of hGSCs in testis tissue. Expression of PLZF was applied on RNA level in germ stem cells. hGSCs indicated by SSCs specific marker can be cultured and propagated for long-term in vitro conditions

vitro culture of human testicular stem cells on feeder-free condition

Spermatogonial stem cells are subpopulation of spermatogonial cells in testis tissue that support beginning and maintenance of spermatogenesis. Ubiquitin carboxy-terminal hydrolase L1 [UCHL1] could be a specific marker for identification of spermatogonial stem cells including spermatogonial sperm cells [SSCs] in testis tissue and during the culture; therefore we undertook this study to culture these human testicular stem cells [hTSCs] in vitro and approved the presence of human testicular stem cells [hTSCs] by UCHL1, also known as PGP9.5. Enzymatic digestion of human testicular biopsies was done by collagenase IV [4 mg/ml] and trypsin [0.25%]. Differential plating of testicular cells in DMEM/F12 and 10% FBS was applied for 16 hr. Floating cells were collected and transferred onto laminin-coated plates with Stem-Pro 34 media supplemented with growth factors of GDNF, bFGF, EGF and LIF to support self-renewal divisions; testicular stem cell clusters were passaged every 14 days for two months. Spermatogonial cells propagation was studied through Expression of UCHL1 in testis tissue and the entire testicular stem cell culture. Testicular stem cell clusters from 10 patients with obstructive azoospermia were cultured on laminin-coated plates and subsequently propagated for two months. The average of harvested viable cells was approximately 89.6%. UCHL1 was expressed as specific marker in testicular stem cells entire the culture. Human testicular stem cells could be obtained from human testicular tissue by a simple digestion, culturing and propagation method for long-term in vitro conditions. Propagation of these cells approved by specific marker UCHL1, during the culture period

[Interaction between vitamin A and pilocarpine on memory retention in adult male rats]

Several studies have reported that retinoic acid administration and/or consumption of a vitamin A-enriched diet could repair the aging induced memory deficits, decreased hippocampal long term potentiation [LTP]. Vitamin A deficiency impairs learning ability and hippocampal LTP in mice. In the present study, the effects of the vitamin A and pilocarpine [a muscarinic agonist] on memory retention in adult male rats were investigated. Post-training intracerebroventricular injections were carried out in all experiments. Memory retention was evaluated by using a step-through passive avoidance paradigm in adult male rats. Vitamin A [1000 and 2000 IU/rat] and pilocarpine [1 microg/rat] increased memory retention. The acetylcholine receptor agonist [pilocarpine] increased the response to vitamin A. The response to vitamin A was potentiated by pilocarpine. It is concluded that vitamin A elicits an interaction with the cholinergic system in memory retention

Involvement of the nucleus accumbensshell presynaptic NMDA receptors on anxiolytic-like behaviors induced by NMDA in adult male Wistar rat

Glutamatergic system stimulationthe nucleus accumbens shell, may affect anxiety-related behaviors, aversive learning and memory. Glutamate receptors are differentially distributed in pre- and postsynaptic sites contributing to neuronal communications.The present study aimed to examine the possible involvement of the NAc shell presynaptic NMDA receptors on NMDA induced responses, using the elevated-plus maze [EPM] task in maleWistar rats. Bilateral guide cannulae were implanted to allow microinjection of glutamatergic agonist [NMDA] or ca+2 channel blocker [SKF96365 hydrochloride] agents. Pretest intra-NAc shell infusion of NMDA induced anxiolytic-like behaviors and impaired the EPM-associated memory upon test and retest, respectively. In addition our findings showed that, the intra-NAc shell infusion of Ca+2 channel blocker at applied doses, does not alter the anxiety-like response and aversive memory upon test and retest, respectively. Furthermore, infusing the subthreshold dose SKF prior to the injection of effective doses of NMDA, reduced the anxiolytic-like response and improved the aversive memory impairment which had already been induced by intra-NAc shell NMDA injection. Our study showed that,inhibition of the neurotransmitter exocytosis from pre-synaptic neuron via Ca+2 channel blockade bySKF96365 decreases affected induced by NMDA in the NAc shell region, indicating the involvement of the pre-synaptic NMDA receptors in NMDA induced responses.Therefore, NMDA's ability to increase anxiolytic-like behaviors and the aversive memory impairment may be the result of an action on pre-synaptic glutamatergic receptors which in turn decrease the glutamate effect at synaptic terminal level

Influence of nitric oxide in the central amygdala on the acquisition and expression of morphine-induced place preference in morphine sensitized rats

Effects of intra-central amygdala administration of L-arginine, a nitric oxide precursor, and NG-nitro-L-arginine methyl-ester [L NAME], a nitric oxide synthase inhibitor, on the morphine-induced sensitization and also on the expression of morphine-induced place conditioning in rats were studied. Subcutaneous [s.c.] administration of morphine [2.5, 5 and 7.5 mg/kg] induced place conditioning. Repeated pretreatment of morphine [5 mg/kg, i.p.] followed by 5 days no drug treatment, increased place conditioning induced by morphine [0.5 mg/kg]. Repeated intra-central amygdala administration of L-arginine [0.3, 1 and 3 µg/ rat], with morphine during acquisition of sensitization, significantly increased or reduced morphine place conditioning in sensitized rats. The drug administration before testing also increased and reduced the expression of morphine place conditioning in sensitized animals. Repeated intra-central amygdala injections of L-NAME [0.3, 1 and 3 µg/rat] with morphine during acquisition of sensitization, reduced the acquisition of morphine place conditioning in the sensitized animals. The drug injection before testing also reduced morphine induced conditioning. The results indicate that nitric oxide [NO] within the central amygdala may be involved in the acquisition and expression of morphine place conditioning in morphine-sensitized rats

Bacteriorhodopsin and its mutants allude a breakthrough impending to artificial retina construction and strategies for curing blindness

Bacteriorhodopsin, a model system in nanobiotechnology, is a light-sensitive protein found in the archaean Halobacterium salinarum and a very identical protein to visual Rhodopsin. The modification of biological function of BR and its versatile properties is valuable for technical applications including the artificial retina. These photoactive elements of native and particular mutants of bacteriorhodopsin make protein films, used in artificial retinal implants, to treat some retinal diseases and disorders. The two major reasons of retinal photoreceptor cell deterioration are Age-related Macular Degeneration [AMD] and Retinitis Pigmentosa [RP]. As in vitro culture of Halobacterium is very difficult, and isolation procedure is much time consuming and usually inefficient, so genetic construction of protein is essential. Here, we have produced two types of bacteriorhodopsin, a native and a mutant BR [D85E] and studied their opto-electric responses with respect to wavelength and absorption properties. They are prerequisite for designing artificial retina [sensors] based on biomolecules. Therefore, the new promising technology soon will conceivably eradicate the blindness

[Protective effect of walnut [juglans regia L.] extract against CCI[4] - induced hepatotoxicity in rats]

Walnut [Juglans regia L.] is widely distributed all over the world. Dry seeds, [nuts], as well as green walnuts, shells, bark, green husks [epicarps] and leaves, have all been used in the cosmetic and pharmaceutical industries. In the present study, hepatoprotective potential of ethanolic extract of walnut leaves was investigated against carbon tetrachloride [CCl [4]] induced liver damage in rats. This experimental study was done on 36 rats divided into six groups. Adult male rats were orally administered different doses of walnut extract [50, 100, 200 and 400 mg/kg bw/daily] along with CCl [4] [50% CCl [4], in olive oil, 1 ml/kg, intrapertioneally] twice a week for 28 consecutive days. Biochemical parameters like alanine amino transferase, aspartate amino transferase, alkaline phosphatase and total protein levels in the serum were determined. Statistical analysis was carried out using ANOVA test. Administration of CCl [4] increased the serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase [p<0.01]. Treatment with the ethanolic extract of walnut leaves significantly decreased the above parameters [p<0.01]. Ethanolic extract of walnut leaves could protect liver against the CCl [4]-induced oxidative damage in rats, and this hepatoprotective effect might be due to modulation of toxic and oxidant enzymes and also to the scavenger effect on free radicals

Seminal plasma levels of copper and its relationship with seminal parameters

The trace element copper has been identified as a highly toxic element for sperm. It is known to affect sperm motility in humans, and experimental implantation of copper in the epididymis, vas deferens, and scrotum of mammals has been demonstrated to affect fertility detrimentally. Sperm concentration, motility, vitality and morphology are parameters used to evaluate potential male fertility. Since, copper is believed to be important for spermatogenesis; we conducted a study to investigate the correlation between seminal plasma copper concentration and human semen parameters in 232 males. We selected 232 subfertile or infertile men who referred to Omid Fertility Clinic, randomly. Samples were categorized into normospermic [n=32], oligozospermic [n=73], asthenozospermic [n=111] and azospermic [n=16] groups according to their spermiogrames. Total seminal plasma copper concentration was determined by furnace atomic absorption spectrophotometer. The results showed that seminal plasma copper concentrations in oligozospermic, asthenozospermic and azospermic groups are significantly higher than normozospermic group [p<0.01]. Also, negative correlations were found between seminal plasma copper concentration and sperm count [p<0.05], sperm motility [p<0.01], sperm vitality [p<0.01], normal morphology [p<0.01] and pH [p<0.01] in all groups. It was suggested that excess copper in seminal plasma was detrimental for male reproductive capacity by reducing sperm count, motility, vitality and morphology

Anti-inflammatory effect of ethanolic extract and essential oil of eucalyptus globulus in mice

Inflammation is a mechanism involving a complex series of events including dilatation of arterioles, venules and capillaries with increased vascular permeability, exudation of fluids including plasma proteins and leukocyte migration into the inflammatory area. In the present study, the anti-inflammatory effects of Eucalyptus globulus alcoholic extract and essential oil leaves were studied in NMRI mice. In this experimental study, 15 minutes after intra-peritoneal injection of the ethanolic extract [50, 100 and 200 mg/kg, i.p.], essential oil [0.1, 0.4, 0.5 ml/kg, i.p.] and dexamethasone [10 mg/kg, i.p.], 0.03 ml of xylene was applied to the anterior surface of the right ear of NMRI mice. The left ear was considered as control. Two hours after xylene application, mice were sacrificed and both ears removed. The effect on acute inflammation was assessed using vascular permeability increased by xylene-induced ear edema in mice. Alcoholic extract of Eucalyptus globulus with doses 100 and 200 mg/kg and essential oil leaves of Eucalyptus globulus with doses of 0.4 and 0.55 ml/kg showed significant and dose-dependent anti-inflammatory activity against acute inflammation induced by xylene ear edema test. Its anti-inflammatory effects were similar to dexamethason. The present study indicated that Eucalyptus globule has anti-inflammatory effect on mice and should be considered in future therapeutic studies

[Hypoglycemic effect of alcoholic extract of eucalyptus [Eucalyptus globulus L.] leaves in healthy and diabetic rats]

In traditional medicine, leaves of eucalyptus [Eucalyptus globules L.] possess interesting biological behavior, such as antioxidation, antibacterial and antiviral activities. The aim of this study was to evaluate hypoglycemic effect of alcoholic extract of eucalyptus [Eucalyptus globulus L.] leaves in healthy and diabetic rats. In this experimental study, the effects of oral administration of 0.05, 0.1, 0.2 and 0.4 g/kg body weight of eucalyptus leaves alcoholic extract for 21 days on the glucose and insulin levels in healthy and streptozotocin-induced diabetic rats were evaluated. A comparison was made between the effect of the alcoholic extract and a known antidiabetic drug, glibenclamide [600 mg/kg body weight]. The results showed that orally administration of the eucalyptus alcoholic extract decreased significantly the serum glucose levels, whereas it increased serum insulin in diabetic but not in normal rats [p<0.05]. The extract could not change the level of serum glucose and insulin in normal rats significantly. The hypoglycemic effect of the extract was similar to that observed by glibenclamide. The eucalyptus alcoholic extract can serve as a good adjuvant in the present armamentarium of antidiabetic drugs. Further biochemical and pharmacological investigations should be carried out to elucidate in details the mechanism of action of this plant

Insulin receptor gene mutations in Iranian patients with type II diabetes mellitus

Patients with diabetes mellitus type II suffer from hyperglycemia because they are not able to use the insulin that they produce, often due to inadequate function of insulin receptors. There are some evidences that this deficiency is inherited in a dominant autosomal manner and leads to the malfunction of the pancreatic beta cells resulting in insulin excretion disorders. In this study, we sought to identify mutations in the insulin receptor [INSR] gene, which can cause insulin resistance in type II diabetic patients. DNA was extracted from peripheral blood cells of the patients [n = 128] diagnosed with type II diabetes. All 22 exons of the INSR gene of the patients were analyzed for mutations running PCR, conformation-sensitive gel electrophoresis and DNA sequencing, consecutively. Approximately 26% of the patients had genetic mutations; however, most of them were not reported. These mutations include exon 2 [His171Asn, Ile172Ser, Cys196Ser and Ser210Arg], exon 3 [Gly227Asp and Gly232Ser], exon 8 [Thr543Ser], exon 9 [a heterozygote was observed with no change in phenylalanine at position 669], exon 13 [two heterozygotes: Arg890Pro with Asn865 remaining unchanged], exon 14 [Ala906Gly and Pro918Trp with Arg902 unchanged], exon 17 [Val1086Glu] and exon 19 [His1157Gln with Thr1172 unchanged]. The lack of similar mutation records in literature and genetic data banks may suggest a geographic pattern for these INSR gene variants in our population

[Antinociceptive effects of ethanolic extract of parsley [Petroselinum crispum L.] leaves in mice]

Pain is a sensorial modality, which in many cases represents the only symptom for the diagnosis of several diseases. Du to addictive properties and side effects of morphine, there is less attention to use it. Medicinal plants are used increasingly in the treatment of painful illnesses. The aim of this study was to evaluate the analgesic activity of ethanolic extract of parsley leaves in mice. In this experimental study, analgesic activity of ethanolic extract of parsley leaves was evaluated in mice by formalin test and acetic acid test. Ethanolic extract of parsley leaves [at doses 100, 150 and 200 mg/kg] and morphine [10 mg/kg], as a standard drug, were injected intraperitoneally. The control group was administered saline as vehicle of ethanolic extract. Ethanolic extract of plant decreased both phases of pain in formalin test. Also, it decreased number of abdominal muscle contraction in Writhing test. The present study indicated that ethanolic extract of parsley leaves has analgesic effects on mice and further studies need to evaluate its clinical properties