The effect of cold atmospheric plasma (NO) alone and in combination with NPH insulin on the full-thickness excisional wound healing in a diabetic rat model.

This study was planned to investigate an alternative treatment modality in diabetic wound healing. In this experimental study, the efficacy of both cold atmospheric plasma/nitric oxide (NO) and NPH insulin ointment, recently known to have beneficial effects on wound healing, was investigated in diabetic wound healing. Twenty-four (24) diabetic rats were divided into four groups DC, DI, DNO and DINO (diabetic control, diabetic insulin, diabetic nitric oxide, diabetic insulin + nitric oxide groups). No treatment was applied to the DC group, NPH insulin was applied to the DI group, CAP/NO was applied to the DNO group, and CAP/NO + NPH insulin was applied to the DINO group once daily for 14 days. The wound area reduction and the wound contraction rate were calculated on the basis of the tissue sections taken, and histopathological and genetic analyses were carried out. Compared to the control group, exogenous NO gas was found to be a potent antibacterial agent in the diabetic wound healing, causing a reduction in the wound area (P = 0.034), an increased contraction rate (P = 0.021), epithelialisation (P = 0.02), collagen organisation (P = 0.006) and a reduction in the number of inflammatory cells (P = 0.002). A significant increase in the expression of IL-8 mRNA was observed (P = 0.026). It was concluded that NPH insulin alone contributes to wound healing, but it is not necessary to use it together with exogenous NO gas.

The effect of co-administration of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rat liver.

It is possible to use plant-derived antioxidant molecules in the form of dietary supplements. However, dietary supplement-drug interaction pattern has not been well defined for most of these products. The aim of this study was to determine the effects of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rats. Streptozotocin was administered to create experimental diabetes. Resveratrol (5 mg/kg) (R), glibenclamide (5 mg/kg) (G), and berberine (10 mg/kg) (B) were administered individually or in combinations in DMSO by intraperitoneal administration route to the diabetic rats. DMSO was also given to non-diabetic control (C) and diabetic control (D) groups. Livers of rats were taken under anesthesia at the end of the treatment period (12 days). Ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), aniline 4-hydroxylase (A4H), erythromycin N-demethylase (ERND), glutathione S-transferase (GST), catalase (CAT), and glutathione reductase (GR) activities were measured in microsomes and cytosols. In addition, histomorphological studies were also performed in the liver tissues. EROD activity of D+R was significantly higher than C and D+R+B. PROD activity of D+R was significantly higher than C, D, D+R+G, D+R+B, and D+R+B+ G. PROD activity of D+B was significantly higher than C and D+R+B. ERND activity of D+R was significantly higher than D+R+G and D+R+B. GST activity of D+R was significantly higher than D+R+G. CAT activity of D+B was significantly lower than C. It is clear that co-administration of resveratrol, berberine, and glibenclamide modifies some of the important xenobiotic metabolizing enzyme activities. Resveratrol and berberine have the potential to cause dietary supplement-drug interaction.

Modulation of xenobiotic metabolizing enzyme activities in rat liver by co-administration of morin, endosulfan, and 7,12-dimethylbenz[a]anthracene.

Morin is a flavonoid which is present in many plants. Endosulfan and 7,12-dimethylbenz[a]anthracene (DMBA) are toxic chemicals that humans are exposed to in their daily lives. In this study, the protective role of morin was investigated in endosulfan and DMBA treated rats. Eight groups, each comprising seven 2.5-month-old adult male Wistar rats (weighing 170-255 g), were used. Endosulfan, morin, and DMBA were administered individually or in combinations, at 5 mg/kg body weight (bw) (three times/week), 25 mg/kg bw (three times/week), and 30 mg/kg bw (once/week for three weeks) via oral gavage, respectively. On day 54 of the administration period, the rats were killed. DMBA + endosulfan co-administration significantly increased CYP1A1-, CYP1A2-, CYP2E-, and GST-associated activities in the rats compared to the control. DMBA + endosulfan + morin significantly increased CYP1A1, CYP1A2, CYP3A, and GST associated activities in the rats relative to the control. Histopathological studies were performed to investigate protective effects of morin on liver damage. The results indicated that DMBA + endosulfan treatment induced liver damage, and morin reduced this damage. These findings suggest that CYP1A, CYP3A, and GST enzyme activities participate in the protective mechanism of morin against endosulfan and DMBA induced toxicity.

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats.

The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo meningeal preparations in rats. Rats were intraperitoneally administered saline, GTN (10 mg/kg), vehicle, saline + GTN, SC (50 µg/kg) + GTN, and SC alone. Also, ex vivo meningeal preparations were applied topically 100 µmol/L GTN, 50 µmol/L SC, and SC + GTN. Calcitonin gene-related peptide (CGRP) contents of plasma, trigeminal neurons and superfusates were measured using enzyme-immunoassays. Dural mast cells were stained with toluidine blue. c-fos neuronal activity in trigeminal nucleus caudalis (TNC) sections were determined by immunohistochemical staining. The results showed that GTN triggered the increase in CGRP levels in plasma, trigeminal ganglion neurons and ex vivo meningeal preparations. Likewise, GTN-induced c-fos expression in TNC. In in vivo experiments, GTN caused dural mast cell degranulation, but similar effects were not seen in ex vivo experiments. Salmon calcitonin administration ameliorated GTN-induced migraine pain by reversing the increases induced by GTN. Our findings suggested that salmon calcitonin could alleviate the migraine-like pain by modulating CGRP release at different levels including the generation and conduction sites of migraine pain and mast cell behaviour in the dura mater. Therefore salmon calcitonin may be a new therapeutic choice in migraine pain relief.

Vasoactive Intestinal peptide modulates c-Fos activity in the trigeminal nucleus and dura mater mast cells in sympathectomized rats.

Neurogenic inflammation in the dura mater caused by trigeminal nociceptive activation has been implicated in the pathophysiology of migraine. Vasoactive intestinal polypeptide (VIP) is a powerful neuroprotective neuropeptide that can modulate mast cell behavior. Migraine is also associated with sympathetic insufficiency. This study investigates the effects of VIP on the number of mast cells in the dura mater and on c-Fos expression in the trigeminal nucleus of sympathectomized rats. Experiments were carried out with 32 Sprague-Dawley male rats with body weights of 200-250 g. In the sympathectomized group, the left superior cervical sympathetic ganglion was removed. In the sympathectomized + VIP group, postoperative VIP 25 ng/kg/day (0.2 ml) was administered for 5 days. In the sham group, the ganglion and nerves were exposed but not dissected. Dura maters were stained with toluidine blue, and brainstems were labeled by indirect immunohistochemistry for c-Fos. Sympathectomy significantly increased the number of mast cells in both the ipsilateral and the contralateral dura mater (P < 0.001). VIP decreased the number of mast cells in both sides of the dura mater in sympathectomized rats. VIP also decreased c-Fos expression in the ipsilateral trigeminal nucleus of sympathectomized rats (P < 0.001). In the context of an experimental superior cervical ganglionectomy model of migraine, VIP is an efficient modulator of neurogenic inflammation of the dura.

Inhibitory effects of topical cyclosporine A 0.05% on immune-mediated corneal neovascularization in rabbits.

BACKGROUND: We aimed to study the inhibitory effects of topical cyclosporine A (CsA) 0.05% on immune-mediated corneal neovascularization, and to compare its efficacy with those of dexamethasone 0.1% and bevacizumab 0.5%. METHODS: Immune-mediated corneal neovascularization was created in 36 right eyes of 36 rabbits. The rabbits were then randomized into four groups. Group I received CsA 0.05%, Group II received dexamethasone 0.1%, Group III received bevacizumab 0.5%, and Group IV received isotonic saline twice a day for 14 days. The corneal surface covered with neovascular vessels was measured on the photographs. The rabbits were then sacrificed and the corneas excised. Paraffin-embedded sections were stained with hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. RESULTS: The means of percent area of corneal neovascularization in Group I, II, III, and IV were 24.4%, 5.9%, 37.1%, and 44.1%, respectively. The inhibitory effect of CsA 0.05% was found to be better than the effect found in the bevacizumab 0.5% and control groups (p = 0.03 and p = 0.02, respectively). CsA 0.05% was found to have significantly lesser inhibitory effects on corneal neovascularization than dexamethasone 0.1% (p < 0.001). Apoptotic cell density was higher in Group III and Group IV than in Group I and Group II. There was no difference between Group I and Group II in terms of apoptotic cell density (p = 0.7). CONCLUSIONS: Topical CsA 0.05% was shown to have an inhibitory effect on immune-mediated corneal neovascularization in rabbits.

Effects of Coriandrum sativum on distant organ inflammation and apoptosis due to liver ischemia/reperfusion injury.

Liver ischemia/reperfusion (IR) often affects distant organs, such as small intestine, kidney, and lung. Coriandrum sativum (CS) has an antioxidant and anti-inflammatory effect on liver damage. The aim of this study was to investigate the anti-inflammatory and antiapoptotic effects of CS extract on small intestine, lung, and kidney after the liver IR injury. Small intestine, lung, and kidney tissues were evaluated and scored in terms of cell degeneration, inflammation, and congestion, as well as caspase-3 (Cas-3) and cluster of differentiation 31 (CD31) immunostainings were carried out. Renal enzymes, creatinine and urea levels were measured biochemically in serum. After IR, a decrease in villi size, diffuse degeneration, epithelial cell shedding and extensive congestion in the capillaries were observed. Meanwhile, the number of degenerated villi and congestion decreased in the IR+CS group. Due to IR, increased congestion was detected in the interalveolar septum of the lungs and in the capillaries between the kidney tubules. It was also observed that the positively stained cells with Cas-3 and CD31 were increased in the lung, kidney, and small intestine tissues of the IR group, and decreased in the IR+CS group. Kidney enzymes, urea and creatinine levels were significantly increased in the IR group and decreased in the IR+CS group. In conclusion, it was observed that liver IR caused changes in distant organs, especially in the small intestine, lung, and kidneys. Damaging effects of IR as well as apoptosis and inflammation were found to be decreased in the groups treated with CS.

Cytotoxic effects of nasal buserelin on nasal mucosal tissue in rabbits.

To investigate the cytotoxic effects of nasal buserelin on rabbit nasal mucosal tissue, twenty-four female rabbits were studied prospectively. The rabbits were divided into 4 groups including 6 rabbits. The rabbits' left noses were included in the all study groups: 150 µg/puff/day of buserelin acetate was administered topically twice daily during 21, 42 and 63 days. Saline was administered topically twice daily to the left nasal cavity in the control group. The nasal septal mucosal stripe tissue was carefully removed from underlaying cartilage after sedation. HE staining, Masson's trichrome, toluidine blue and TUNEL staining were used to evaluate mucosal changes. Each preparation was investigated via apoptotic cells, and they were accounted. Kruskal-Wallis test was used to evaluate nonparametric comparison of apoptotic cells. Mononuclear cells have been raised in the sub-epithelial connective tissue, nucleuses of epithelial cells in the apical region were pyknotic, and apoptotic cells were determined on 21-day group. In the 42-day group, nasal epithelial tissue was similar to 21-day group and epithelial cells including pyknotic nucleus were present in this group, too. In the 63-day group, epithelial cells were light colored. Venous sinuses in the sub-epithelial connective tissue were wide but not congested and not raised collagen filaments. In the intra-epithelial tissue, some of cells were TUNEL (+). Apoptotic cells were fewer in the control group according to 21-day group. In 42- and 63-day groups, these cells were fewer than in 21-day group. Numerical difference was present between the groups, but statistical significance was not found between the groups. We concluded that nasal buserelin cytotoxicity was not potent in the nasal cavity in rabbits. We use nasal buserelin in all indications with confidence.

Effects of Probiotic Bacteria on Central Neuronal Activation in Experimental Colitis.

BACKGROUND: Brain-gut axis dysregulation is observed in inflammatory bowel disease. However, the effect of altered gut flora on neuro- immunomodulation and its role in the pathogenesis of inflammatory bowel disease are unknown. The aims of this study are to determine (i) whether colitis modifies the expression of c-fos, a marker of general neuronal activation in the brain and (ii) whether this activation could be modulated by probiotic bacteria. METHODS: In this study, 28 Sprague-Dawley rats were divided into 4 groups: colitis-probiotic group, non-colitis-fed-control group receiv- ing probiotic Lactobacillus delbrueckii subsp. Bulgaricus B3 strain for 7 days, colitis group, and sham group receiving only sodium chlo- ride. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid-ethanol. The expression of c-fos was detected by immunohistochemistry in the brain tissue. Cytokines and inflammatory mediators were analyzed in the plasma. Histological scores and oxidative status were analyzed in the colon samples. RESULTS: The inflammatory response was accompanied by increased levels of cytokines, lipid peroxidation activities, c-fos expression in the medial nucleus of the amygdala, and decreased levels of antioxidant enzymes in the colitis (P < .001). Probiotic treatment reversed those effects. Also, histopathologic scores were significantly lower in the probiotic-treated groups compared to the colitis group (P = .035). In contrast, the expression of c-fos was significantly increased in the paraventricular nucleus of hypothalamus in the probiotic- treated rats (P < .001). CONCLUSION: Colitis and intestinal inflammation are associated with the activation of neurons in the limbic system creating stress-like effects in the brain. Probiotics diversely modulate limbic response and hypothalamic axis activity in addition to protective effects in inflammation.

Dietary vitamin C and E modulates oxidative stress induced-kidney and lens injury in diabetic aged male rats through modulating glucose homeostasis and antioxidant systems.

Diabetes induces oxidative stress in aged human and rat, although daily supplementation of vitamins C and E (VCE) can be beneficial to aged diabetic rats by reducing free radical production. The aim of the present study was to evaluate whether dietary VCE supplementation relieves oxidative stress in streptozotocin (STZ)-induced diabetic in aged rats. Thirty aged rats were randomly divided into three groups. The first group was used as a control. The second group was made diabetic using a single dose of intraperitoneal STZ. VCE-supplemented feed was given to aged diabetic rats constituting the third group. On the 21st day of the experiment, blood, lens and kidney samples were taken from all animals. Glutathione peroxidase (GSH-Px) activity in lens and kidney, reduced glutathione (GSH), vitamin E and ß-carotene concentrations in kidney were lower in the diabetic group than in the control whereas plasma glucose, urea and creatinine, and kidney and lens peroxidation (LP) levels were higher in the diabetic group than in the control. However, kidney and lens LP levels, and plasma glucose, urea and creatinine values were decreased by VCE supplementation. Lens and kidney GSH-Px activity, kidney GSH, vitamin E and ß-carotene concentrations and erythrocyte counts were increased by VCE treatment. Kidney weights, vitamin A, haemoglobin, hematocrit, leukocyte and platelets values were not changed by diabetes and/or VCE supplementation. VCE ameliorated also diabetes-induced histopathological changes in kidney. In conclusion, we observed that VCE supplementation is beneficial towards kidney and lens of aged diabetic rats by modulating oxidative and antioxidant systems.

Protective effects of CAPE on liver injury induced by CCL4: an electron microscopy study.

This study was designed to investigate the protective effects of caffeic acid phenethyl ester on carbon tetrachloride-induced liver damage in rats. Twenty-four male Wistar rats were divided in three groups. Group I was used as control. Rats in group II were injected with carbon tetrachloride every other day for 1 month, whereas rats in group III were injected with carbon tetrachloride and caffeic acid phenethyl ester every other day for 1 month. At the end of the experiment, all animals were killed by decapitation and their livers were removed. Liver tissues were processed for electron microscopy. Histopathologically, hepatocytes of rats treated with carbon tetrachloride had damage in the cytoplasmic organelles and nuclei membranes as well as an excessive lipid accumulation in the hepatocytes. However, those histopathological changes were reduced with the coadministration of carbon tetrachloride and caffeic acid phenethyl ester. We conclude that caffeic acid phenethyl ester treatment has the capability to prevent carbon tetrachloride-induced liver damage in rats.

Carvacrol treatment opens Kir6.2 ATP-dependent potassium channels and prevents apoptosis on rat testis following ischemia-reperfusion injury model.

Testicular torsion is a urological problem that causes subfertility and testicular damage in males. Testis torsion and detorsion lead to ischemia-reperfusion (IR) injury in the testis. Testicular IR injury causes the increase of reactive oxygen species (ROS), oxidative stress (OS) and germ cell-specific apoptosis. In this study, we aimed to investigate whether Carvacrol has a protective effect on testicular IR injury and its effects on Kir6.2 channels, which is a member of adenosine triphosphate (ATP)-dependent potassium channels. In the study, 2-4 months old 36 albino Wistar rats were used. For experimental testicular IR model, the left testis was rotated counterclockwise at 720° for two hours, and after two hours following torsion, detorsion was performed. Carvacrol was dissolved in 5% Dimethyl Sulfoxide (DMSO) at a dose of 73 mg∕kg and half an hour before detorsion, 0.2 mL was administered intraperitoneally. In testicular tissues, caspase 3 and Kir6.2 immunoexpressions were examined. Serum malondialdehyde (MDA) and testosterone levels were measured. Apoptotic cells and serum MDA levels were significantly decreased and Kir6.2 activation was significantly increased in Carvacrol-administrated IR group. As a result of our study, Carvacrol may activates Kir6.2 channels and inhibits apoptosis and may have a protective effect on testicular IR injury.

Effects of adipose tissue-derived stromal vascular fraction on osteochondral defects treated by hyaluronic acid-based scaffold: An experimental study.

OBJECTIVES: This study aims to evaluate the effect of adipose-derived stromal vascular fraction (SVF) on osteochondral defects treated by hyaluronic acid (HA)-based scaffold in a rabbit model. MATERIALS AND METHODS: Eighteen white New Zealand rabbits were randomly grouped into the experimental group (n=9) and control group (n=9). In all groups, osteochondral defects were induced on the weight-bearing surfaces of the right femoral medial condyles, and a HA-based scaffold was applied to the defect area with microfractures (MFs). In this study, 1 mL of adipose-derived SVF was injected into the knee joints of the rabbits in the experimental group. For histological and macroscopic evaluation, four rabbits were randomly selected from each group at Week 4, and the remaining rabbits were sacrificed at the end of Week 8. Macroscopic assessments of all samples were performed based on the Brittberg scoring system, and microscopic evaluations were performed based on the O'Driscoll scores. RESULTS: Samples were taken at Weeks 4 and 8. At Week 4, the O'Driscoll scores were significantly higher in the control group than the experimental group (p=0.038), while there was no significant difference in the Brittberg scores between the two groups (p=0.108). At Week 8, the O'Driscoll score and Brittberg scores were statistically higher in the experimental group than in the control group (p=0.008 and p=0.007, respectively). According to the microscopic evaluation, at the end of Week 8, the cartilage thickness was greater in the experimental group, and nearly all of the defect area was filled with hyaline cartilage. CONCLUSION: Application of adipose-derived SVF with MF-HA-based scaffold was better than MF-HA-based scaffold treatment in improving osteochondral regeneration. Therefore, it can be used in combination with microfracture and scaffold to accelerate cartilage regeneration, particularly in the treatment of secondary osteoarthritis.

The Potential Therapeutic Effects of Agmatine, Methylprednisolone, and Rapamycin on Experimental Spinal Cord Injury.

OBJECTIVE: In spinal cord injury (SCI), the primary mechanical damage leads to a neuroinflammatory response and the secondary neuronal injury occurs in response to the release of reactive oxygen species (ROS). In addition to the suppression of inflammation, autophagy plays a significant role in the survival of neurons during secondary SCI. The present study aimed to examine the anti-inflammatory and autophagic effects of agmatine and rapamycin in SCI and to compare the results with methylprednisolone (MP) used in the clinic. MATERIALS AND METHODS: In this animal-based experimental study, thirty adult male Sprague-Dawley rats were randomly divided into five groups as sham-control, injury, injury+MP, injury+rapamycin, injury+agmatine groups. SCI was induced by compressing the T7-8-9 segments of the spinal cord, using an aneurysm clip for one minute, and then rats were treated daily for 7 days. Seven days post-treatment, damaged spinal cord tissues of sacrificed rats were collected for microscopic and biochemical examinations using histopathologic and transmission electron microscope (TEM) scores. Malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were spectrophotometrically measured. RESULTS: The results of this study showed that the damaged area was smaller in the rapamycin group when compared to the MP group. Many autophagic vacuoles and macrophages were observed in the rapamycin group. Degeneration of axon, myelin, and wide edema was observed in SCI by electron microscopic observations. Fragmented myelin lamellae and contracted axons were also noted. While MDA and GPx levels were increased in the injury group, MDA levels were significantly decreased in the agmatine and MP groups, and GPx levels were decreased in the rapamycin group. CONCLUSION: The results of our study confirmed that rapamycin and agmatine can be an effective treatment for secondary injury of SCI.

The preventive effect of low molecular weight heparin on CCL4-induced necrosis and apoptosis in rat liver.

INTRODUCTION: Heparin having anti-inflammatory and anti-fibrotic properties may have therapeutic effect on liver injury. The present study investigated the effect of low molecular weight heparin (Enoxaparin) on carbon tetrachloride (CCl4) induced hepatic necrosis and apoptosis in rats. MATERIAL AND METHODS: Thirty male rats were divided into 5 groups. Group I: Control; Group II: Olive oil dissolved CCl4 at dose of 1 mL/kg, ip, twice per week; Group III: CCl4 and Enoxaparin at dose of 180 IU/kg, sc, daily; Group IV: Enoxaparin; Group V: Olive oil at dose of 1 mL, ip, twice per week. The liver histology at the forth week was examined by haematoxylin-eosin, Masson.s trichrome, Toluidine blue and Periodic acid schiff stains. Proliferative and apoptotic activities were assessed semi-quantitatively by proliferating cell nuclear antigen (PCNA) and caspase-3 immune staining and TUNEL method. Semi-quantitative values formulated by the equation HSCORE =ΣP(i) (i+1) including both distribution and intensity of staining. Additionally, nidogen and a-smooth muscle actin were labeled by immunohistochemistry. RESULTS: CCl4 group had marked hepatocelluar necrosis around the vena centralis and increased inflammatory cells and mast cells. Hepatocytes showed deposition of lipid droplets, decrease in glycogen, apoptosis, and picnotic or enlarged nuclei. Enoxaparin reduced necrosis, apoptosis, and number of mast cells but had no effect on lipid droplets in hepatocytes. HSCORE.s of caspase-3 and PCNA were also significantly decreased by administration. CONCLUSION: Enoxaparin have beneficial effects against necrosis as well as apoptosis at the early stage of CCL4 induced liver injury.

The effect of pinealectomy and leptin hormone on the proliferation and apoptosis activation in Syrian hamster testis in different photoperiods.

The effects of pinealectomy and leptin hormone on proliferative and apoptotic processes in the epithelia of testicular seminiferous tubules of Syrian hamsters have been investigated. Proliferative and apoptotic processes were assessed semi-quantitatively by proliferating cell nuclear antigen (PCNA) and caspase-3 immune stainings. Animals used in the study were divided into four groups; control, pinealectomy (PinX), leptin-treated (10 microg/mL/day/kg body weight, intraperitoneally) and pinealectomy + leptin groups. Half of the hamsters in each group were exposed to short and the other half to long photoperiods for 8 weeks. In short photoperiod, PCNA activity especially in spermatogonia was significantly higher in the pinealectomy and leptin-treated groups compared with the control group. Histological score (HSCORE) value of PCNA in the PinX + leptin group was lower than those of PinX and leptin-treated groups. HSCORE value of caspase-3 in PinX and PinX + leptin groups was increased. In the long photoperiod, PCNA activation in the PinX group was significantly lower than the control group while the differences between the controls and other groups were not significant. The difference between the increases in caspase-3 activity in the PinX and control groups was significant. Thus, it was observed that photoperiods had no effect on the proliferation activity in the control groups. The inhibiting effect of short photoperiod on testis was not observed throughout 8 weeks. PinX eliminated the inhibiting effect of short photoperiod but did not alter the stimulating effect of long photoperiod. Leptin did not show any effect in long photoperiod but decreased proliferation by stimulating melatonin in short photoperiod.

The effect of ethanol intake on tendon healing: a histological and biomechanical study in a rat model.

INTRODUCTION: Ethanol has a suppressive effect on inflammation and the immune system, but the effect of ethanol on tendon healing in vivo has not been studied. The purpose of this study was to investigate the histological and biomechanical effects of ethanol intake on tendon healing in a rat tendon injury model. MATERIALS AND METHODS: Forty-seven rats were randomly assigned to either ethanol or control groups. Progressively increasing concentrations of ethanol combined with glucose were administered to these rats in their drinking water. After 1 week, the Achilles tendon of each rat was injured proximal to its insertion on the calcaneus. All rats were euthanized at 4 weeks. The tendons were evaluated both histologically and biomechanically. The histologic examination of these tendons was done using a semi-quantitative 4-point scale to rate cell morphology, the degree of ground substance staining, collagen organization, and vascular changes. Load to failure (N) strength was obtained with biomechanical testing. RESULTS: Tendon failure loads were lower in the ethanol group (31.6 +/- 8.8 N) than in the control group (39.7 +/- 8.2 N) (P = 0.04). Histologic tenocyte scores were higher in the ethanol group (1.90 +/- 0.73) than the control group (0.9 +/- 0.73) (P = 0.01). CONCLUSION: Ethanol ingestion resulted in abnormal tenocyte morphology, disorganized collagen bundles with a tendency toward increased tenocyte number, and neovascularization 3 weeks after the tendon injury indicating delayed and abnormal healing. The healing tendons in the alcohol treated group failed at statistically lower loads than the control group.

The Effect of L-Carnitine on Cadmium Toxicity in Liver and Kidney Tissue in Prepubertal Female Rats / Efecto de la L-Carnitina sobre la Toxicidad del Cadmio en el Hígado y el Tejido Renal en Ratas Hembras Prepúberes

SUMMARY: Cadmium (Cd) is a toxic element that accumulates in kidney and liver. L-carnitine(LC) is a natural compound that has been shown to exhibit antioxidant activity. Aim of this study was to investigate the effect of L-carnitine against cadmium-induced changes in liver and kidney tissues in prepubertal female rats. In this study 21-day-old female Wistar Albino rats were used. Control, cadmium (2 mg/kg cadmium intraperitoneally), L-carnitine (300 mg/kg orally) and cadmium+L-carnitine groups were formed. Liver and kidney tissue sections were stained with Hematoxylin-Eosin and Masson Trichrome. Histological scoring was performed in liver and kidney. In the liver tissue given Cd, bile duct proliferation, inflammation cells and connective tissue in the portal area were decreased in treatment group. In kidneys, cadmium group treated with L-carnitine, it was observed that the capillary congestion in the kidneys decreased, but tubular dilatation continued in some places. In fibrosis scoring of the liver groups,statistically significant decrease was observed in the Cd+LC group compared to group of cadmium. In the histological scoring results of the kidney groups, statistically significant decrease in congestion and tubular epithelial degeneration was observed in the group treated with L-carnitine compared to group with cadmium. In conclusion medium-dose cadmium has toxic effects in liver and kidney of prepubertal female rats in subacute period,these effects are alleviated with L-carnitine.

El cadmio (Cd) es un elemento tóxico que se acumula en los riñones y el hígado. La L-carnitina (LC) es un compuesto natural que ha demostrado tener actividad antioxidante. El objetivo de este estudio fue investigar el efecto de la L-carnitina contra los cambios inducidos por el cadmio en los tejidos del hígado y el riñón en ratas hembra prepúberes. En este estudio se utilizaron ratas Wistar Albinas hembra de 21 días de edad. Se formaron grupos control, cadmio (2 mg/kg de cadmio por vía intraperitoneal), L- carnitina (300 mg/kg por vía oral) y cadmio + L-carnitina. Se tiñeron secciones de tejido de hígado y riñón con Hematoxilina-Eosina y tricrómico de Masson. La puntuación histológica se realizó en hígado y riñón. En el tejido hepático que recibió Cd, la proliferación de los conductos biliares, las células inflamatorias y el tejido conectivo en el área portal disminuyeron en el grupo con tratamiento. En los riñones, en el grupo de cadmio tratado con L- carnitina, se observó que la congestión capilar disminuyó, pero la dilatación tubular continuó en algunos sitios. En la puntuación de fibrosis de los grupos de hígado, se observó una disminución estadísticamente significativa en el grupo de Cd+LC en comparación con el grupo de cadmio. Los resultados de puntuación histológica de los grupos de riñón, arrojó una disminución estadísticamente significativa en la congestión y el epitelio tubular Se observó degeneración en el grupo tratado con L-carnitina en comparación con el grupo con cadmio. En conclusión, las dosis medias de cadmio tienen efectos tóxicos en el hígado y los riñones de ratas hembras prepúberes en el período subagudo; estos efectos se alivian con L-carnitina.

4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-ß-D-glucopyranoside effect in liver regeneration.

Following an injury or resection, the mammalian liver has the capacity to regain its former volume and functioning by restoring itself. Studies have demonstrated that antioxidants play a role in hepatic regeneration. This study investigated the effect of 4-(3,4-dihydroxybenzoyloxymethyl) phenyl-O-ß-D-glucopyranoside (PG) obtained from Origanum micranthum on liver regeneration. Sixty Wistar Albino rats were used. In the sham-operated group, a midline abdominal laparotomy was performed without hepatectomy. In the partial hepatectomy (PHx) group, the median and left lateral lobes were removed. Rats in the PHx group received 20 mg/kg/day PG intraperitoneally before being sacrificed at 24, 48, and 72 hrs, and 7 days later. Liver tissues were collected for immunohistochemical analysis and electron microscopic evaluation. We found an increase in mitotic index, and the numbers of Ki-67 stained hepatocytes in all PHx early stage groups (24 hr, 48hr, 72 hr), but not in 7-day groups. The regeneration mediators eNOS, iNOS, TNF-α and NF-κB were shown to increase in PHx groups. This increase was more prominent dependening on time. In the PHx treatment (PHx+PG) groups, while eNOS was still high, iNOS, TNF-α and NF-κB had decreased. The apoptotic index was markedly high in the PHx groups; this was prevented by PG treatment. These findings were supported by the ultrastructural results. Our findings indicate that PG supports liver regeneration, hepatocyte proliferation, reduced liver damage, and inflammatory mediators following PHx.

Comparison of ocular surface side effects of topical travoprost and bimatoprost.

PURPOSE: To compare the subjective symptoms, conjunctival hyperemia, tearing response and conjunctival cytological changes secondary to topical administration of bimatoprost and travoprost for 6 months. METHODS: Newly diagnosed primary open-angle glaucoma patients were randomly prescribed bimatoprost (35 cases) or travoprost (42 cases). Two patients in each group were excluded because they did not appear at their appointments regularly. Thus, 33 and 40 patients completed the study in the bimatoprost and travoprost groups, respectively. Redness, itching, foreign-body sensation, pain and discomfort were assessed by a questionnaire, and patients were examined for conjunctival hyperemia. Schirmer's I and break-up time tests were performed, and impression cytology of conjunctiva was evaluated. RESULTS: Subjective symptoms were similar in both groups. The only subjective symptom that changed significantly was redness. The change in conjunctival hyperemia along the study period correlated with the patient-reported redness in both groups, being highest on day 30. Schirmer's test I and break-up time did not change with time and were similar in both groups. The impression cytology grade increased with time in both groups with the only significant difference between groups on day 90 (higher in the bimatoprost group). CONCLUSION: We observed conjunctival hyperemia as the most common side effect of bimatoprost and travoprost. Tear film functions were not affected by these drugs while cytological alterations were.