Preparation, physicochemical, and retinal anti-angiogenic evaluation of poloxamer hydrogel containing dexamethasone/avastin-loaded chitosan-N-acetyl-L-cysteine nanoparticles.

This study was meant to describe a Poloxamer hydrogel combining Chitosan-N-acetyl-L-cysteine (CNAC) nanoparticles to increase loading and sustained intravitreal administration of Avastin macromolecule. To increase the drug's efficacy and reduce the interfacial fluid pressure in a formulation, dexamethasone was used. To do so, CNAC was synthesized. Then, Avastin- loaded CNAC nanoparticles were prepared and optimized. The resulting hydrogel's sol-gel transition time and viscosity were determined using poloxamer and hydroxypropylmethylcellulose (HPMC). In vitro and in vivo investigations of Avastin-loaded CNAC nanoparticles and hydrogel comprising dexamethasone/Avastin-loaded CNAC nanoparticles were determined. In vitro, the drug release profile of optimized hydrogel containing Avastin-loaded CNAC nanoparticles was sustained and controlled over 256 h. The obtained results point to poloxamer/HPMC (18 %/0.5 %) as the best formulations for this hydrogel to develop a sol-gel transition. About 97 % of dexamethasone was released from the hydrogel within 18 h. In vivo results indicated that the optimized formulation compared with free Avastin could improve Diabetic retinopathy (DR). Consequently, we infer that this new drug delivery method may enhance Avastin intravitreal administration, lowering the frequency, danger, and expense of heavy intravitreal injections and resulting in improved treatment of posterior eye segment neovascularization and concomitant vitreoretinal disorders.

Preparation of a biomimetic bi-layer chitosan wound dressing composed of A-PRF/sponge layer and L-arginine/nanofiber.

To better mimic the structure of skin tissue, the use of a multi-layered wound dressing has been proposed. In the present study, a sponge-nanofibrous bi-layer dressing is designed. For this purpose, a chitosan/polyethylene glycol (CsPEG) sponge with advanced platelet-rich fibrin (A-PRF) was prepared as the upper layer of wound dressing, and a Cs/L-arginine electrospun nanofiber layer as the bottom layer. After physical, chemical and mechanical evaluations, the release of platelet-derived growth factor-AB (PDGF-AB), vascular endothelial growth factor (VEGF) and L-arginine were investigated. The antibacterial activity, cell viability and attachment of Bi-layer1.5 dressing (CsPEG/1.5A-PRF sponge coated with Cs/0.5 L-arginine nanofibers) were significantly higher than other dressings. Also, Bi-layer1.5 dressing increased the angiogenic potential and accelerated the wound healing, compared to other samples. Given the promising obtained results, the use of Bi-layer1.5 wound dressing with the ability to release growth factors and L-arginine is highly recommended to treat full-thickness wounds.

Intravenous Administration of Cisplatin with Magnesium Sulfate Supplement May Prevent Kidney Toxicity in Rats: The Role of Gender and Magnesium Sulfate Dose.

BACKGROUND: Cisplatin (CP) is widely used to treat various kinds of malignancies, but to avoid its side effects of nephrotoxicity and hypomagnesemia, magnesium supplementation is a subject of debate. The current study was designed to determine the protective role of intravenous magnesium sulfate (MgSO4) against intravenous administration of CP in male and female rats. METHOD: In this case-control experimental study, 80 Wistar male and female rats in 12 groups of experiments were subjected to receive intravenous administration of CP accompanied with intravenous infusion of different doses (1, 3, and 10 mg/ml solution) of MgSO4 and were compared with the control groups. RESULTS: CP administration increased blood urea nitrogen (BUN), creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW), and they were attenuated by the mid-dose of MgSO4 supplementation in female rats. However, in male rats, the increase of Cr, BUN, KTDS, and KW induced by CP was ameliorated by low, mid-, and high doses of MgSO4 supplements. The levels of these markers were significantly different between male and female rats in the mid-dose of MgSO4-treated group (BUN: P=0.002, Cr: P=0.005, KTDS: P=0.002, and KW: P=0.031). CP reduced clearance of Cr (ClCr) in both male and female rats significantly compared to the control group of saline alone (P male = 0.002 and P female = 0.001), and the mid- and high doses of MgSO4 supplements improved ClCr in female rats. There were also sex differences in ClCr in mid- (P=0.05) and high (P=0.032) doses of MgSO4-treated groups. CP accompanied with the mid-dose of MgSO4 supplement reduced the KTDS (P male = 0.04 and P female = 0.004) and KW (P male = 0.002 and P female = 0.042) in both male and female rats significantly when compared with the CP-alone-treated group, while there were also significant differences between the sexes (KTDS: P=0.002 and KW: P=0.031). CP accompanied with three different doses of MgSO4 supplements did not improve the serum levels of lactate dehydrogenase, urine level of sodium, malondialdehyde, urine flow, and nitrite statistically when compared with the CP-alone-treated group. CONCLUSION: The renal protective effect of MgSO4 could be dose and gender related.

Ulcer-Healing Effect of Hydroalcoholic Extract and Essential Oil of Achillea millefolium L. on Murine Model of Colitis.

Bakground: Ulcerative colitis (UC) is an inflammatory bowel disease that can be treated with many medications but they have various side effects and low cure rate. So, the need for finding novel drugs with better healing characters and less toxicity would be mandatory. Achillea millefolium (A. millefolium, Yarrow) has been traditionally used to treat bleeding, ulcers, wounds, liver, and bile disorders, and recently it has been shown to have anti-ulcer, analgesic, anti-inflammatory, antioxidant, and appetizing effects that make it as a good candidate for UC. Methods: UC was induced with intra-rectal instillation of acetic acid. A. millefolium hydroalcoholic extract (AMHE, 200, 400, and 600 mg/kg/day) and essential oil (AMEO, 62.5, 125, and 250 µl/kg/day) were given to six groups of male Wistar rats for 5 days. Dexamethasone (1 mg/kg/day, intra-peritoneal) and mesalazine (100 mg/kg/day, orally) were used as reference drugs. Colon tissue specimens were separated for assessing macroscopic, pathologic, and biochemical markers. Results: For AMHE, 77.2 mg/g equivalent to gallic acid was obtained for total phenols. Main assessed markers, including ulcer index, total colitis index, colon weight/length ratio, rats' weight gain, and malondialdehyde levels were significantly improved in AMHE (400 and 600 mg/kg/day) and AMEO (125 and 250 µl/kg/day) groups compared to controls. Myeloperoxidase activity was only attenuated in AMHE groups significantly. Conclusions: Both AMHE and AMEO were effective in healing experimental colitis. It seems antioxidant, anti-inflammatory, and anti-ulcer activities of Yarrow are responsible for these beneficial effects. Further studies are warranted to elucidate the exact mechanisms involved.

Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models.

BACKGROUNDS: Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. METHODS: Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. RESULTS: Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly (P < 0.05) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% (P < 0.05). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. CONCLUSION: Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.

Comparative evaluation of BMI-1 proto-oncogene expression in normal tissue, adenoma and papillary carcinoma of human thyroid in pathology samples.

OBJECTIVE: Papillary Thyroid carcinoma accounts for more than 60% of adult thyroid carcinomas. Finding a helpful marker is vital to determine the correct treatment approach. The present study was aimed to evaluate the expression of the B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) gene in papillary carcinoma, adenoma, and adjacent healthy thyroid tissues. Pathology blocks of thyroid tissues at the pathology department of patients who have undergone thyroid surgery between 2015 and 2019 were examined; papillary carcinoma, adenoma, and healthy tissues were selected and sectioned. Total RNA was extracted, and the relative expression level of the BMI-1 gene was examined using the Real-Time qPCR method. RESULTS: In the papillary and adenoma tissues, BMI-1 was overexpressed (1.047-fold and 1.042-fold) in comparison to healthy tissues (p < 0.05 for both comparisons). However, no statistically significant differences were observed between adenoma and papillary carcinoma tissues regarding BMI-1 gene expression. This study demonstrated a new biomarker for thyroid malignancies and found that the mRNA levels of the BMI-1 gene were higher in tumor tissues compared with healthy tissues. Further studies are needed to evaluate the BMI1 gene expression in other thyroid cancers.

Protective Effect of Vitis vinifera (Black Grape) Seed Extract and Oil on Acetic Acid-Induced Colitis in Rats.

BACKGROUND: Vitis vinifera (black grape) is cultivated worldwide and has numerous oral and therapeutic applications. It has proven anti-inflammatory, antioxidant, antimicrobial, and wound healing properties. The aim of this study was to investigate the effect of black grape seed (hydroalcoholic) extract (BGSE) and black grape seed oil (BGSO) on experimental colitis. METHODS: BGSE (50, 100, and 200 mg/kg) and BGSO (2, 4, and 8 mL/kg) were administered orally (p.o.) in groups of six male Wistar rats, 2 h before induction of colitis and continued further for 4 days. Prednisolone (4 mg/kg) and mesalamine (100 mg/kg) were used as reference drugs. Weight/length of colons, macroscopic and histopathologic indices, and biochemical parameters including myeloperoxidase (MPO) and malondialdehyde (MDA) were evaluated. RESULTS: All doses of BGSE and BGSO significantly decreased the colon weight, ulcer index, and total colitis index in comparison with the control group, although greater doses of both fractions had more significant protection. Data of MPO activity revealed that all treated groups with the exception of BGSE (50 mg/kg) and BGSO (2 mL/kg) showed a meaningful decline in comparison with the control group. Concerning the MDA values in colonic tissue, it was demonstrated that BGSE (100, 200 mg/kg) and BGSO (8 mL/kg) caused a significant dip in this oxidative stress parameter. CONCLUSIONS: Oral administration of BGSE and BGSO had an appropriate anti-inflammatory effect and so could be considered as a suitable candidate for treating or preventing ulcerative colitis. Furthermore, detailed studies are warranted to explore the exact mechanism of action and clinical preference of these compounds.

A protocol for irradiation of cell lines cultured in multi-well plates: effect of air inhomogeneity on irradiated cell survival.

Introduction: In multi-well cell culture plates, wells are bordered by air cavities. The air cavity inhomogeneities can reduce the amount of delivered dose. In this study, the effect of these cavities on cell survival was investigated.Materials and methods: A special phantom was designed to house the plates and air cavities were filled by water equivalent materials. Cultured melanoma cells were irradiated using 6MV photon for 200 cGy. MTT and clonogenic assay tests were used to evaluate cell survival.Results: Results of MTT assay showed mean survival percentage for irradiated cells in the first group, i.e. plates with air cavities, was 18.9% higher than the second group with air cavities filled with paraffin. Clonogenic assay results showed a maximum of 37% difference in the mean of number of colonies between the first group and the second group (p value < .05).Conclusions: The presence of air cavities in multi-well cell culture plates reduced radiation cell kill by up to 37%. To ensure the accuracy of delivered dose, it is necessary to replace the air cavities as well as the air surrounding the plates by a water equivalent material.

Classification of chronic myeloid leukemia cell subtypes based on microscopic image analysis.

This paper presents a simple and efficient computer-aided diagnosis method to classify Chronic Myeloid Leukemia (CML) cells based on microscopic image processing. In the proposed method, a novel combination of both typical and new features is introduced for classification of CML cells. Next, an effective decision tree classifier is proposed to classify CML cells into eight groups. The proposed method was evaluated on 1730 CML cell images containing 714 cells of non-cancerous bone marrow aspiration and 1016 cells of cancerous peripheral blood smears. The performance of the proposed classification method was compared to manual labels made by two experts. The average values of accuracy, specificity and sensitivity were 99.0 %, 99.4 % and 98.3 %, respectively for all groups of CML. In addition, Cohen's kappa coefficient demonstrated high conformity, 0.99, between joint diagnostic results of two experts and the obtained results of the proposed approach. According to the obtained results, the suggested method has a high capability to classify effective cells of CML and can be applied as a simple, affordable and reliable computer-aided diagnosis tool to help pathologists to diagnose CML.

Histologic, Histomorphometric, and Osteogenesis Comparative Study of a Novel Fabricated Nanocomposite Membrane Versus Cytoplast Membrane.

PURPOSE: The present study compared the in vivo efficacy of a novel synthesized polycaprolactone (PCL)/polyethylene glycol (PEG)/bioactive glass (BG) nanocomposite membrane versus a cytoplast (Cy) membrane in terms of the average percentage of new bone formation and inflammation levels. MATERIALS AND METHODS: In the present interventional animal study, 12 male New Zealand rabbits were tested. In the parietal bone of the rabbits, 24 defects were prepared (2 defects for each rabbit), which were divided into 3 equal groups (Cy, PCL, and control). Each rabbit's calvarial bone was prepared for the histologic and histomorphometric survey. The amount of regenerated bone (ie, length, area, percentage), necrosis rate, fibrosis (fibrosis plus and percentage), and inflammation in the standard defects of parietal bone in the rabbits were examined and compared after 10 weeks. RESULTS: A significant difference was found between the Cy and PCL groups regarding the mean area and thickness of the bone. We also found a significant difference in the bone length, area, and percentage formed between PCL and control groups. Also, the rate of fibrous tissue formation was significantly different statistically between the PCL and control groups. The results showed the influence of the PCL membrane in generating more bone and less fibrous tissue. In all 3 groups, negligible inflammation and no necrosis was observed. CONCLUSIONS: The results of the present study have shown that combining PCL, PEG, and BGs could be promising for bone regeneration in jaw defects, around dental implants, and in oral and maxillofacial defects.

miR-146a is deregulated in gastric cancer.

BACKGROUND: Gastric cancer is one of the most significant reasons for cancer-related death. miR-146a is one of the dysregulated factors associated with gastric tumorigenesis. However, deregulation of this microRNA (miRNA) has become controversial. Moreover, the inflammation-mediating role of this miRNA implies that miR-146a might be dysregulated by gastric cancer-related pathogens, such as Helicobacter pylori. However, the dysregulation of miR-146a in H. pylori-infected gastric tumors has not been widely studied. OBJECTIVES: We aimed to analyze the expression level of miR-146a in gastric cancer tissues and then to assess any potential association between miR-146a and H. pylori infection and other clinical characteristics. MATERIALS AND METHODS: miR-146a expression level was quantitatively studied by reverse transcription quantitative polymerase chain reaction, in 144 fresh tissues including 44 normal and 100 gastric cancer samples. RESULTS: A dramatic overexpression of miR-146a was observed in primary gastric tumors. miR-146a showed lower expression in progressed tumors with greater stages and lymph node metastasis. CONCLUSION: miR-146a is highly expressed in primary gastric tumor independent of H. pylori infection. It is highly expressed in the lower stages and lymph node-negative tumors. It might suggest the importance of upregulation and downregulation of this miRNA in the initiating/promoting and progressive steps of gastric tumorigenesis, respectively.

Nanocrystalline cellulose-hyaluronic acid composite enriched with GM-CSF loaded chitosan nanoparticles for enhanced wound healing.

In recent years, applications of biopolymers such as hyaluronic acid (HA) for wound dressing have attracted more attention. However, the poor mechanical properties of HA-based wound dressings limit their clinical applications. Incorporation of reinforcing agents such as nanocrystalline cellulose (CNC) in HA-based wound dressings can improve their mechanical properties. In addition, controlled delivery of growth factors to the wound site using nanoparticles can significantly improve the healing process. In this study, we focus on development and characterization of a novel CNC reinforced HA-based composite containing chitosan nanoparticles loaded with GM-CSF (CNC-HA/GM-CSF-Chi-NPs composite) as an effective wound dressing. CNC-HA/GM-CSF-Chi-NPs composite showed some physicochemical characteristics such as appropriate mechanical properties, high swelling capacity (swelling ratio: 2622.1% ± 35.2%) and controlled release of GM-CSF up to 48 h which make it an excellent candidate for wound dressing. In vivo investigation showed that, after 13 d, the wounds covered with CNC-HA/GM-CSF-Chi-NPs composite could reach to nearly full wound closure and complete re-epithelialization compared to the normal saline treated wounds which exhibited nearly 70% of wound size reduction. Furthermore, the CNC-HA/GM-CSF-Chi-NPs composite treated wounds exhibited significantly lower inflammatory reaction, enhanced re-epithelialization and improved granulation tissue formation compared with CNC-HA/Chi-NPs composite treated wound; it might be due to positive effects of GM-CSF on the wound healing process. Our results suggest that CNC-HA/GM-CSF-Chi-NPs composite can be potentially applied in clinical practice for wound treatment.

Effect of Long-term Administration of Oral Magnesium Sulfate and Insulin to Reduce Streptozotocin-Induced Hyperglycemia in Rats: the Role of Akt2 and IRS1 Gene Expressions.

The effects of long-term oral administration of magnesium sulfate and insulin on hyperglycemia were investigated using Akt2 and IRS1 gene expression methods in streptozotocin-induced diabetic rats. Fifty rats were randomly divided into five experimental groups: 1, non-diabetic control (NDC); 2, Mg2+-treated non-diabetic control (Mg-NDC); 3, chronic diabetic (CD); 4, Mg2+-treated chronic diabetic (Mg-CD); and 5, insulin-treated chronic diabetic (Ins-CD). Streptozotocin was used to induce diabetes. The Mg-CD and Mg-NDC groups received 10 g/l of MgSO4 added to drinking water. The Ins-CD group received 2.5 U/kg of insulin twice a day. Blood glucose level and body weight were measured every week. The intraperitoneal glucose tolerance test (IPGTT) was performed after 16 weeks. MgSO4 administration improved the blood glucose level and IPGTT. It also increased Akt2 and IRS1 genes as well as protein expression. Insulin lowered the blood glucose level and increased IRS1 gene and protein expression, but did not affect Akt2 gene and protein expression. Glucose reduction after Mg therapy may be mediated, at least partially, via IRS1 and Akt2 genes and protein stimulation. In insulin-treated rats, insulin resistance was not significant due to the absence of Akt2 gene expression.

Effect of freeze drying on stability, thermo-responsive characteristics, and in vivo wound healing of erythropoietin-loaded trimethyl chitosan/glycerophosphate hydrogel.

Erythropoietin (EPO) was successfully incorporated into a bioadhesive thermosensitive hydrogel based on trimethyl chitosan (TMC)/ß-glycerophosphate (GP) for prevention and treatment of oral mucositis in cancerous patients. The aim of the present study was to evaluate the effect of freeze drying on thermo-responsive property of the hydrogel and structural stability of the loaded protein. The freeze-dried EPO-loaded hydrogel were characterized using various methods. Gelation property by rheological analysis, EPO aggregation in formulations by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), protein secondary structure by far ultraviolet-circular dichroism (CD), and the antigenic activity of EPO with ELISA techniques. The healing effects of the freeze-dried formulation was also investigated in Sprague-Dawley rats with chemotherapy-induced mucositis and compared with freshly prepared mixture. Finally, the retention time of the gel in the oral cavity was assessed in healthy volunteers. SDS-PAGE, CD, and ELISA confirmed the stability of conformational structure of loaded and released EPO. Severity of mucositis was markedly reduced in animals treated with freeze-dried EPO hydrogel; whereas the group received normal saline did not show any significant healing. EPO salvia level was decreased rapidly following EPO solution compared to the gel application. Approximately, 40% of EPO was maintained on the buccal areas in patients receiving the hydrogel system after 30 min. Therefore, the TMC/GP could preserve EPO stability after freeze drying and has the potential in the treatment of oral mucositis and other oral or subcutaneous wounds.

Computer-aided diagnosis software for vulvovaginal candidiasis detection from Pap smear images.

Vulvovaginal candidiasis (VVC) is a common gynecologic infection and it occurs when there is overgrowth of the yeast called Candida. VVC diagnosis is usually done by observing a Pap smear sample under a microscope and searching for the conidium and mycelium components of Candida. This manual method is time consuming, subjective and tedious. Any diagnosis tools that detect VVC, semi- or full-automatically, can be very helpful to pathologists. This article presents a computer aided diagnosis (CAD) software to improve human diagnosis of VVC from Pap smear samples. The proposed software is designed based on phenotypic and morphology features of the Candida in Pap smear sample images. This software provide a user-friendly interface which consists of a set of image processing tools and analytical results that helps to detect Candida and determine severity of illness. The software was evaluated on 200 Pap smear sample images and obtained specificity of 91.04% and sensitivity of 92.48% to detect VVC. As a result, the use of the proposed software reduces diagnostic time and can be employed as a second objective opinion for pathologists.

The Best Texture Features for Leukocytes Recognition.

BACKGROUND: Differential counting of white blood cells (WBCs or leukocytes) is a common task to diagnose many diseases such as leukemia, and infections. An accurate process for recognizing leukocytes is to evaluate a blood smear under a microscope by an expert. Since, this procedure is manual, time-consuming and tedious, making the procedure automatic would overcome these problems. In an automated CAD (Computer-Aided-Design) system for this purpose, a crucial module is leukocytes recognition. In this paper, we are looking for the best features in order to recognize five types of leukocytes (Monocyte, Lymphocyte, Neutrophil, Eosinophil and Basophil) from microscopic images of blood smear in an automated cell counting system. METHODS: In this work, we focus on the texture features and seven categories: GLCM features, Haralick features, Spectral texture features, Wavelet-based features, Gabor-based features, CoALBP and RICLBP are analyzed to find the best features for leukocytes detection. The best features of each category are selected using stepwise regression and finally three well-known classifiers called K-NN, LDA and NB are utilized for classification. RESULTS: The proposed system is tested on a self-provided dataset composed of 200 cell images. In our experiments, to evaluate the process, the accuracy of each leukocyte type and the mean accuracy are computed. RICLBP features achieved the best mean accuracy (85.53%) for LDA classifier. CONCLUSIONS: In our experiments, although the maximum mean accuracy (85.53%) went with RICLBP features, but the accuracies of all five leukocyte types weren't maximized for RICLBP features. This result directs us to design and develop a system based on multiple features and multiple classifiers to maximize the accuracies even for each individual cell type in our future work.

Evaluation of the central and peripheral effects of doxepin on carrageenan-induced inflammatory paw edema in rat.

The anti-inflammatory effects of anti-depressants have been demonstrated recently. Doxepin, a tricyclic antidepressant drug (TCA), has some special properties in comparison with the other members of its family. It has some H1, H2, alpha-1 adrenergic and muscarinic receptor blocking effects. It revealed also anti-nociceptive and relatively potent sedative effects. This study was aimed to evaluate its possible anti-inflammatory effect in a well-established animal model. Male Wistar rats weighing 200-250 g were used in carrageenan-induced inflammatory paw edema model. The test and control drugs were injected by intraperitoneal (i.p.) and intracerebral (i.c.v.) routes. The anti-inflammatory activity of doxepin (15, 30 and 60 mg/kg, i.p. and 50 and 100 µg/rat, i.c.v.) and the reference drug, dexamethasone (2 mg/kg, i.p.) were evaluated by determination and comparison of some involved biological markers including the paw volume, cytokine levels (interleukin 6 (IL-6), IL-1ß, tumor necrosis factor α (TNFα)), myeloperoxidase (MPO) activity and histopathological parameters. All i.p. doses of doxepin showed significant anti-inflammatory effect. It also significantly reduced MPO activity and cytokine levels and improved histopathologic parameters of carrageenan-injected paw tissues. I.c.v. administration of the drug did not show any significant reduction of carrageenan-induced paw edema. Although the exact mechanism of the anti-inflammatory effect of doxepin is not clear, it seems that reduced leukocyte migration and pro-inflammatory cytokines play important role in its anti-inflammatory effect. Also central sites are not involved in the anti-inflammatory effect of the drug.

The Role of Gamma Amino Butyric Acid in Cisplatin-induced Nephrotoxicity in Streptozotocin-induced Diabetic Rats.

BACKGROUND: Diabetes mellitus can change the risk of developing cancer. Cisplatin (CP) is a common antineoplastic drug. The major side effect of CP is nephrotoxicity. Gamma amino butyric acid (GABA) is an antioxidant agent that may have a protective role against CP-induced nephrotoxicity. The aim of the present study was to investigate the role of GABA in CP-induced nephrotoxicity in hyperglycemic male and female rats. MATERIALS AND METHODS: Sixty male and female Wistar diabetic rats were used in ten experimental groups. GABA alone groups received GABA (50 µmol/kg/d i.p.) for 12 days. CP alone groups received CP (2.5 mg/kg/d i.p.) for 6 days. Other groups received GABA in the form of therapy (T) + CP, prophylaxis (P) + CP, and prophylaxis-treatment (PT) + CP. Finally, blood samples were obtained, and animals were killed for kidney tissue investigation. RESULTS: In female rats, the serum levels of creatinine (Cr) did not change by GABA rather than CP and also there were no significant changes in blood urea nitrogen to creatinine ratio (BUN/Cr). In male rats, plasma Cr level increased by GABA (P) and (T). Body weight loss was significantly different among groups (P < 0.05). BUN/Cr ratio significantly increased in CP and GABA (PT) + CP groups. In two genders, plasma Cr level significantly decreased in CP groups (P < 0.05). The kidney levels of malondialdehyde enhanced significantly in CP groups. CONCLUSION: Hyperglycemia has protective effect against CP-induced nephrotoxicity. GABA did not change this effect in female, but in male in the form of PT, GABA maintained it.

Age and Gender Related Renal Side Effects of Cisplatin in Animal Model

Backgrounds: Cisplatin (CDDP) is a choice of anti-cancer drug for cancer chemotherapy with serious side effects such as nephrotoxicity. It seems that age is an important factor influencing the side effects of CDDP. This study was designed to determine the role of age and gender simultaneously in CDDP induced renal toxicity. Methods: 40 Wistar male and female rats were assigned as 6 groups in 3 different age categories (10, 16, and 20 weeks old). The single dose of CDDP (7.5 mg/kg, ip) was administrated, and a week later measurements were performed. Results: Body weight changes in male (not in female) animals aged 16 and 20 weeks were more than 10 weeks old animals (P<0.05). In male rats, the serum levels of creatinine (Cr) and blood urea nitrogen (BUN), and Cr-clearance in aged 10 weeks, normalized kidney weight (KW) in aged 20 weeks, and serum nitrite, aspartate aminotransferase (AST) and malondialdehyde (MDA) levels and kidney tissue damage score (KTDS) in rats aged 16 weeks were significantly altered (P<0.05). Gender difference in serum level of Cr, BUN and nitrite, and Cr-clearance were observed in animals aged10 weeks (P<0.05). Conclusion: The side effects of CDDP are gender depended, and may be different at various ages.

Segmentation of White Blood Cells From Microscopic Images Using a Novel Combination of K-Means Clustering and Modified Watershed Algorithm.

Recognition of white blood cells (WBCs) is the first step to diagnose some particular diseases such as acquired immune deficiency syndrome, leukemia, and other blood-related diseases that are usually done by pathologists using an optical microscope. This process is time-consuming, extremely tedious, and expensive and needs experienced experts in this field. Thus, a computer-aided diagnosis system that assists pathologists in the diagnostic process can be so effective. Segmentation of WBCs is usually a first step in developing a computer-aided diagnosis system. The main purpose of this paper is to segment WBCs from microscopic images. For this purpose, we present a novel combination of thresholding, k-means clustering, and modified watershed algorithms in three stages including (1) segmentation of WBCs from a microscopic image, (2) extraction of nuclei from cell's image, and (3) separation of overlapping cells and nuclei. The evaluation results of the proposed method show that similarity measures, precision, and sensitivity respectively were 92.07, 96.07, and 94.30% for nucleus segmentation and 92.93, 97.41, and 93.78% for cell segmentation. In addition, statistical analysis presents high similarity between manual segmentation and the results obtained by the proposed method.