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1.
Mol Pharm ; 20(10): 5090-5107, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37624646

RESUMO

Pharmaceutical cocrystals ( Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry; Food and Drug Administration, 2018) are crystalline solids produced through supramolecular chemistry to modulate the physicochemical properties of active pharmaceutical ingredients (APIs). Despite their extensive development in interdisciplinary sciences, this is a pioneering study on the efficacy of pharmaceutical cocrystals in wound healing and scar reducing. Curcumin-pyrogallol cocrystal (CUR-PYR) was accordingly cherry-picked since its superior physicochemical properties adequately compensate for limitative drawbacks of curcumin (CUR). CUR-PYR has been synthesized by a liquid-assisted grinding (LAG) method and characterized via FT-IR, DSC, and PXRD analyses. In vitro antibacterial study indicated that CUR-PYR cocrystal, CUR+PYR physical mixture (PM), and PYR are more effective against both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria in comparison with CUR. In vitro results also demonstrated that the viability of HDF and NIH-3T3 cells treated with CUR-PYR were improved more than those received CUR which is attributed to the effect of PYR in the form of cocrystal. The wound healing process has been monitored through a 15 day in vivo experiment on 75 male rats stratified into six groups: five groups treated by CUR-PYR+Vaseline (CUR-PYR.ung), CUR+PYR+Vaseline (CUR+PYR.ung), CUR+Vaseline (CUR.ung), PYR+Vaseline (PYR.ung), and Vaseline (VAS) ointments and a negative control group of 0.9% sodium chloride solution (NS). It was revealed that the wounds under CUR-PYR.ung treatment closed by day 12 postsurgery, while the wounds in other groups failed to reach the complete closure end point until the end of the experiment. Surprisingly, a diminutive scar (3.89 ± 0.97% of initial wound size) was observed in the CUR-PYR.ung treated wounds by day 15 after injury, followed by corresponding values for PYR.ung (12.08 ± 2.75%), CUR+PYR.ung (13.89 ± 5.02%), CUR.ung (16.24 ± 6.39%), VAS (18.97 ± 6.89%), and NS (20.33 ± 5.77%). Besides, investigating histopathological parameters including inflammation, granulation tissue, re-epithelialization, and collagen deposition signified outstandingly higher ability of CUR-PYR cocrystal in wound healing than either of its two constituents separately or their simple PM. It was concluded that desired solubility of the prepared cocrystal was essentially responsible for accelerating wound closure and promoting tissue regeneration which yielded minimal scarring. This prototype research suggests a promising application of pharmaceutical cocrystals for the purpose of wound healing.


Assuntos
Antioxidantes , Cicatriz , Curcumina , Pirogalol , Cicatrização , Animais , Masculino , Camundongos , Ratos , Cicatriz/tratamento farmacológico , Cicatriz/prevenção & controle , Curcumina/administração & dosagem , Curcumina/química , Curcumina/farmacologia , Curcumina/uso terapêutico , Preparações Farmacêuticas , Espectroscopia de Infravermelho com Transformada de Fourier , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia , Cristalização , Pirogalol/administração & dosagem , Pirogalol/química , Pirogalol/farmacologia , Pirogalol/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Vaselina/administração & dosagem
2.
Iran Endod J ; 18(2): 91-95, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152857

RESUMO

Introduction: Diagnosis of dental pulp status on the basis of clinical signs in many cases helps clinicians to better resolve patient problems. Various studies have shown no correlation between clinical and histologic findings. The aim of the present study was to evaluate the associations between clinical findings and histological features in extracted decayed teeth with acute pulpitis. Materials and Methods: One hundred permanent cavitated human teeth with mature apices and pulpitis, which were extracted for reasons not related to the present study, were evaluated. Demographic, clinical, and radiographic data were collected using pre-designed questionnaires. After tooth extraction, 5 micron-thick slices were prepared for microscopic assessment. General pathologist evaluated reactions to stimuli in all areas of the pulp tissue under a light microscope. When present, inflammation was classified according to the type and spread of cell detected and other histological findings, such as abscess formation, pulp stones, and pulpal fibrosis, were also recorded. Results: We found significant associations between pain characteristics, such as pain type and duration, and histological status. Acute inflammation, severe chronic inflammation, and liquefactive necrosis increased with pain severity. Various histological sections showed the absence of pulpal inflammation. Conclusions: We found a good agreement of patients' pain histories and pain characteristics with histological pulp status. Thus, the use of specified CHARTs and SCALEs that help patients provide the most accurate responses to questions about pain would aid the diagnosis of pulp status. In cases with an accurate pulpal diagnosis, the clinicians can manage pulpal protection when it is possible.

3.
Int J Biol Macromol ; 240: 124427, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37060977

RESUMO

One of the goals of wound repairing is to mimic the function and architecture of the native extracellular matrix (ECM). To this end, for the first time, we used pluronic F127 and mesoporous rod-like hydroxyapatite nanoparticles (mr-HAP NPs) simultaneously to prepare a novel low-diameter electrospun ECM-mimicking wound dressing based on a mixture of chitosan and polyethylene oxide. F127 is used as a surface tension regulator of the polymer solution. In addition, F127 has the special ability to reduce the size of nanofibers. mr-HAP NPs are used as cell proliferation accelerators which also improve the mechanical properties and water uptake capacity of the as-prepared dressing. The average size of nanofibers in the presence of F127 was about 110 nm which was more than 2.5 times lower than nanofibers prepared without F127. The water uptake capacity was evaluated to investigate the wound exudate absorption capacity of the wound dressing. It was observed that the incorporation of mr-HAP NPs into wound dressing structure increases the water uptake capacity by more than 2.5 times. Alongside the evaluation of cytocompatibility through in vitro cell viability assay, the wound healing efficacy was also determined in full-thickness skin wounds in a rat model for 15 days. The cytocompatible wound dressing showed significantly higher wound closure efficacy than the control group so the wounds healed entirely on the last day of the treatment period. As well, the pathology analysis proved better granulation tissue development and greater re-epithelialization. These findings are by virtue of the improved mechanical properties, accelerated cell migration and proliferation, proper environment for oxygen exchange, and enhanced exudate uptake of the wound dressing. These all are due to the presence of F127 and mr-HAP.


Assuntos
Quitosana , Nanofibras , Nanopartículas , Ratos , Animais , Quitosana/química , Poloxâmero , Durapatita , Nanofibras/química , Cicatrização , Água , Nanopartículas/química , Antibacterianos/química
4.
Iran J Otorhinolaryngol ; 35(126): 39-47, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36721411

RESUMO

Introduction: Cervical adenopathy can be involved in various pathological processes. This study aimed to evaluate the ultrasound classification of cervical adenopathy (A-RADS) to choose the appropriate approach. Materials and Methods: This cross-sectional study was conducted among 294 patients with cervical adenopathy at Mashhad University of Medical Sciences during 2020-2021. The data of the long axis diameter, short axis diameter, shape, border, vascular pattern, presence of calcification and changes in cyst/necrosis, cortical echogenicity, hilum visibility, and location of involved lymph nodes were extracted. Lymph nodes was classified into four normal, reactive, suspicious & lymphoid disorders, and metastatic groups, based on ultrasound appearance (Adenopathy-reporting and data system). Diagnostic methods included follow-up, core needle biopsy (CNB), and fine needle aspiration (FNA), and surgical results. After determining the final diagnosis, demographic, sonographic, and pathological data were analyzed at a significance level of p<0.05. Results: Of 294 patients, 185 were benign, and 109 were malignant. There were no significant differences in the location, long axis diameter, shape, cystic or necrotic changes, calcification, and margins of the lymph nodes between the benign and malignant groups. The enlarged short axis diameter, invisible hilum with isoechoic cortex, and non-hilar vascularity were significantly higher in the malignant group (p<0.001). The malignancy rate was 8.7% in reactive cases, 48.5% in lymphoid disorders, and 90% in metastatic nodes. Conclusion: The results of this study shows that cervical lymph nodes can be classified based on short axis diameter, cortex and hilum echo-texture and vascular pattern into normal, reactive, suspicious & lymphoid disorders, and metastatic, which have a high concordance with pathologic results.

5.
Clin Case Rep ; 10(4): e05719, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35498348

RESUMO

A 26-year-old man presented to the emergency department due to headache, nausea, and vomiting. He had a right subclavicular slow-growing mass. Histopathological evaluation showed alveolar soft part sarcoma. The patient was found to have multiple cerebral and pulmonary metastases. So far, he has got three cycles of brain radiotherapy.

6.
Eur J Pharm Sci ; 168: 106072, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34774715

RESUMO

Formulation design for colon-specific delivery of 5-aminosalicylic acid (5-ASA) could bring some therapeutic benefits in the treatment of ulcerative colitis (UC). In the current study, a 32 full factorial design was used to predict optimum coating composed of two enteric (poly methacrylic acid, methyl methacrylates 1:2 and 1:1) and time-dependent (poly ethyl acrylate, methyl methacrylate, trimethylammonio ethyl methacrylate chloride 1:2:0.1) polymethacrylates for colon-specific delivery of 5-ASA pellets. A unique coating composition and coating level predicted by the model was applied onto either inulin-free 5-ASA pellets or inulin-bearing 5-ASA pellets and the coated pellets were examined by dissolution test in-vitro. The coated pellets were also tested in a rat model of UC and compared with the a commercially available colonic delivery system of 5-ASA. The ratio of the two enteric polymethacrylates and time-dependet polymethacrylate of 16:64:20 w/w at a coating level of 15% was discovered as the optimum coating for delivery of 5-ASA pellets to the colon. In general, the coated pellets offered a better therapeutic outcome compared to commercially available colonic delivery system of 5-ASA and uncoated pellets in terms of colitis activity index and the colon's tissue enzymes of MDA and GSH. It seems that the coating composed of enteric and pH-dependent polymethacrylates could tune up the rate of drug release from 5-ASA-coated pellets and trigger drug release based on pH and time.


Assuntos
Colite Ulcerativa , Mesalamina , Animais , Colite Ulcerativa/tratamento farmacológico , Colo , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Mesalamina/uso terapêutico , Ácidos Polimetacrílicos , Ratos , Solubilidade
7.
J Cardiol Cases ; 23(5): 198-201, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33995695

RESUMO

Lymphoma is one of the most common tumors with the risk of cardiac metastasis. The pattern of cardiac involvement is usually as focal masses. As early diagnosis of lymphoma plays a crucial role in its response to treatment and patient survival longevity, we report a rare case of cardiac lymphoma with diffuse cardiac involvement and acquired pulmonary stenosis. The patient was referred to our center for further evaluation because of dyspnea and systolic ejection murmur. In pericardial biopsy, T cell lymphoblastic lymphoma was reported. After a full course of chemotherapy and one-year follow up, symptoms had improved and echocardiography was normal except for small pericardial effusion. .

8.
Int J Pharm ; 597: 120347, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33545282

RESUMO

A tunable release of 5-aminosalicylic acid (5-ASA) could bring therapeutic benefits in the treatment of inflammatory bowel disease (IBD). A 32 factorial design was used to achieve a tuned delivery of 5-ASA pellets in the small and large intestine using a coating composed of inulin/Eudragit RS (RS). The ratio of inulin/RS and coating level were independent variables while the dependent variables were the percent of drug release at pH 1.2 in 2 h and total release of drug in 10 h at pH 6.8. 5-ASA release from pellets was examined at different pH levels and the therapeutic efficacy of the optimum pellets was compared to 5-ASA pellets of Pentasa in rats with ulcerative colitis. The inulin/RS of 18/82 at a coating level of 16% was found to be the optimum for delivery of the drug to the small and large intestine. The coated pellets offered a superior therapeutic outcome compared to uncoated pellets and Pentasa in terms of colitis activity index (CAI), and the colon's tissue enzymes of GSH and MDA. The optimum coating composed of inulin and RS could offer a tuned sustained release of 5-ASA throughout the small and large intestine with the sensitivity of drug release to microbial degradation.


Assuntos
Colite Ulcerativa , Mesalamina , Resinas Acrílicas , Animais , Colite Ulcerativa/tratamento farmacológico , Preparações de Ação Retardada , Inulina , Modelos Animais , Ratos
9.
Iran J Pathol ; 15(4): 326-333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944046

RESUMO

BACKGROUND & OBJECTIVE: Matrix metalloproteinases-9 (MMP-9) is one of the most important enzymes to breakdown extracellular matrix which plays a major role in tumor invasion and metastasis. This study aimed to determine tumor MMP-9 expression in non-small-cell lung carcinoma (NSCLC) and whether it is associated with histopathologic factors and has prognostic value to affect overall survival (OS). METHODS: The specimens of 92 patients with NSCLC diagnosis were included. Tumor sections were stained by immunohistochemistry method. Using scores for the percentage of cells positively stained and the intensity of staining, MMP-9 expression total score was classified as low-score (scores of 0 to 2), moderate-score (scores of 3 to 5), or high-score (scores of 6 or 7). OS was defined as the time interval since the diagnosis of NSCLC to the status at the last follow-up (dead or alive). The follow up period was up to 70 months. RESULTS: About 74% of undifferentiated specimens (grade III tumors) showed high scores for MMP-9 expression which was significantly higher than moderately differentiated tumors (25% had high scores for MMP-9 expression) and well differentiated ones which did not have high scores (P<0.001). A total of 74 patients (80.4%) died during the follow-up period. Of this, 36% had high scores for MMP-9 expression. In contrast, none of the patients who were alive at the last follow-up had high scores for MMP-9 expression (P<0.001). Median OS was significantly lower in high score group (6 months) compared to moderate score (9 months) and high score group (15 months) (P<0.001). CONCLUSION: MMP-9 expression may serve as a significant prognostic factor for mortality and overall survival in NSCLC. Undifferentiated tumors significantly express higher MMP-9 immunohistochemically.

10.
Iran J Basic Med Sci ; 23(7): 853-857, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32774805

RESUMO

OBJECTIVES: To validate certain markers for cancer stem cell populations and their clinical importance in Wilms tumor (WT). MATERIALS AND METHODS: Immunohistochemical study for CD133 and CD56/NCAM was performed on forty-six cases of WT that were diagnosed between 1999 and 2015, and the association of these markers with survival and prognostic factors was analyzed. RESULTS: Thirty-four (73.9%) of WTs were positive for CD133 and thirty-nine (84.8%) were positive for CD56/NCAM. A significant positive correlation between CD133 and CD56/NCAM expression and the National Wilms Tumor Stage (NWTS) and death was found. Moreover, overall survival time was significantly correlated with CD133 and CD56/NCAM H-score, NWTS stage, and death. CONCLUSION: It seems that CD133 and CD56/NCAM expressions can be used as strong prognostic parameters for the survival of patients with WT and can be used to predict WT patients' stage. Moreover, their targeted therapies can abolish cancer stem cells in children with recurrent tumors.

11.
Arch Bone Jt Surg ; 8(3): 454-456, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32766407

RESUMO

Primary synovial sarcoma of mediastinum is very rare among soft tissue sarcomas. Only a few cases have been reported in the literatures. The best treatment is still unclear, but, surgical resection is the main therapy. In this article we report a case of a 20*20 cm (2000gr) primary giant mediastinal synovial sarcoma in a 42 year-old man. We performed radical excision of the tumor and the metastasis.

12.
Eur J Pharmacol ; 883: 173310, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32619674

RESUMO

Hemorrhagic cystitis is one of the most important complications of cyclophosphamide, a drug widely used in cancer chemotherapy and bone marrow transplantation. 5-HT3 antagonists are anti-emetic agents and have been shown to have notable anti-inflammatory and antioxidant properties. This study was designed to investigate the possible protective effects of tropisetron against cyclophosphamide-induced hemorrhagic cystitis in rats. Hemorrhagic cystitis was induced in female rats by cyclophosphamide (270 mg/kg). Tropisetron (2.5, 5 and 7.5 mg/kg), granisetron (2.5 and 5 mg/kg), and ondansetron (5 mg/kg) were injected 15 min before, 4 and 8 h after cyclophosphamide. To evaluate the role of alpha7 nicotinic acetylcholine receptor (α7nAChR), its antagonist, methyllycaconitine (5 mg/kg) was administered 30 min before tropisetron. After 24 h, animals were killed under anesthesia. Macroscopic and histological changes were evaluated. Malondialdehyde (MDA), glutathione (GSH) and Evans blue were measured spectrophotometrically. Furthermore, the protein levels of p38 mitogen-activated protein kinases (P38 MAPK), p-P38, signal transducer and activator of transcription 3 (STAT3), p-STAT3 and Poly (ADP-ribose) polymerase (PARP) were determined using Western blot. Cyclophosphamide administration significantly induced histopathological damages and increased MDA, p-p38/p38, p-STAT3/STAT3, and PARP levels compared with the saline group. Tropisetron treatment diminished histopathological injuries as well as MDA level, and STAT3 activity compared to cyclophosphamide treated rats. Co-administration of methyllycaconitine with tropisetron, partially or completely reversed the protective effects of tropisetron. Our results showed that prophylactic administration of tropisetron markedly ameliorated the cyclophosphamide-induced bladder hemorrhage and inflammation in rats. These effects of tropisetron were α7nAChR dependent.


Assuntos
Cistite/prevenção & controle , Hemorragia/prevenção & controle , Agonistas Nicotínicos/farmacologia , Tropizetrona/farmacologia , Bexiga Urinária/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Animais , Anti-Inflamatórios/farmacologia , Ciclofosfamida , Cistite/induzido quimicamente , Cistite/metabolismo , Cistite/patologia , Modelos Animais de Doenças , Feminino , Granisetron/farmacologia , Hemorragia/induzido quimicamente , Hemorragia/metabolismo , Hemorragia/patologia , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Ondansetron/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos Wistar , Fator de Transcrição STAT3/metabolismo , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Transdução de Sinais , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Indian J Dermatol ; 65(1): 29-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32029936

RESUMO

INTRODUCTION: Psoriasis is an autoimmune disease. The important role of oxidative stress in the pathogenesis of psoriasis had been investigated in different studies. Thioredoxin reductase (TrxR) is a selenocysteine-containing enzyme which is involved in the protection of cells against oxidative stress. Here, we investigated the TrxR activity in skin lesions of psoriatic patients and the possible correlation between this activity and the severity of the disease that was scored based on the Psoriasis Area and Severity Index (PASI). MATERIALS AND METHODS: TrxR activity was determined using TrxR colorimetric method based on the reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) to 5-thio-2-nitrobenzoic acid by TrxR using nicotinamide adenine dinucleotide phosphate in 20 psoriatic patients (11 men and 9 women) aged 38.9 ± 12.6 years. For evaluating the disease severity, PASI score system (mild [PASI <10], moderate [PASI 10-20], or severe [PASI >20]) was utilized that was based on three factors including thickness, erythema, and scaling of lesions. RESULTS: Our results revealed that the TrxR activity between different groups of psoriatic patients (according to the PASI score) was statistically significant and it was higher in psoriatic patients with mild disease (correlation coefficient = -0.85). CONCLUSION: These results further strengthen the association between psoriasis and oxidative stress. The increased level of TrxR could be due to the protective effect of this enzyme against the inflammatory process and oxidative stress. Moreover, TrxR could be used as a novel marker for evaluating psoriasis severity.

14.
Iran J Pathol ; 15(1): 30-33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32095147

RESUMO

BACKGROUND & OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a chronic and uniformly fatal interstitial lung disease with incompletely understood pathogenesis. Several studies have given the evidence for and against viral cofactors in the pathogenesis of Idiopathic pulmonary fibrosis. In this study Epstein-Bar Virus (EBV) and Human Herpesvirus 8 (HHV-8) have been studied for a possible role in the pathogenesis of IPF. METHODS: Polymerase chain reaction (PCR) was employed for the detection of EBV and HHV-8 in 58 formalin-fixed paraffin-embedded lung tissue specimens (29 controls and 29 IPF specimens). RESULTS: EBV DNA was present in the lung tissue of 6 out of 29 (20.7%) IPF specimens compared with 1 out of 29 (3.4%) controls (P=0.102). The HHV-8 gene was identified in 3 out of 29 (10.3%) cases of IPF specimens. The control group showed no evidence of HHV-8 gene (P=0.227). CONCLUSION: Although multiple studies are strongly suggestive of a role for EBV and HHV-8 in the development of IPF, there was no statistically significant difference in the prevalence of EBV and HHV-8 DNA in the IPF specimens and controls in this study.

15.
Drug Chem Toxicol ; 43(6): 609-615, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31264488

RESUMO

Despite the widespread use of Rheum turkestanicum in herbal medicine, no study has yet examined its in vivo toxicity. The aim of this study is to evaluate the acute and sub-acute toxicity of hydroalcoholic extract of R. turkestanicum root. In acute toxicity experiment, female and male mice (n = 5/group/sex) were orally administrated with the extract at single doses of 300, 2000 and 3000 mg/kg and observed for 14 days. In the sub-acute study, the extract was orally administered daily at doses of 100 and 400 mg/kg to male rats (n = 8) for 4 weeks. During the acute toxicity test, there were no deaths or any signs of toxicity observed after administration of the R. turkestanicum extract at 300 mg/kg, which was the no-observed-adverse-effect level (NOAEL). The extract at a dose of 3000 mg/kg led to the death of one female and one male mouse (LD50 > 3000 mg/kg). In sub-acute toxicity experiment, the extract induced no mortality or significant changes in body weight, general behaviors, hematological parameters, serum biochemical factors (related to the kidney and liver function), and histopathology of the heart, liver, kidney, and brain up to the highest dose tested of 400 mg/kg (NOAEL). High-performance liquid chromatography-mass spectrometry revealed the presence of phenolic compounds, flavonoids, alkanes, and anthraquinones in the extract. In conclusion, short-term use of R. turkestanicum root does not appear to produce significant toxicity up to a dose of 400 mg/kg.


Assuntos
Extratos Vegetais/toxicidade , Raízes de Plantas/toxicidade , Rheum/toxicidade , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Administração Oral , Animais , Biomarcadores/sangue , Feminino , Dose Letal Mediana , Masculino , Camundongos , Nível de Efeito Adverso não Observado , Extratos Vegetais/administração & dosagem , Ratos Wistar , Medição de Risco , Fatores de Tempo
16.
J Pharmacopuncture ; 22(3): 147-153, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31673444

RESUMO

OBJECTIVES: Many studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients. METHODS: We used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken. RESULTS: Our results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity. CONCLUSION: In conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.

17.
Iran J Pathol ; 14(4): 299-304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754359

RESUMO

BACKGROUND & OBJECTIVE: In Triple-Negative Breast Cancers (TNBCs), estrogen receptor (ER), progesterone receptor (PR) and HER2/neu genes are not expressed. Fibroblastic Growth Factor Receptor-1 (FGFR1) gene product is a protein that acts as a receptor of thyrosin kinase. It plays a role in the proliferation, differentiation, and migration of malignant cells. The objective was to evaluate the possible relation between FGFR1 over-expression and amplification in TNBCs and other clinicopathological variables. METHODS: In this cross sectional study, purposive sampling was used to collect eighty-four TNBC specimens from mastectomy specimens collected between 2013 and 2017. Tissue microarrays were evaluated for FGFR1 over-expression and amplification respectively by immunohistochemistry (IHC) staining and real time Polymerase Chain Reaction (PCR). The needed clinical and paraclinical information were obtained from patients' files. To analyze the correlation among prognostic factors, we used a wide range of different statistic methods, namely Chi-square test, independent t-test, Fisher's exact test, and ANOVA. RESULTS: FGFR1 over-expression was found in 15 of the 84 samples (17.9%). FGFR1 gene amplification was observed in 33.3% (28 of 84) of the samples. We found no association between FGFR1 and clinicopathological parameters, including tumor grade, stage, and patient survival (P>0.005). CONCLUSION: FGFR1 over-expression and amplification may not be related to clinicopathological parameters, namely age, stage, and grade of the cancer not to mention TNBC survival. Using FGFR1 as a prognostic factor in TNBCs requires further study.

18.
Iran J Pathol ; 14(3): 232-235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583000

RESUMO

BACKGROUND & OBJECTIVE: In vascular (vasculogenic) mimicry (VM), tumoral cells mimic the endothelial cells and form the extracellular matrix-rich tubular networks. It has been proposed that VM is more extensive in aggressive tumors. This study was designed to investigate the rate of VM expression in the stromal cells of invasive ductal carcinoma (IDC) and to find its relationship with other clinicopathological factors. METHODS: In this cross-sectional study, 120 patients with histopathologic diagnosis of IDC who received mastectomy were included. The VM expression was determined by immunohistochemistry (IHC). The clinicopathologic data including age, tumor size, histological grade, clinical stage, axillary lymph node metastasis, hormonal receptors, and survival were documented. RESULTS: The mean (±SD) age of the patients was 51 (±13.83) years old. The stromal VM expression was detected in 16 of 120 patients (13.3%). Twelve specimens (75%) of positive VM expression group had grade 3 which was higher than negative VM expression group (9 cases, 8.65%; P<0.001). The VM expression showed statistically significant relationship with higher histologic grade higher clinical stage (stage 3) of the tumor (62.5% vs. 87%; P=0.003), the presence of axillary lymph node metastasis (95.6% vs. 55.8%; P<0.001), and positive HER-2 (100% vs. 31.1%; P<0.001); but not estrogen receptor (ER) or progesterone receptor (PR). However, age, tumor size and mortality rate were not significantly different among the patients with and without VM expression. CONCLUSION: The stromal VM expression showed significant relationship with higher stage and grade of the tumor and the presence of nodal metastasis. The VM expression in IDC can be used as a marker for tumor aggressiveness.

20.
Res Pharm Sci ; 14(2): 138-145, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31620190

RESUMO

Previous studies have shown that some plants in the genus of Ferula (Apiaceae) have antidiabetic effects. The present work was aimed to evaluate effects of Ferula gummosa oleo-resin in a rat model of streptozotocin-induced diabetes. Male Wistar rats were randomized into five groups (n = 6): normal control, diabetic control, diabetic rats treated with insulin (3 IU/day), and diabetic rats treated with 100 or 400 mg/kg/day of an ethanolic extract of the oleo-resin. After 4 weeks, blood samples were collected for measuring fasting blood glucose (FBG), lipid profile, aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, blood urea nitrogen, and creatinine. In addition, levels of lipid peroxidation, thiol groups, and superoxide dismutase (SOD) activity were evaluated in the liver and kidney. At the end of the fourth week, the level of FBG in rats treated with 100 mg/kg of the extract was lower than that in diabetic control rats (273 ± 39 mg/dL vs 471 ± 32 mg/dL). Administration of insulin and the extract had no significant effects on the serum lipids. Insulin and both doses of the extract significantly reduced the activity of ALT. In addition, the extract inhibited lipid peroxidation in the kidney and restored the elevated level of SOD in the liver and kidneys. Ferula gummosa oleo-resin has the potential to prevent or delay the complications of diabetes by inhibiting the progression of hyperglycemia and attenuating oxidative stress-induced damage in the liver and kidneys.

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