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1.
Pancreatology ; 24(2): 279-288, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38272717

RESUMEN

BACKGROUND: FOLFIRINOX and gemcitabine-nabpaclitaxel (GnP) are standard first-line treatment regimens for advanced pancreatic ductal adenocarcinoma (PDAC). However, currently, there is a lack of predictive biomarkers to aid in the treatment selection. We aimed to explore the prognostic and predictive value of class III ß-Tubulin (TUBB3) and human equilibrative nucleoside transporter 1 (hENT1) expression, which have previously been shown to be associated with taxane and gemcitabine resistance in advanced PDAC. METHODS: We conducted a retrospective analysis of 106 patients with advanced PDAC treated with GnP and/or FOLFIRINOX at our institution. TUBB3 and hENT1 immunohistochemical staining was performed on tumor specimens and subsequently evaluated based on the intensity and percentage of expression. RESULTS: In patients who received the GnP regimen, a high combined score (TUBB3low/hENT1high) was associated with a higher DCR and longer PFS compared to those with intermediate (TUBB3high/hENT1high or TUBB3low/hENT1low) and low score (TUBB3high/hENT1low). In the multivariate analysis, a high combined score was an independent predictor of higher DCR (OR:11.96; 95 % CI:2.61-54.82; p = 0.001) and longer PFS (HR:0.33; 95%CI:0.18-0.60; p < 0.001). However, there was no difference in response rates or PFS based on TUBB3 and hENT1 expression among patients receiving the FOLFIRINOX regimen. CONCLUSION: Our findings indicate that tumor TUBB3 and hENT1 expression may predict the efficacy of the GnP regimen, and low TUBB3 and high hENT1 expression (TUBB3low/hENT1high) are associated with a higher DCR and longer PFS in patients treated with GnP. Evaluating TUBB3 and hENT1 jointly can identify the patients most (as well as least) likely to benefit from GnP chemotherapy.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/uso terapéutico , Tranportador Equilibrativo 1 de Nucleósido/genética , Tranportador Equilibrativo 1 de Nucleósido/análisis , Gemcitabina , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Retrospectivos , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/uso terapéutico
2.
Niger J Clin Pract ; 27(4): 430-434, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38679763

RESUMEN

BACKGROUND: Various types of nasal tampons are used for packing after septoplasty. Intranasal splints are widely used as they are more advantageous than other materials regarding the lower complication rates of synechia, and lesser pain during removal. However, there is no consensus on the timing of intranasal splint removal after septoplasty operations. AIM: In this study, we aimed to investigate the effects of removal time of intranasal splints on postoperative complications after septoplasty. METHODS: One hundred patients who had septoplasty were randomly divided into two groups according to splint removal time. In group I, the splints were removed on the third postoperative day and in group II, splints were removed on the seventh postoperative day. Pain during splint removal was evaluated by visual analog scale (VAS). Complications of hemorrhage, septal hematoma, crusting, mucosal injury, and infection were recorded during splint removal and compared. In the first postoperative month, hemorrhage, crusting, mucosal injury, infection, synechia, and in the second postoperative month, synechia and perforation rates were compared between two groups. RESULTS: Mucosal crusting was significantly higher in group II during splint removal. There was no statistically significant difference between the two groups regarding the complication rates and pain scores. Our findings showed no significant difference in pain scores during splint removal and postoperative complications between the two groups except for mucosal crusting. CONCLUSION: Based on our findings, although there is no consensus on the optimal time for splint removal, earlier removal of splints can be considered a favorable option after septoplasty operations.


Asunto(s)
Tabique Nasal , Complicaciones Posoperatorias , Férulas (Fijadores) , Humanos , Femenino , Masculino , Adulto , Tabique Nasal/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Rinoplastia/efectos adversos , Rinoplastia/métodos , Factores de Tiempo , Persona de Mediana Edad , Adulto Joven , Tampones Quirúrgicos , Remoción de Dispositivos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/epidemiología , Adolescente , Dimensión del Dolor
3.
Niger J Clin Pract ; 26(6): 802-809, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37470656

RESUMEN

Background and Aim: Tyrosine kinase inhibitors (TKIs) have dramatically improved chronic myeloid leukemia (CML) prognosis. However, TKIs are associated with dyslipidemia and impaired glucosehomeostasis. Triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) is proposed to be an indicator of insulin resistance and atherogenic index, but there is no research on TG/HDL-C alterations in patients receiving TKIs for CML. We aimed to evaluate relationships between TKI type/count, clinical characteristics, and laboratory results (particularly TG/HDL-C) in CML patients. Patients and Methods: A total of 104 patients with chronic phase CML were enrolled in the study. All patients received initial imatinib therapy at 400 mg daily, the type or dose of TKI was then changed according to treatment response and clinical outcomes. Patients were compared with respect to TG/HDL-C categorization (>2.5 versus <2.5), number of TKIs used, and use of imatinib as the only TKI. Results: The median TG/HDL-C was 2.82 (1.03-17.33) and this ratio was higher than 2.5 in 59 (56.7%) patients. Patients with high TG/HDL-C had a significantly higher age than patients with low values (P < 0.001). Recipients of more than one TKI had higher EUTOS risk score and white blood cell (WBC) count (P < 0.05). Recipients of imatinib as the only TKI had higher age, low EOTUS risk score, low WBC, and low neutrophil count (all, P < 0.05). Conclusion: TG/HDL-C values were not associated with the number of different TKIs used or the use of imatinib only in chronic-phase patients with CML. Further large-scale prospective studies are needed to determine whether TG/HDL-C can be used for diagnostic or prognostic purposes in TKI recipients.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , HDL-Colesterol , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , /uso terapéutico
4.
Niger J Clin Pract ; 26(7): 921-927, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37635575

RESUMEN

Background: Type 1 fascia graft tympanoplasty (T1FGT) is the mainstay surgical approach for the treatment of tympanic membrane perforations. The most widely used graft material is temporal muscle fascia, and graft take rates are reported differently. The methods to enhance graft take are still being investigated. Aim: The aim of our study was to investigate the effect of titanium-prepared platelet-rich fibrin (T-PRF) on graft take and hearing outcomes in T1FGT. Materials and Methods: Fifty-seven ears eligible for T1FGT were involved in the study and prospectively evaluated. T-PRF was applied with T1FGT in 27 ears. Thirty ears in the other group underwent only T1FGT. The patients underwent an otomicroscopic and audiometric examination in preoperative and postoperative 2nd week, 1st month, and 6th month. Both groups were evaluated in terms of hearing levels, infection, and graft take rates. Results: Two patients in the T1FGT + T-PRF group and seven patients in the T1FGT group had postoperative perforation (graft take rate: 92.6% versus 76.7%). The graft take rate was found to be increased in the T-PRF group although the difference was not statistically significant. In the T1FGT group, the percentage of infection was higher than in the T1FGT + T-PRF group. When the preoperative and postoperative 6th-month audiometry was compared, a statistically significant hearing gain was obtained for both groups. Conclusion: In the treatment of tympanic membrane perforations, T-PRF applied over the fascia graft was shown to increase graft take rates and decrease the probability of infection. Further studies with larger samples are needed to demonstrate the effects of PRF.


Asunto(s)
Fibrina Rica en Plaquetas , Perforación de la Membrana Timpánica , Humanos , Titanio , Supervivencia de Injerto , Timpanoplastia , Audición , Perforación de la Membrana Timpánica/cirugía , Fascia
5.
Nat Methods ; 16(1): 111-116, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30532080

RESUMEN

Preprocessing of functional magnetic resonance imaging (fMRI) involves numerous steps to clean and standardize the data before statistical analysis. Generally, researchers create ad hoc preprocessing workflows for each dataset, building upon a large inventory of available tools. The complexity of these workflows has snowballed with rapid advances in acquisition and processing. We introduce fMRIPrep, an analysis-agnostic tool that addresses the challenge of robust and reproducible preprocessing for fMRI data. fMRIPrep automatically adapts a best-in-breed workflow to the idiosyncrasies of virtually any dataset, ensuring high-quality preprocessing without manual intervention. By introducing visual assessment checkpoints into an iterative integration framework for software testing, we show that fMRIPrep robustly produces high-quality results on a diverse fMRI data collection. Additionally, fMRIPrep introduces less uncontrolled spatial smoothness than observed with commonly used preprocessing tools. fMRIPrep equips neuroscientists with an easy-to-use and transparent preprocessing workflow, which can help ensure the validity of inference and the interpretability of results.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Flujo de Trabajo , Mapeo Encefálico/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Reproducibilidad de los Resultados
6.
Ann Surg Oncol ; 29(10): 6327-6336, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35876920

RESUMEN

BACKGROUND: One fourth of early-stage breast cancer cases become metastatic during the follow-up period. Limited metastasis is a metastatic disease condition in which the number of metastatic sites and the extent of the disease both are limited, and the disease is amenable to metastatic intervention. This prospective study aimed to evaluate intervention for limited metastases in the lung, liver, or both. METHODS: The study enrolled luminal A/B and/or human epidermal growth factor receptor 2 (HER2)-neu+ patients with operable lung and/or liver metastases in the follow-up assessment after completion of primary breast cancer treatment and patients with a diagnosis of metastasis after 2014. Demographic, clinical, tumor-specific, and metastasis detection-free interval (MDFI) data were collected. Bone metastasis in addition to lung and liver metastases also was included in the analysis. The patients were divided into two groups according to the method of treatment for metastases: systemic therapy alone (ST) group or intervention (IT) group. RESULTS: Until June 2020, 200 patients were enrolled in the study. The demographic data were similar between the two groups. The median follow-up time was 77 months (range 55-107 months) in the IT group (n = 119; 59.5%) and 57 months (range 39-84) in the ST-only group (n = 81; 40.5%). The median MDFI was 40 months (range 23-70 months) in the IT group, and 35 months (range 13-61 months) in the ST-only group (p = 0.47). The groups had similar surgeries for the primary tumor and axilla. Most of the patients had liver metastases (49.5%, n = 99), and 42% (n = 84) of the patients had lung metastases. Both lung and liver metastases were found in 8.5% (n = 17) of the patients. The primary tumor was estrogen receptor/progesterone receptor-positive in 75% (n = 150) of the patients, and 32% (n = 64) of the patients had HER2-neu+ tumors. Metastatic-site resection was performed for 32% (n = 64) of the patients, and 27.5% (n = 55) of the patients underwent metastatic ablative interventions. In the Kaplan-Meier survival analysis, the hazard of death (HoD) was 56% lower in the IT group than in the ST-only group (hazard ratio [HR], 0.44; 95% confidence interval [CI] 0.26-0.72; p = 0.001). The HoD was lower in the IT group than in the ST-only group for the patients younger than 55 years (HR, 0.32; 95% CI 0.17-0.62; p = 0.0007). In the multivariable Cox regression model, HoD was significantly lower for the patients who underwent intervention for metastases and had an MDFI longer than 24 months, but their liver metastases doubled the risk of death compared with lung metastases. CONCLUSION: Metastasis-directed interventions have reduced the risk of death for patients with limited lung/liver metastases who are amenable to interventions after completion of primary cancer treatment. For a select group of patients, such as those with luminal A/B or HER2-neu+ breast cancer who are younger than 55 years with limited metastases to the lung and liver or an MDFI longer than 24 months, surgical or ablative therapy for metastases should be considered and discussed on tumor boards.


Asunto(s)
Neoplasias de la Mama , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Histamina/análogos & derivados , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Pronóstico , Estudios Prospectivos , Receptor ErbB-2/metabolismo , Sistema de Registros , Estudios Retrospectivos
8.
Genet Mol Res ; 14(1): 1000-7, 2015 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-25730039

RESUMEN

Rheumatoid arthritis (RA) is a major cause of adult chronic inflammatory arthritis and an autoimmune disease of unknown etiology in which the inflammatory pathology involves T cell activation. Genetic mutations in the Mediterranean fever (MEFV) gene, encoding pyrin, influence the severity of RA, but the underlying mechanisms are not completely understood. In this study, we investigated whether the full-length MEFV gene (MEFV-fl) and the exon 2-deleted splice isoform (MEFV-d2) expression are associated with or responsible for the clinical conditions of RA. This study include 47 patients with RA and 47 age- and gender-matched healthy controls. Quantitative real-time polymerase chain reaction analysis was performed to examine transcriptional changes in MEFV gene expression from peripheral blood samples. Reverse transcription-polymerase chain reaction of peripheral blood cells revealed the downregulation of MEFV-fl mRNA in non-treated patients compared with healthy controls and treated patients. MEFV-d2 expression was not different between groups. This is the first study to investigate the expression of MEFV transcript in RA. Deregulation of the MEFV gene is likely to result in uncontrolled inflammation as observed in RA. Therefore, downregulation of MEFV-fl may be involved in the pathogenesis of early-stage RA and treatment and may ameliorate MEFV-fl expression.


Asunto(s)
Artritis Reumatoide/genética , Proteínas del Citoesqueleto/genética , Regulación de la Expresión Génica/genética , Predisposición Genética a la Enfermedad , Adulto , Anciano , Artritis Reumatoide/patología , Proteínas del Citoesqueleto/biosíntesis , Exones , Femenino , Estudios de Asociación Genética , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Mutación , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , Pirina , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Factores de Riesgo
9.
Bratisl Lek Listy ; 116(6): 379-82, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26084740

RESUMEN

The prominent cells in the late phase of wound healing during proliferation and matrix deposition are fibroblasts. Foreign materials in the operation site like prosthesis prolong the inflammation and induce fibroblast proliferation (8). 3 different prostheses used in this study induced chronic inflammation and fibrosis and provided an effective repair. Dense and thick adhesions due to fibrosis also induced strong adhesions to omentum and small intestine if only polypropylene mesh used for hernia repair. However, there was no difference between SprayGel treated polypropylene mesh and Sepramesh when compared for fibrosis. It also prevents the intraabdominal adhesion formation. It is nontoxic, sticky adherent, non- immigrant and easy to use both in open and laparoscopic surgeries. This experimental study revealed that polyethyleneglycol applied polypropylene mesh accomplishes hernia repair with significantly less adhesion formation than polypropylene mesh alone while securing a remarkable economy than adhesion barrier coated dual meshes (Tab. 6, Fig. 7, Ref. 23). Text in PDF www.elis.sk.


Asunto(s)
Materiales Biocompatibles Revestidos , Herniorrafia/métodos , Enfermedades Peritoneales/prevención & control , Polietilenglicoles/uso terapéutico , Polipropilenos , Mallas Quirúrgicas , Animales , Enfermedades Peritoneales/patología , Ratas , Adherencias Tisulares/patología , Adherencias Tisulares/prevención & control
10.
Clin Exp Dermatol ; 39(2): 176-81, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24033834

RESUMEN

BACKGROUND: Scleroderma is a chronic inflammatory disease characterized by widespread fibrosis of the skin and the internal organs. Ghrelin is a polypeptide hormone produced by various tissues and inflammatory cells. In experimental studies, ghrelin has been shown to have anti-inflammatory and antioxidant effects, in addition to its metabolic actions. AIM: To evaluate the potential preventive effects of ghrelin on a mouse model of bleomycin (BLM)-induced scleroderma. METHODS: This study involved five groups of BALB/c mice (n = 7 in each group). Mice in the control group received 100 µL/day of phosphate-buffered saline (PBS) subcutaneously, while the other four groups were given 100 µg/day of BLM (dissolved in 100 µL PBS) subcutaneously. Three of the BLM-treated groups received intraperitoneal doses (10 ng/kg/day) of acylated, nonacylated or total ghrelin. Animals were killed at the end of the fourth week, and blood and tissue samples were collected for further analysis. Dermal thickness, serum levels of transforming growth factor-ß1, numbers of inflammatory cells on the dermal layer and numbers of α-smooth muscle actin-positive cells were determined. RESULTS: BLM increased dermal thickness, numbers of inflammatory cells on the dermal layer and activity of the myofibroblastic cells. Application of acylated, nonacylated and total ghrelin decreased the infiltration of inflammatory cells and the activity of the myofibroblastic cells, and reduced dermal fibrosis. CONCLUSIONS: Based on these results, it appears that ghrelin has an antifibrotic action, in addition to the anti-inflammatory and antioxidant effects that have been documented previously. The pathogenic and therapeutic roles of ghrelin in scleroderma should be evaluated by further studies.


Asunto(s)
Antiinflamatorios/uso terapéutico , Ghrelina/uso terapéutico , Esclerodermia Localizada/tratamiento farmacológico , Análisis de Varianza , Animales , Antibióticos Antineoplásicos , Bleomicina , Modelos Animales de Enfermedad , Femenino , Fibrosis/prevención & control , Ratones , Ratones Endogámicos BALB C , Esclerodermia Localizada/inducido químicamente , Esclerodermia Localizada/patología
11.
Minerva Chir ; 69(3): 147-53, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24970303

RESUMEN

AIM: We evaluated the prognostic significance of preoperative serum albumin value and metastatic lymph node ratio for gastric cancer patients. METHODS: We studied patients diagnosed with gastric carcinoma in the first Department of Surgery, Bezmialem Vakif Gureba Training and Research Hospital between January 2004 and December 2010; the patients were studied retrospectively. RESULTS: A total of 67 patients with a mean age of 58.7 ± 11.4 years were included in the study. The majority of patients were male (N.=53 male; N.=14 female). Most patients were in an advanced stage of the disease (stage III-IV) on admission (67.2%). We classified patients according to albumin value as "normal" Group 1 (83%) and "hypoalbuminemic" Group 2 (17%). With albumin, age, resection type, perineural invasion, and ratio of metastatic lymph nodes, T and TNM stages were significant predictors of cancer-specific survival. CONCLUSION: As a result, irrespective of mechanism, pre-operative evaluations of albumin and metastatic lymph node ratio should be performed to stratify the patients for risk analysis and prognosis. A level less than 3.5 g/dL is a negative prognostic factor for resectable gastric cancers.


Asunto(s)
Albúminas/metabolismo , Biomarcadores de Tumor/sangre , Carcinoma/diagnóstico , Carcinoma/secundario , Ganglios Linfáticos/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/secundario , Anciano , Carcinoma/sangre , Carcinoma/mortalidad , Carcinoma/cirugía , Femenino , Estudios de Seguimiento , Gastrectomía , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Neoplasias Gástricas/sangre , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Resultado del Tratamiento
12.
Acta Chir Belg ; 113(4): 258-62, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24224434

RESUMEN

BACKGROUND: Here, we present our experience of 12 lung cancer cases operated with carinal sleeve pneumonectomy (CSP) from 2001 to 2011. METHODS: 12 cases who had undergone CSP in our department from 2001 to 2011 were retrospectively evaluated and presented by taking into account their demographical and clinical features, the surgical technique that was used, the complications that developed and the latest conditions of these patients. RESULTS: Of the 12 cases, 11 were male and 1 was female with a mean age of 58.6 years (40-71 years). 11 cases had right and 1 had left CSP. The ethiology for resection was lung cancer in all cases. 10 cases had carinal invasion of the lung cancer, 1 had bronchopleural fistula developing after right pneumonectomy, 1 had distal tracheal rupture due to intubation tube placed during pneumonectomy; these all resulted in performing CSP. Five patients developed complications during the postoperative period. Three cases developed recurrences/metastases during the follow-up. Nine patients died, 3 patients were alive and were followed-up by our department. For all the cases, the median survival was 9 months, the estimated survival rate of 2-years was 33%, and 5-year survival rate was 22%. Survival for 2-4 years was 71%. CONCLUSIONS: We think that with increasing surgical experience better results are obtained in these technically demanding procedures.


Asunto(s)
Carcinoma Broncogénico/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Complicaciones Posoperatorias/mortalidad , Adulto , Anciano , Broncoscopía , Carcinoma Broncogénico/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Mediastinoscopía , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonectomía/mortalidad , Tomografía de Emisión de Positrones , Radiografía Torácica , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Turquía/epidemiología
13.
B-ENT ; 9(2): 122-31, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23909119

RESUMEN

OBJECTIVE: The purpose of this study is to describe the results of universal newborn hearing screening (UNHS) in 2229 newborns and to assess the effectiveness of a two-stage automated transient evoked otoacoustic emission (a-TEOAE) test protocol. MATERIALS AND METHODS: Between May 2007 and January 2008, a universal newborn hearing screening program, instituting two-stage a-TEOAE, was evaluated. The hearing status of the newborns who failed the two-stage screening tests were evaluated with the auditory brainstem response (ABR) test during the diagnostic stage. The risk factors for hearing loss determined by the Joint Committee on Infant Hearing Loss (JCIH) and prematurity, consanguineous marriage, and birth type as presumptive risk factors were recorded. RESULTS: During the study period, 2229 newborns were screened. Sensorineural hearing loss (SNHL) was identified in 8 newborns. Fourteen newborns were lost to follow-up. One hundred thirty six newborns were high-risk neonatal intensive care unit (NICU) patients. The prevalence of SNHL was 2.9% (4/136) in NICU newborns, and 0.19% (4/2079) in the well-baby nursery. SNHL prevalence in the study group overall was found to be 0.36% (8/2215). Craniofacial anomalies and family history of hearing loss were found to be significantly related to SNHL in newborns. Prematurity and consanguinity that are not listed among JCIH risk factors were also found to be statistically significantly related with SNHL. CONCLUSIONS: This is the first report of a universal hearing screening program in the Eastern Black Sea region of Turkey. Two-stage a-TEOAE is an efficient and feasible hospital-based screening protocol in newborns.


Asunto(s)
Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/epidemiología , Tamizaje Neonatal , Emisiones Otoacústicas Espontáneas , Humanos , Recién Nacido , Prevalencia , Factores de Riesgo , Turquía/epidemiología
14.
Clin Exp Dermatol ; 37(1): 48-54, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22182434

RESUMEN

BACKGROUND: T lymphocytes induce the transformation of fibroblasts into myofibroblasts, the main mediators of fibrogenesis. The inosine 5'-monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF) and the anti-CD25 monoclonal antibody daclizumab (DCZ) have been reported to suppress the proliferation of T lymphocytes. AIM: To evaluate the preventive effects of MMF and DCZ in early stages of bleomycin (BLM)-induced scleroderma. METHODS: This study involved five groups of Balb/c mice (n = 10 per group). Mice in four of the groups were injected subcutaneously (SC) with BLM [100 µg/day in 100 µL phosphate-buffered saline (PBS)] for 4 weeks; the remaining (control) group received only 100 µL PBS. Three of the BLM-treated groups also received either intraperitoneal MMF 50 or 150 mg/kg/day, or SC DCZ 100 µg/week. At the end of the fourth week, all mice were killed, and blood and tissue samples were obtained for further analysis. RESULTS: In the BLM-treated group, increases were seen in inflammatory-cell infiltration, α-smooth muscle actin-positive (α-SMA+) fibroblastic cell count, tissue hydroxyproline content, and dermal thickness. Dermal fibrosis was histopathologically prominent. In BLM-treated mice also given MMF or DCZ, inflammatory-cell infiltration, tissue hydroxyproline content and dermal thickness were decreased. In the MMF groups, decreases were also noted in α-SMA+ fibroblastic cell count. CONCLUSION: In this BLM-induced dermal fibrosis model, MMF and DCZ treatments prevented the development of dermal fibrosis. Further studies are needed to evaluate whether targeting T lymphocytes is effective in resolving pre-existing fibrosis in human scleroderma.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Inmunoglobulina G/farmacología , Inmunosupresores/farmacología , Ácido Micofenólico/análogos & derivados , Esclerodermia Localizada/prevención & control , Animales , Antibióticos Antineoplásicos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bleomicina , Citocinas/metabolismo , Daclizumab , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Hidroxiprolina/análisis , Inmunoglobulina G/uso terapéutico , Inmunohistoquímica , Inmunosupresores/uso terapéutico , Inyecciones Subcutáneas , Ratones , Ratones Endogámicos BALB C , Ácido Micofenólico/farmacología , Ácido Micofenólico/uso terapéutico , Esclerodermia Localizada/inducido químicamente , Esclerodermia Localizada/metabolismo , Esclerodermia Localizada/patología , Piel/química , Piel/patología
15.
Indian J Med Res ; 135(5): 656-61, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22771595

RESUMEN

BACKGROUND & OBJECTIVES: Translocation of bacteria from the gut is an important factor in the development of septic complications and mortality in acute pancreatitis (AP). The present study was designed to assess the effects of infliximab treatment on bacterial translocation (BT) in experimental acute necrotizing pancreatitis. METHODS: Male Sprague-Dawley rats (n=45) were allocated into three groups. AP was induced in group II (positive control, n=15) and group III (Infliximab; n=15) by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (Sham; n=15) received normal saline infusion into the common biliopancreatic duct as placebo. Groups I and II were treated by normal saline and group III was treated with infliximab intraperitoneally on 6, 30 and 54 h after induction of pancreatitis. All surviving animals were killed 60 h after the induction of pancreatitis, and specimens were collected for amylase measurement as well as histopathologic and microbiologic examinations. RESULTS: Oedema, acinar cell necrosis, inflammatory infiltration, haemorrhage, fat necrosis and perivascular inflammation in group III rats were decreased with infliximab treatment when compared with group II (P<0.001). BT to mesentery lymph node in groups I, II and III were 20, 100 and 46 per cent, respectively. BT to peritoneum and pancreas in group III was lower than group II (P<0.05). INTERPRETATION & CONCLUSIONS: Infliximab administration resulted in beneficial effects on BT and histopathologic changes in the experimental necrotizing pancreatitis. Whether anti-TNF therapy has a role in prevention of complications of ANP needs to be established.


Asunto(s)
Anticuerpos Monoclonales , Traslocación Bacteriana , Pancreatitis Aguda Necrotizante , Células Acinares/patología , Amilasas/sangre , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Traslocación Bacteriana/efectos de los fármacos , Humanos , Infliximab , Masculino , Modelos Animales , Conductos Pancreáticos/microbiología , Pancreatitis Aguda Necrotizante/inducido químicamente , Pancreatitis Aguda Necrotizante/microbiología , Pancreatitis Aguda Necrotizante/patología , Ratas , Ratas Sprague-Dawley , Ácido Taurocólico/farmacología
16.
SAR QSAR Environ Res ; 33(3): 193-214, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35243936

RESUMEN

Some novel substituted thiazolylhydrazine derivatives were designed, synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes and antioxidant activities were investigated. The structures of the synthesized compounds were determined using different spectroscopic techniques such as 1H-NMR, 13C-NMR, and HRMS. According to the enzyme inhibition results, the synthesized compounds showed selectivity against BuChE enzyme inhibition. Compounds 5e, 5g, 5i and 5j displayed significant BuChE inhibition potencies. Among them, compound 5i was found to be the most effective derivative with an IC50 value of 56.01 ± 0.054 µM. In addition, their antioxidant properties were evaluated in vitro through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. For compounds 5e, 5g, 5i and 5j in silico molecular docking and 100 ns molecular dynamics simulations studies against the BuChE enzyme were performed to determine possible protein-ligand interactions and stability. DFT-D3 study was performed to stabilize of compounds 5e, 5g, 5i and 5j both in gas and solvent medium and investigated their electronic properties. Of all geometries, that of DMSO is the lowest one.


Asunto(s)
Acetilcolinesterasa , Enfermedad de Alzheimer , Acetilcolinesterasa/metabolismo , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Humanos , Hidrazonas/farmacología , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad Cuantitativa , Relación Estructura-Actividad
17.
SAR QSAR Environ Res ; 33(11): 899-914, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36420624

RESUMEN

A series of some new benzimidazole-1,3,4-thiadiazoles was synthesized. The structures of target substances were confirmed by using 1H-NMR and 13С-NMR spectroscopy, mass spectrometry and elemental analysis. The synthesized compounds were evaluated for antimicrobial activity against six bacterial strains namely Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 2942), Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 29213)and four fungal strains namely Candida albicans (ATCC 24433), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019) and Candida glabrata (ATCC 9). Antimicrobial data revealed that compounds 4f and 4i with MIC of < 0.97 µg/mL were found to be most effective against E. coli. Among the studied molecules, compounds 4f and 4i showed the best antifungal activity with MIC value of 1.95 µg/mL. Additionally, docking studies were performed towards the most promising compounds 4f and 4i, in the active site of DNA gyrase revealing strong interactions. A molecular dynamics (MD) simulation analysis was also used to investigate the dynamic nature, binding interaction, and protein-ligand stability.


Asunto(s)
Antiinfecciosos , Tiadiazoles , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Escherichia coli , Relación Estructura-Actividad Cuantitativa , Antiinfecciosos/farmacología , Antibacterianos , Tiadiazoles/farmacología , Bencimidazoles/farmacología , Candida albicans
18.
Eur Rev Med Pharmacol Sci ; 26(14): 5178-5185, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35916815

RESUMEN

OBJECTIVE: Detection of the Kayser-Fleischer (KF) ring in the diagnostic scoring and treatment follow-up of Wilson's Disease (WD) is important. Slit lamp (SL) biomicroscopic examination has traditionally been used in the evaluation of the KF ring. The role of Anterior Segment Optical Coherence Tomography (AS-OCT), which is used in various corneal diseases, in the detection of KF rings has attracted attention in recent years. In our study, we tried to demonstrate the effectiveness of AS-OCT in detecting the KF ring by comparing it with SL biomicroscopic examination. PATIENTS AND METHODS: 64 of 356 patients followed in our outpatient clinic due to WD were included in the study in the order of their admission to the outpatient clinic. The KF ring was evaluated in both eyes by SL-biomicroscopic examination and AS-OCT. Ophthalmic examination, and findings were performed by the same physician. RESULTS: Age range was 18-67 years, mean 33.06±10.83 years, gender was 39.1% (n: 25) female. At the time of diagnosis, the mean age was 19.48 ± 9.36 years, range was minimum 5 years and maximum 51 years. Clinical presentation was mixed type involvement n: 18 (28.1%), hepatic involvement n: 32 (50%), neurological involvement n: 14 (21.9%). The follow-up period was 2-257 months (74.6±76.16). The presence of KF ring was evaluated together with both AS-OCT and slit-lamp examination, the presence of KF could be detected in both AS-OCT and SL biomicroscopic examination in 10 patients (15.6%), in 12 (18.8%) of the cases KF ring is positive in AS-OCT but was negative in Slit-lamp biomicroscopic examination, in 65.6 (n: 42) of the cases OCT and slit-lamp biomicroscopic examination results were negative. CONCLUSIONS: The sensitivity of AS-OCT in detecting the KF ring was higher than the slit-lamp biomicroscopic examination. AS-OCT can detect early stage of KF rings in Wilson's Disease patients, so that diagnosis and treatment accuracy can be evaluated effectively.


Asunto(s)
Enfermedades de la Córnea , Degeneración Hepatolenticular , Adolescente , Adulto , Anciano , Preescolar , Cobre , Enfermedades de la Córnea/diagnóstico por imagen , Femenino , Degeneración Hepatolenticular/diagnóstico por imagen , Degeneración Hepatolenticular/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Tomografía de Coherencia Óptica/métodos , Adulto Joven
19.
Reprod Biomed Online ; 18(4): 455-9, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19400984

RESUMEN

Hypogonadotrophic hypogonadism is characterized by oligospermia or azoospermia and low testosterone, FSH and LH concentrations. In such cases, treatment with gonadotrophins is required to produce or increase spermatozoa in the ejaculate but few achieve normal spermatogenesis. After long periods of medical treatment, if the patients still have a low sperm count or azoospermia, assisted reproductive technologies in addition to hormone administration can be offered. Four cases of hypogonadotrophic hypogonadism with persistent azoospermia after at least 10 months of medical treatment are reported. In all four cases, spermatozoa retrieved by testicular sperm extraction and intracytoplasmic sperm injection (ICSI) were used to achieve fertilization. Excess spermatozoa were frozen in all cases. Six ICSI cycles using fresh testicular spermatozoa in four and thawed testicular spermatozoa in two were performed. Although there was no pregnancy in cycles where thawed spermatozoa were used, three clinical pregnancies were achieved in four cycles using fresh testicular spermatozoa. One of them ended with spontaneous abortion at 10 weeks of gestation and the two others resulted in the delivery of three normal offspring. If azoospermia persists after medical treatment, spermatozoa can be obtained surgically from testes and can be used successfully to achieve pregnancy in cases of hypogonadotrophic hypogonadism.


Asunto(s)
Azoospermia/terapia , Gonadotropinas/uso terapéutico , Hipogonadismo/tratamiento farmacológico , Inyecciones de Esperma Intracitoplasmáticas , Espermatogénesis/efectos de los fármacos , Testículo/citología , Adulto , Azoospermia/etiología , Femenino , Hormonas Gonadales/sangre , Gonadotropinas/farmacología , Humanos , Hipogonadismo/complicaciones , Masculino , Embarazo , Resultado del Embarazo
20.
Reprod Biomed Online ; 19(4): 472-7, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19909586

RESUMEN

This study was designed to evaluate the effect of luteal-phase administration of single-dose gonadotrophin-releasing hormone (GnRH) agonist on pregnancy, implantation and live birth rates in patients who received GnRH antagonist for pituitary suppression. The study population consisted of 164 patients who underwent intracytoplasmic sperm injection (ICSI) after ovulation induction by gonadotrophins and GnRH antagonist for the prevention of a premature LH surge. For luteal-phase support, all the cases received intravaginal 600 mg micronized progesterone. In this prospective study, patients were randomly assigned to two groups. In one group, patients received an additional single dose of GnRH agonist (0.5 mg leuprolide acetate) subcutaneously on day 6 after ICSI, whereas the patients in the other group did not. Although the number of embryos transferred and the grade of the embryos were similar in the two groups, the patients in the luteal-phase agonist group had significantly higher rates of implantation and clinical pregnancy rates ( P < 0.05). When the two groups were compared, there were also statistically significant differences in multiple pregnancy and live birth rates ( P < 0.05). Administration of single-dose GnRH agonist as a luteal-phase support in ovarian stimulation-GnRH antagonist cycles in addition to standard luteal support seems to be effective in all cycle outcome parameters.


Asunto(s)
Hormona Liberadora de Gonadotropina/agonistas , Adulto , Femenino , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Humanos , Fase Luteínica/efectos de los fármacos , Embarazo , Estudios Prospectivos , Resultado del Tratamiento
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