RESUMO
Cisplatin-induced renal tubular injury largely restricts the wide-spread usage of cisplatin in the treatment of malignancies. Identifying the key signaling pathways that regulate cisplatin-induced renal tubular injury is thus clinically important. PARVB, a focal adhesion protein, plays a crucial role in tumorigenesis. However, the function of PARVB in kidney disease is largely unknown. To investigate whether and how PARVB contributes to cisplatin-induced renal tubular injury, a mouse model (PARVB cKO) was generated in which PARVB gene was specifically deleted from proximal tubular epithelial cells using the Cre-LoxP system. In this study, we found depletion of PARVB in proximal tubular epithelial cells significantly attenuates cisplatin-induced renal tubular injury, including tubular cell death and inflammation. Mechanistically, PARVB associates with transforming growth factor-ß-activated kinase 1 (TAK1), a central regulator of cell survival and inflammation that is critically involved in mediating cisplatin-induced renal tubular injury. Depletion of PARVB promotes cisplatin-induced TAK1 degradation, inhibits TAK1 downstream signaling, and ultimately alleviates cisplatin-induced tubular cell damage. Restoration of PARVB or TAK1 in PARVB-deficient cells aggravates cisplatin-induced tubular cell injury. Finally, we demonstrated that PARVB regulates TAK1 protein expression through an E3 ligase ITCH-dependent pathway. PARVB prevents ITCH association with TAK1 to block its ubiquitination. Our study reveals that PARVB deficiency protects against cisplatin-induced tubular injury through regulation of TAK1 signaling and indicates targeting this pathway may provide a novel therapeutic strategy to alleviate cisplatin-induced kidney damage.
Assuntos
Cisplatino , MAP Quinase Quinase Quinases , Camundongos Knockout , Transdução de Sinais , Cisplatino/efeitos adversos , Cisplatino/toxicidade , Animais , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , Transdução de Sinais/efeitos dos fármacos , Camundongos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Antineoplásicos/farmacologia , Antineoplásicos/efeitos adversos , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de SinalRESUMO
Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion. We found that migfilin is associated with SNAP29 and Vamp8, thereby facilitating Stx17-SNAP29-Vamp8 SNARE complex assembly. Depletion of migfilin disrupted the formation of the SNAP29-mediated SNARE complex, which consequently blocked the autophagosome-lysosome fusion, ultimately suppressing cancer cell growth. Restoration of the SNARE complex formation rescued migfilin-deficiency-induced autophagic flux defects. Finally, we found depletion of migfilin inhibited cancer cell proliferation. SNARE complex reassembly successfully reversed migfilin-deficiency-induced inhibition of cancer cell growth. Taken together, our study uncovers a new function of migfilin as an autophagy-regulatory protein and suggests that targeting the migfilin-SNARE assembly could provide a promising therapeutic approach to alleviate cancer progression.
Assuntos
Autofagia , Moléculas de Adesão Celular , Proliferação de Células , Lisossomos , Proteínas Qb-SNARE , Proteínas Qc-SNARE , Proteínas R-SNARE , Humanos , Proteínas R-SNARE/metabolismo , Proteínas R-SNARE/genética , Proteínas Qb-SNARE/metabolismo , Proteínas Qb-SNARE/genética , Proteínas Qc-SNARE/metabolismo , Proteínas Qc-SNARE/genética , Lisossomos/metabolismo , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , Autofagossomos/metabolismo , Células HeLa , Linhagem Celular Tumoral , Ligação Proteica , Proteínas SNARE/metabolismo , Proteínas SNARE/genética , Fusão de Membrana , Proteínas Qa-SNARERESUMO
Rationale: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid tumor, with extremely low survival rates. Identifying key signaling pathways driving PDAC progression is crucial for the development of therapies to improve patient response rates. Kindlin-2, a multi-functional protein, is involved in numerous biological processes including cell proliferation, apoptosis and migration. However, little is known about the functions of Kindlin-2 in pancreatic cancer progression in vivo. Methods: In this study, we employ an in vivo PDAC mouse model to directly investigate the role of Kindlin-2 in PDAC progression. Then, we utilized RNA-sequencing, the molecular and cellular assays to determine the molecular mechanisms by which Kindlin-2 promotes PDAC progression. Results: We show that loss of Kindlin-2 markedly inhibits KrasG12D-driven pancreatic cancer progression in vivo as well as in vitro. Furthermore, we provide new mechanistic insight into how Kindlin-2 functions in this process, A fraction of Kindlin-2 was localized to the endoplasmic reticulum and associated with the RNA helicase DDX3X, a key regulator of mRNA translation. Loss of Kindlin-2 blocked DDX3X from binding to the 5'-untranslated region of c-Myc and inhibited DDX3X-mediated c-Myc translation, leading to reduced c-Myc-mediated glucose metabolism and tumor growth. Importantly, restoration of the expression of either the full-length Kindlin-2 or c-Myc, but not that of a DDX3X-binding-defective mutant of Kindlin-2, in Kindlin-2 deficient PDAC cells, reversed the inhibition of glycolysis and pancreatic cancer progression induced by the loss of Kindlin-2. Conclusion: Our studies reveal a novel Kindlin-2-DDX3X-c-Myc signaling axis in PDAC progression and suggest that inhibition of this signaling axis may provide a promising therapeutic approach to alleviate PDAC progression.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Camundongos , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas c-myc , Transdução de Sinais , Neoplasias PancreáticasAssuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Liraglutida/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
Glomerular diseases afflict millions of people and impose an enormous burden on public healthcare costs worldwide. Identification of potential therapeutic targets for preventing glomerular diseases is of considerable clinical importance. CHILKBP is a focal adhesion protein and modulates a wide array of biological functions. However, little is known about the role of CHILKBP in glomerular diseases. To investigate the function of CHILKBP in maintaining the structure and function of podocytes in a physiologic setting, a mouse model (CHILKBP cKO) was generated in which CHILKBP gene was conditionally deleted in podocytes using the Cre-LoxP system. Ablation of CHILKBP in podocytes resulted in massive proteinuria and kidney failure in mice. Histologically, typical podocyte injury including podocyte loss, foot process effacement, and glomerulosclerosis was observed in CHILKBP cKO mice. Mechanistically, we identified ZO-1 as a key junctional protein that interacted with CHILKBP. Loss of CHILKBP in podocytes exhibited a significant reduction of ZO-1 expression, leading to abnormal actin organization, aberrant slit diaphragm protein expression and compromised podocyte filtration capacity. Restoration of CHILKBP or ZO-1 in CHILKBP-deficient podocytes effectively alleviated podocyte injury induced by the loss of CHILKBP in vitro and in vivo. Finally, we showed the glomerular expression of CHILKBP and ZO-1 was decreased in patients with proteinuric kidney diseases. Our findings reveal a novel signaling pathway consisting of CHILKBP and ZO-1 that plays an essential role in maintaining podocyte homeostasis and suggest novel therapeutic approaches to alleviate glomerular diseases.
Assuntos
Nefropatias , Podócitos , Camundongos , Animais , Podócitos/metabolismo , Glomérulos Renais/metabolismo , Nefropatias/metabolismo , Transdução de Sinais , Proteinúria/metabolismoRESUMO
Recent development in proteomic sample preparation using nanofluidic devices has made single-cell proteome profiling possible. However, these nanofluidic devices require special expertise and costly nanopipetting instruments. They are also specially designed for single cells, are not well-suited for profiling rare samples consisting of a few hundred mammalian cells, arguably a more common need that remains a great challenge. Herein, we developed an easy-to-use and scalable device for processing low-input samples, which combined the merits of previously reported rare cell proteomic reactor (RCPR) and mixed-mode simple and integrated spintip-based proteomics technology, as an alternative to nanofluidic devices. All steps of proteomics sample preparation, including protein preconcentration, impurity removal, reduction, alkylation, digestion, and desalting, were fully integrated in our workflow, and the device can be directly connected to online nanoLC-MS system after processing the rare samples. Using the developed 3-frit mixed-mode RCPR, we identified on average 946 ± 158, 2 998 ± 106, and 3 934 ± 85 protein groups in data-dependent acquisition (DDA) mode from 10, 100, and 500 fluorescence-activated cell sorting (FACS)-sorted 293T cells, respectively. As an illustrative application of this technology, we performed a label-free proteome comparison of 500 FACS-sorted mouse cochlear hair cells of two different ages. On average, 2 595 ± 230 and 2 042 ± 120 protein groups were quantified in the juvenile and the adult samples in DDA mode, respectively, achieving dynamic ranges of over 6 orders of magnitude for both.
Assuntos
Proteoma , Proteômica , Animais , Camundongos , Citometria de Fluxo , MamíferosRESUMO
The information of occlusion culling in the spherical holography has been ignored or discarded for a long time. However, the information of the occlusion could be utilized, which has never been considered before. In this paper, a spherical crown diffraction model for a curved holographic display is proposed by occlusion utilizing. In the proposed spherical crown diffraction model, the method of occlusion utilizing is realized firstly, which is based on an optical-path-select function to remain the desired light information. Based on the method of occlusion utilizing, a spherical crown diffraction model for curve holographic display is proposed by further analyzing the optical propagation geometry relationship. This proposed diffraction model not only retains the advantage of a conventional diffraction model with a large view angle of 360°in the azimuth direction, but also improves the view angle in the latitude direction. Besides, the proposed model by occlusion utilizing has higher optical utilization than that model by occlusion culling. Furthermore, the effectiveness and feasibility of the proposed model are verified by numerical simulations. To our knowledge, it is the first time that a method and an application are proposed to utilize the occlusion.
RESUMO
Androgen receptor (AR) signaling plays important roles in breast cancer progression. We show here that Kindlin-2, a focal adhesion protein, is critically involved in the promotion of AR signaling and breast cancer progression. Kindlin-2 physically associates with AR and Src through its two neighboring domains, namely F1 and F0 domains, resulting in formation of a Kindlin-2-AR-Src supramolecular complex and consequently facilitating Src-mediated AR Tyr-534 phosphorylation and signaling. Depletion of Kindlin-2 was sufficient to suppress Src-mediated AR Tyr-534 phosphorylation and signaling, resulting in diminished breast cancer cell proliferation and migration. Re-expression of wild-type Kindlin-2, but not AR-binding-defective or Src-binding-defective mutant forms of Kindlin-2, in Kindlin-2-deficient cells restored AR Tyr-534 phosphorylation, signaling, breast cancer cell proliferation and migration. Furthermore, re-introduction of phosphor-mimic mutant AR-Y534D, but not wild-type AR reversed Kindlin-2 deficiency-induced inhibition of AR signaling and breast cancer progression. Finally, using a genetic knockout strategy, we show that ablation of Kindlin-2 from mammary tumors in mouse significantly reduced AR Tyr-534 phosphorylation, breast tumor progression and metastasis in vivo. Our results suggest a critical role of Kindlin-2 in promoting breast cancer progression and shed light on the molecular mechanism through which it functions in this process.
Assuntos
Neoplasias da Mama , Proteínas do Citoesqueleto , Proteínas Musculares , Receptores Androgênicos , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Feminino , Humanos , Proteínas de Membrana , Camundongos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas de Neoplasias , Fosforilação , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais , Tirosina/metabolismoRESUMO
To assess the effect of elevated CO2 on the development, fecundity, and population dynamic parameters of L. erysimi, the age-stage, two-sex life table was used to predict the individual fitness and population parameters of three successive generations of L. erysimi in this study. The results show that a significantly longer total pre-adult stage before oviposition (TPOP) was observed in the third generation compared with the first generation of L. erysimi under the 800 µL/L CO2 treatment. The fecundity is significantly lower in the 800 µL/L CO2 treatment than that in the 400 µL/L CO2 treatment in the third generation of L. erysimi, which indicates that elevated CO2 had a negative effect on the individual fitness parameters of L. erysimi. Additionally, the life expectancy (exj) is significantly lower under the 800 µL/L CO2 treatment than that under the 400 µL/L CO2 treatment in the three successive generations. A significantly higher intrinsic rate of increase (r) and finite rate of increase (λ) were found in the second generation compared with those in the first and third generations of L. erysimi under the 800 µL/L CO2 treatment. Moreover, significantly lower r and λ were observed under the 800 µL/L CO2 treatment compared with those under the 400 µL/L and 600 µL/L CO2 treatments in the first generation of L. erysimi, which indicates that elevated CO2 has a short-term effect on the population parameters (r and λ) of L. erysimi. Our experiment can provide the data for the comprehensive prevention and control of L. erysimi in the future with increasing CO2 levels.
RESUMO
This work was to study the guiding value of magnetic resonance imaging (MRI) based on the target region boundary tracking algorithm in lung cancer surgery. In this study, the traditional boundary tracking algorithm was optimized, and the target neighborhood point boundary tracking method was proposed. The iterative method was used to binarize the lung MRI image, which was applied to the MRI images of 50 lung cancer patients in hospital. The patients were divided into two groups as the progression-free survival (PFS) and overall survival (OS) of surgical treatment group (experimental group, n = 25) and nonsurgical treatment group (control group, n = 25). The experimental group received surgical resection, while the control group received systemic chemotherapy. The results showed that the traditional boundary tracking algorithm needed to manually rejudge whether the concave and convex parts of the image were missing. The target boundary tracking algorithm can effectively avoid the leakage of concave and convex parts and accurately locate the target image contour, fast operation, without manual intervention. The PFS time of the experimental group (325 days) was significantly higher than that of the control group (186 days) (P < 0.05). The OS time of the experimental group (697 days) was significantly higher than that of the control group (428 days) (P < 0.05). Fisher exact probability method was used to test the total survival time of patients in the two groups, and the tumor classification and treatment group had significant influence on the OS time (P < 0.05). The target boundary tracking algorithm in this study can effectively locate the contour of the target image, and the operation speed was fast. Surgical resection of lung cancer can improve the PFS and OS of patients.
Assuntos
Algoritmos , Neoplasias Pulmonares , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Imageamento por Ressonância Magnética/métodosRESUMO
Long non-coding RNA (lncRNA) LINC00467 plays a proto-oncogenic role in non-small cell lung cancer. However, its effect and modulatory mechanism in gastric cancer (GC) are unknown. Thereby, we elucidated the mechanism of LINC00467 in GC. LINC00467 level in GC tissues was assessed by bioinformatic analysis, and clinicopathological parameters from GC patients were collected. The levels of LINC00467, integrin subunit beta 3 (ITGB3), proliferating cell nuclear antigen (PCNA), cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase 1 (PARP1) in tissue samples or treated GC cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), or Western blot. The viability, proliferation and apoptosis of GC cells were detected by methyl thiazolyl tetrazolium assay, colony formation assay, and flow cytometry. Levels of LINC00467 and ITGB3 were up-regulated in GC, and highly expressed LINC00467 was positively associated with tumor size, differentiation, N stage, and T stage in GC patients. LINC00467 was enriched in cytoplasm of GC cells, and overexpressed LINC00467 promoted the viability and proliferation as well as levels of ITGB3 and PCNA, while suppressing the apoptosis and levels of cleaved caspase-3 and cleaved PARP1 in GC cells. Besides, the effects of shLINC00467 on inhibiting cell viability, proliferation of GC cells and PCNA level and promoting apoptosis as well as levels of cleaved caspase-3 and cleaved PARP1 were all partially reversed by overexpressed ITGB3. Overexpressed LINC00467 enhanced the viability and proliferation but inhibited apoptosis of GC cells via increasing ITGB3 level.
Assuntos
Apoptose/genética , Integrina beta3/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Idoso , Caspase 3/metabolismo , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Poli(ADP-Ribose) Polimerases/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Longo não Codificante/genética , Carga Tumoral , Regulação para Cima/genéticaRESUMO
PINCH-1 is a cytoplasmic component of the cell-extracellular matrix (ECM) adhesion machine that is frequently overexpressed in cancer. The functions and mechanism of PINCH-1 in cancer, however, remain to be determined. Here, we show that PINCH-1 interacts with myoferlin, a transmembrane protein that is critical for cancer progression. High expression of both PINCH-1 and myoferlin correlates with poor clinical outcome in human breast cancer patients. Ablation of PINCH-1 from breast cancer cells diminished myoferlin level and suppressed breast cancer cell proliferation, migration, and endothelial cell tube formation in vitro and breast tumor growth, angiogenesis and metastasis in vivo. Mechanistically, PINCH-1 controls myoferlin level through its interaction with myoferlin and regulation of its ubiquitination and proteasome-dependent degradation. Functionally, re-expression of PINCH-1, but not that of a myoferlin-binding defectiveΔLIM2 mutant, effectively reversed the inhibition of myoferlin expression and breast cancer progression induced by loss of PINCH-1. Finally, restoration of myoferlin expression was sufficient to reverse PINCH-1-deficiency induced inhibition on breast cancer progression. These results reveal a PINCH-1-myoferlin signaling axis that is critical for breast cancer progression and suggest a new strategy for therapeutic control of breast cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas com Domínio LIM/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Musculares/metabolismo , Metástase Neoplásica , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas com Domínio LIM/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Musculares/genética , Transdução de SinaisRESUMO
Identification of molecular alterations driving breast cancer progression is critical for the development of effective therapy. In this study, we show that the level of α-parvin is elevated in triple-negative breast cancer cells. The depletion of α-parvin from triple-negative breast cancer cells effectively inhibits breast cancer cell growth, migration, and invasion in vitro, and tumor progression and metastasis in vivo. At the molecular level, we identify Ras-GTPase-activing protein SH3-domain-binding protein 2 (G3BP2) as an α-parvin-binding protein. Knockdown of α-parvin promotes G3BP2 interaction with TWIST1, increases ubiquitination and proteasome-dependent degradation of TWIST1, and consequently reduces the cellular level of TWIST1 and its downstream signaling. Importantly, the depletion of G3BP2 reverses the reduction in the level and signaling of TWIST1 and the suppression of breast cancer progression induced by the loss of α-parvin. Furthermore, the re-expression of an α-parvin mutant in which the G3BP2-binding site is ablated, unlike that of wild-type α-parvin, in α-parvin-deficient breast cancer cells, is unable to restore the level and signaling of TWIST1 and promote breast cancer progression. Finally, we show that protein level of α-parvin is highly positively correlated with that of TWIST1 in human triple-negative breast cancer patients. Our studies reveal a novel signaling pathway consisting of α-parvin, G3BP2, and TWIST1 that regulates breast cancer progression and metastasis, and suggest that the activation of this signaling pathway is a key factor for driving the progression and poor clinical outcome of human ER-negative breast cancer.
Assuntos
Neoplasias da Mama/patologia , Proteínas de Transporte/metabolismo , Proteínas dos Microfilamentos/fisiologia , Proteínas Nucleares/genética , Proteína 1 Relacionada a Twist/genética , Proteínas Adaptadoras de Transdução de Sinal , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Células Cultivadas , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Metástase Neoplásica , Ligação Proteica , Proteínas de Ligação a RNA , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: This study aims to compare clinical outcomes using the Perigee versus Elevate anterior devices for the treatment of pelvic organ prolapse (POP). STUDY DESIGN: One hundred and forty-one women with POP stages II to IV were scheduled for either Perigee (n = 91) or Elevate anterior device (n = 50). Preoperative and postoperative assessments included pelvic examination, urodynamic study, and a personal interview about quality of life and urinary symptoms. RESULTS: Despite postoperative point C of Elevate group being significantly deeper than the Perigee group (median: -7.5 versus -6; P < 0.01), the 1-year success rates for two groups were comparable (P > 0.05). Apart from urgency incontinence, women with advanced POP experienced significant resolution of irritating and obstructive symptoms after both procedures (P < 0.05), generating the improvement in postoperative scores of Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) (P < 0.01). On urodynamics, only the residual urine decreased significantly following these two procedures (P < 0.05). Women undergoing Perigee mesh experienced significantly higher visual analogue scale (VAS) scores and vaginal extrusion rates compared with the Elevate anterior procedure (P < 0.05). CONCLUSIONS: With comparable success rates, the Elevate procedure has advantages over the Perigee surgery with lower extrusion rate and postoperative day 1 VAS scores.
Assuntos
Prolapso de Órgão Pélvico/fisiopatologia , Prolapso de Órgão Pélvico/cirurgia , Urodinâmica , Procedimentos Cirúrgicos Urogenitais/instrumentação , Procedimentos Cirúrgicos Urogenitais/métodos , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To compare the efficacy and safety of the modified prepubic tension-free vaginal tape-obturator (PTVT-O) system procedure with the original TVT-O methods. STUDY DESIGN: One hundred and ninety women with urodynamic stress incontinence (USI) were included in this study (93 cases in the TVT-O group and 97 in the PTVT-O group). Clinical assessments before and one year after surgery included urinalyses, 1-h pad tests, urodynamic studies, and a personal interview with the overactive bladder symptom score (OABSS) questionnaire. RESULTS: There were no differences between the two groups in mean age, parity, menopausal status, mean operative time and subjective cure rates (P>0.05), but the efficacy of surgery (cure and improvement) in the PTVT-O group was significantly higher than that in the TVT-O group (P=0.038). Complication rates and visual analog scale (VAS) scores were found to be similar (P>0.05). OABSS decreased significantly after surgery in both groups (P<0.05) although all urodynamic parameters revealed no significant difference after both procedures (P>0.05). CONCLUSION: Our modified procedure is a safe and effective treatment for female USI. It has an advantage over the original TVT-O with better surgical efficacy and comparable postoperative pain, although the follow-up times in this study are different.
Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Urodinâmica , Procedimentos Cirúrgicos Urológicos/instrumentaçãoRESUMO
OBJECTIVE: The aim of this study was to compare the changes in urinary symptoms and urodynamic parameters after administration of tolterodine in women with an overactive bladder (OAB). MATERIALS AND METHODS: Thirty-eight women diagnosed with OAB and treated with tolterodine were reviewed. Urinalysis, pelvic examination, 3-day bladder diary, urodynamic study, and a personal interview to identify urinary symptoms prior to and 3 months after treatment were recorded and interpreted. RESULTS: Most of our patients were menopausal (76.3%; mean age 55.7 years) and multiparous (mean parity 3.3) women. Urinary symptoms such as urinary frequency, urgency, urge incontinence, and nocturia were decreased significantly (p < 0.05). All urodynamic parameters did not change significantly except for the maximum cystometric capacity (p < 0.05), showing a significant increase after 3 months of medication. CONCLUSIONS: Tolterodine, at a recommended dose, improves the symptoms of OAB syndrome without causing urine retention, as proved by the changes of urodynamic parameters.
Assuntos
Compostos Benzidrílicos/administração & dosagem , Cresóis/administração & dosagem , Fenilpropanolamina/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária de Urgência/tratamento farmacológico , Urodinâmica/efeitos dos fármacos , Agentes Urológicos/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Noctúria/tratamento farmacológico , Paridade , Gravidez , Estudos Retrospectivos , Tartarato de Tolterodina , Resultado do TratamentoAssuntos
Abscesso/etiologia , Infecções por Escherichia coli/tratamento farmacológico , Corpos Estranhos/complicações , Distúrbios do Assoalho Pélvico/etiologia , Prolapso de Órgão Pélvico/cirurgia , Tampões de Gaze Cirúrgicos/efeitos adversos , Abscesso/microbiologia , Abscesso/terapia , Idoso , Antibacterianos/uso terapêutico , Feminino , Humanos , Distúrbios do Assoalho Pélvico/terapiaRESUMO
INTRODUCTION: Comparison of female sexual function following anterior and total transvaginal mesh (TVM) surgery has never been reported. AIM: To compare the sexual function after anterior and total TVM repair for the treatment of pelvic organ prolapse (POP). MAIN OUTCOME MEASURES: The short forms of Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7), and the Female Sexual Function Index (FSFI). METHODS: One hundred and sixty-five women with symptomatic POP stages II to IV defined by the POP quantification (POP-Q) staging system underwent TVM procedures at our hospitals. Seventy women were included because they were sexually active and had complete follow-up. All subjects were divided into the anterior group (anterior TVM; N=39) and total group (anterior and posterior TVM; N=31). Preoperative and postoperative assessments included pelvic examination using the POP-Q system, urodynamic study, and a personal interview to evaluate urinary and sexual symptoms with the short forms of UDI-6 and IIQ-7, and the FSFI. RESULTS: There was no difference between the two groups as for age, parity, diabetes, hypertension, concomitant procedures, and success rates for TVM and mid-urethral sling in this study (P>0.05). Regarding the POP-Q analysis, there was a significant improvement at points Aa, Ba, C, Ap, and Bp (P<0.05) in both groups except for total vaginal length (P>0.05). The preoperative scores of UDI-6 and IIQ-7 were significantly higher in the total group (P<0.01), and the UDI-6 and IIQ-7 scores showed significant decreases in both groups postoperatively (P<0.01). After TVM surgery, the score of the dyspareunia domain worsened significantly in both groups (P<0.05), and the deteriorated lubrication domain was noted only in the total group (P=0.042). CONCLUSIONS: TVM procedure creates an effective anatomical restoration of POP, but individual domains of FSFI may worsen. Compared with the anterior group, women of the total group had worse quality of life in term of urinary symptoms preoperatively, and experienced a greater sexual impairment on lubrication following surgery.
Assuntos
Prolapso de Órgão Pélvico/cirurgia , Comportamento Sexual , Disfunções Sexuais Fisiológicas/etiologia , Telas Cirúrgicas/efeitos adversos , Adulto , Dispareunia/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Gravidez , Qualidade de Vida , Inquéritos e Questionários , Urodinâmica , Vagina/cirurgiaRESUMO
OBJECTIVES: We aimed to utilize a simple molecular assay to simultaneously detect both group B Streptococcus (GBS) and virulent ST-17 rectovaginal colonization. We also attempted to estimate the prevalence of maternal GBS and ST-17 carriers and to evaluate their seasonal association. SUBJECTS AND METHODS: We used an optimized multiplex PCR method employing scp-B and ST-17 primers to analyze DNA extracted from rectovaginal swabs of 3,064 cases collected over 3 years. The incidence trends, seasonal variations, and temperature preference were analyzed. RESULTS: The overall prevalence of maternal colonization for GBS and ST-17 clone were 13.25 and 2.48%, respectively. The ST-17 to GBS ratio was 18.72%. The occurrence of ST-17 colonization was significantly associated with seasonal variations with a preference for lower temperatures. CONCLUSIONS: We developed a novel multiplex PCR method suitable for the simultaneous detection of GBS and ST-17 clone. The phenomenon of lower temperature preference for ST-17 clone necessitates further investigation. The epidemiological data for GBS and ST-17 incidence are especially important to establish a public policy for universal GBS screening in the future.
Assuntos
Complicações Infecciosas na Gravidez/microbiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/classificação , Streptococcus agalactiae/isolamento & purificação , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Feminino , Humanos , Reação em Cadeia da Polimerase Multiplex/métodos , Gravidez , Diagnóstico Pré-Natal , Reto/microbiologia , Estações do Ano , Sorotipagem , Streptococcus agalactiae/genética , Taiwan/epidemiologia , Vagina/microbiologiaRESUMO
OBJECTIVE: To identify the factors associated with pelvic organ prolapse (POP) recurrence after transvaginal mesh (TVM) repair. STUDY DESIGN: One hundred and thirteen women with symptomatic POP stage II to IV were scheduled for TVM procedures. All subjects underwent urinalyses and pelvic examination using the POP quantification (POP-Q) staging system before and after surgery. RESULTS: Seven (6.2%) of 113 women reported POP recurrence after a mean follow-up time of 30 months. We performed a univariate analysis of patients' characteristics to identify the predictors of surgical failure after TVM. There was no difference between two groups as to body mass index, POP stage, mesh type, and preoperative urinary symptoms and urodynamic parameters (P>0.05). However, we found that uterine prolapse (P=0.016) and surgical experience (P=0.043) were two significant predictors of surgical failure. Multivariate logistic regression showed similar results. CONCLUSION: Advanced uterine prolapse and lack of surgical experience were two significant predictors of failure following TVM. POP recurrence after mesh repair appears to be unlikely beyond the learning curve.