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BACKGROUND: To study and compare the effects of venoactive drug (VAD) therapy and ovarian vein embolization or resection (OVE or OVR, accordingly) on the levels of vasoactive peptides and cytokines in patients with pelvic venous disorders (PeVDs). METHODS: The study included 70 consecutive female patients with PeVD symptoms, such as chronic pelvic pain (CPP), dyspareunia, dysuria, and vulvar varicosities. Based on the results of clinical examination and duplex ultrasound of the pelvic veins, the patients were allocated to the VAD therapy (n = 38) or OVE/OVR (n = 32). Additionally, the enzyme-linked immunosorbent assay tests were performed to determine levels of calcitonin gene-related peptide (CGRP), substance P (SP), interleukins 6 and 8 (IL-6, IL-8) and monocyte chemotactic protein-1 (MCP-1) after a 2-month course of VAD therapy and at 3 months after OVE/OVR. RESULTS: The VAD therapy was associated with a significant decrease in CPP in 84% of patients with PeVD and isolated lesions of the parametrial veins (PVs) and uterine veins (UVs). VAD had no significant effect on the pelvic venous reflux. No changes in the CGRP, SP, IL-6, IL-8, and MCP-1 levels were detected after treatment. At 3 months after OVE or OVR, all patients with PeVD and combined lesions of the ovarian veins (OVs), PVs and UVs reported almost complete relief of CPP. Along with elimination of reflux in ovarian veins, the disappearance of reflux in PVs and UVs was noted. A decrease in the CGRP and SP levels was observed (0.7 ± 0.1 ng/mL and 0.12 ± 0.02 ng/mL before treatment; 0.5 ± 0.12 ng/mL and 0.09 ± 0.06 ng/mL after treatment, respectively; all P < 0.05). No changes in cytokine levels were revealed. CONCLUSIONS: Treatment with VAD is associated with the CPP relief, but has no significant effect on the CGRP, SP, IL-6, IL-8, and MCP-1 levels. OVE/OVR results in the CPP relief, elimination of the pelvic venous reflux and a significant decrease in the CGRP and SP levels, but does not change cytokine levels.
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Citocinas , Ovario , Dolor Pélvico , Pelvis , Venas , Humanos , Femenino , Persona de Mediana Edad , Adulto , Ovario/irrigación sanguínea , Ovario/efectos de los fármacos , Citocinas/sangre , Venas/diagnóstico por imagen , Venas/efectos de los fármacos , Venas/fisiopatología , Resultado del Tratamiento , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Dolor Pélvico/sangre , Pelvis/irrigación sanguínea , Embolización Terapéutica/efectos adversos , Biomarcadores/sangre , Factores de Tiempo , Insuficiencia Venosa/tratamiento farmacológico , Insuficiencia Venosa/sangre , Insuficiencia Venosa/diagnóstico por imagen , Insuficiencia Venosa/fisiopatología , Anciano , Neuropéptidos/sangre , Ultrasonografía Doppler Dúplex , Sustancia P/sangre , Estudios ProspectivosRESUMEN
INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome. METHODS: literature search using Pub Med with the keywords "bladder pain syndrome", "painful bladder syndrome", "bladder pain", "Interstitial cystitis" AND "cytokines" or "inflammation". This study was except from institutional approval. RESULTS: Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C-C chemokine group (n = 7). CONCLUSIONS: CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C-C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients.
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Cistitis Intersticial , Citocinas , Humanos , Cistitis Intersticial/diagnóstico , Citocinas/sangre , Citocinas/metabolismo , Biomarcadores/sangre , Biomarcadores/orina , Vejiga Urinaria/fisiopatología , Vejiga Urinaria/metabolismo , Femenino , Dolor Pélvico/etiología , Dolor Pélvico/sangre , Dolor Pélvico/diagnósticoRESUMEN
BACKGROUND AND OBJECTIVE: Endometriosis (EM) involves the peripheral nervous system and causes chronic pain. Sensory nerves innervating endometriotic lesions contribute to chronic pain and influence the growth phenotype by releasing neurotrophic factors and interacting with nearby immune cells. Calcitonin gene-related peptide (CGRP), a pain-signaling neurotransmitter, has a significant role. This study examines the effect of Dienogest (DNG), a hormone therapy used for managing EM -related pain, on serum CGRP levels in EM patients. MATERIALS AND METHODS: The Visual Analog Scale (VAS) assessed pain in diagnosed EM. INDIVIDUALS: Serum samples were obtained to measure CGRP concentration. Participants received a 2 mg/day oral dose of DNG for six months as prescribed treatment. Additional serum samples were collected after this period to measure CGRP levels. RESULTS: In the EM group, 6.7%, 33.3%, and 20% had ovarian EM, ovarian plus uterosacral, and ovarian plus bladder, respectively. The EM group showed higher CGRP serum levels than the control group (80.53 ± 16.13 vs. 58.55 ± 6.93, P < 0.0001). Still, after drug administration, CGRP serum levels significantly decreased compared to pre-treatment levels (69.66 ± 11.53 vs. 80.53 ± 16.13, P < 0.05). The EM group showed higher pain compared to the control group (7.93 ± 1.58 vs. 0.13 ± 0.35, P < 0.0001), but after drug administration, pain significantly decreased compared to pre-treatment levels (1.00 ± 2.00 vs. 7.93 ± 1.58, P < 0.05). CONCLUSION: DNG administration reduces pain and serum CGRP levels in EM patients, offering the potential for innovative treatments and tailored options. Understanding neurotransmitter roles and drug effects can aid in discovering more effective modulators for these pathways.
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Péptido Relacionado con Gen de Calcitonina , Endometriosis , Nandrolona , Nandrolona/análogos & derivados , Dolor Pélvico , Humanos , Femenino , Endometriosis/tratamiento farmacológico , Endometriosis/complicaciones , Endometriosis/sangre , Nandrolona/uso terapéutico , Nandrolona/administración & dosificación , Adulto , Péptido Relacionado con Gen de Calcitonina/sangre , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Dolor Pélvico/sangre , Dimensión del Dolor , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/etiología , Adulto JovenRESUMEN
PURPOSE: dentification of bioimpedance and clinical features in young men with chronic pelvic pain inflammatory syndrome (CP/CPPS NIH IIIa) depending on the somatotype. METHOD: s. 150 men of the first period of adulthood from 22 to 35 years old with CP/CPPS NIH IIIa were examined from 2018 to 2022 years. The average age was 31 [28; 34] year. Somatotypes were computed according to Carter and Heath. Body composition was assessed anthropometry and bioimpedance analysis. RESULTS: Ectomorphs had the least clinical, laboratory and instrumental manifestations of CP/CPPS NIH IIIa, the levels of total and free testosterone were the highest. The active cell mass predominated in the component composition of the body. Manifestations in mesomorphs had a moderate degree of severity. Endomorphs had the most severe manifestations of CP/CPPS NIH IIIa, the largest amount of fat mass was noted in the body composition than in men of other somatotypes, the hormonal status was characterized by the lowest levels of free and total testosterone, and the highest level of estradiol. DISCUSSION: Based on the literature data and our own results, it can be assumed that the identified changes in the body component composition and hormonal status of men contribute to the maintenance of chronic inflammation in the prostate, organ ischemia, impaired intracranial metabolism, recurrent course of CP/CPPS NIH IIIa, which significantly reduces the patients quality of life and increases the risk of prostate inflammation with age. CONCLUSION: Determining the somatotype and conducting a component analysis of body composition allows patients to be divided into groups according to the severity of manifestations of CP/CPPS NIH IIIa. The revealed patterns allow us to classify male endomorphs into the group with the most severe manifestations of CP/CPPS NIH IIIa.
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Composición Corporal , Dolor Pélvico , Prostatitis , Somatotipos , Humanos , Masculino , Prostatitis/metabolismo , Prostatitis/sangre , Prostatitis/complicaciones , Prostatitis/patología , Adulto , Dolor Pélvico/sangre , Dolor Pélvico/etiología , Dolor Pélvico/metabolismo , Adulto Joven , Testosterona/sangre , Dolor Crónico/sangre , Dolor Crónico/etiologíaRESUMEN
BACKGROUND: Noninvasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biologic pathways underlying endometriosis-associated pain and symptom progression. OBJECTIVE: To use plasma proteins in relation to the persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform. STUDY DESIGN: We conducted a prospective analysis including 142 participants with laparoscopically-confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1305 plasma protein levels, including markers for immunity, angiogenesis, and inflammation, using SomaScan. Worsening or persistent postsurgical pelvic pain was defined as having newly developed, persistent (ie, stable), or worsening severity, frequency, or persistent life interference of dysmenorrhea or acyclic pelvic pain at 1-year postsurgery compared with presurgery. We calculated odds ratios and 95% confidence intervals using logistic regression adjusted for age, body mass index, fasting status, and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions. RESULTS: The median age at blood draw was 17 years (interquartile range, 15-19 years), and most participants were White (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year postsurgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, whereas pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain 1-year postsurgery (nominal P<.05). Compared with those with improved pelvic pain 1-year postsurgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (odds ratio, 2.98 [95% confidence interval, 1.44-6.19]) and CD47 (odds ratio, 2.68 [95% confidence interval, 1.28-5.61]), but lower levels of Sonic Hedgehog protein (odds ratio, 0.55 [95% confidence interval, 0.36-0.84]) in presurgical blood. Pathways related to cell migration were up-regulated, and pathways related to angiogenesis were down-regulated in those with worsening or persistent postsurgical pelvic pain compared with those with improved pain. When we examined the change in protein levels from presurgery to postsurgery and its subsequent risk of worsening or persistent postsurgical pain at 1-year follow-up, we observed increasing levels of Sonic Hedgehog protein from presurgery to postsurgery was associated with a 4-fold increase in the risk of postsurgical pain (odds ratio [quartile 4 vs 1], 3.86 [1.04-14.33]). CONCLUSION: Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain postsurgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis.
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Biomarcadores , Proteínas Sanguíneas , Endometriosis , Dolor Pélvico , Humanos , Femenino , Endometriosis/cirugía , Endometriosis/sangre , Endometriosis/complicaciones , Adolescente , Dolor Pélvico/sangre , Dolor Pélvico/cirugía , Adulto Joven , Biomarcadores/sangre , Estudios Prospectivos , Adulto , Dolor Postoperatorio/sangre , Estudios Longitudinales , Laparoscopía , Dismenorrea/sangre , Dismenorrea/cirugía , Dismenorrea/etiología , ProteómicaRESUMEN
Endometriosis is a common, chronic inflammatory condition, thought to have a higher incidence in symptomatic women, yet, commonly associated symptoms do not always correlate with the presence or severity of disease and diagnosis requires surgery. We prospectively collected data and assessed symptomology and NMR spectroscopy-based metabolomics of 102 women undergoing laparoscopic sterilisation at a tertiary referral centre in a cross-sectional study. Twelve women were incidentally diagnosed with endometriosis (11.7%). According to the pre-operative questionnaire, presence and absence of many symptoms usually attributed to endometriosis were declared at similar frequencies in women with or without endometriosis. Women with endometriosis reported apparently more persistent heavy periods (50% vs 18.9%), prolonged periods (25% versus 7.8%) and problems conceiving (27.3% versus 9%) than those without endometriosis. NMR could not discern any distinguishable differences in the serum metabolome between those with and without endometriosis. Our paper highlights the complex symptomology experienced by women, regardless of a surgical diagnosis of endometriosis. Previous literature and the current study failed to identify clear, distinguishable symptoms or biomarkers pertinent to surgically confirmed endometriosis in the general population. Therefore, development of effective, non-invasive tests for identifying this heterogenous benign condition, endometriosis, is likely to be challenging.
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Endometriosis/sangre , Endometriosis/diagnóstico , Laparoscopía/métodos , Espectroscopía de Resonancia Magnética/métodos , Metabolómica/métodos , Esterilización Reproductiva/métodos , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Dolor Pélvico/sangre , Dolor Pélvico/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Mechanisms of the brain-related comorbidities in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still largely unknown, although CP/CPPS is one of the major urological problems in middle-aged men, while these neuropsychological incapacities considerably diminish life quality. The objectives of this study were to assess behavioral patterns in rats with CP/CPPS and to determine whether these patterns depend on alterations in the brain oxidative stress, corticosterone, and hippocampal parvalbumin-positive (PV+) interneurons. Adult male Wistar albino rats from CP/CPPS (intraprostatic injection of 3% λ-carrageenan, day 0) and sham (0.9% NaCl) groups were subjected to pain and anxiety-like behavior tests (days 2, 3, and 7). Afterwards, rats were sacrificed and biochemical and immunohistochemical analyses were performed. Scrotal allodynia and prostatitis were proven in CP/CPPS, but not in sham rats. Ethological tests (open field, elevated plus maze, and light/dark tests) revealed significantly increased anxiety-like behavior in rats with CP/CPPS comparing to their sham-operated mates starting from day 3, and there were significant intercorrelations among parameters of these tests. Increased oxidative stress in the hippocampus, thalamus, and cerebral cortex, as well as increased serum corticosterone levels and decreased number of hippocampal PV+ neurons, was shown in CP/CPPS rats, compared to sham rats. Increased anxiety-like behavior in CP/CPPS rats was significantly correlated with these brain biochemical and hippocampal immunohistochemical alterations. Therefore, the potential mechanisms of observed behavioral alterations in CP/CPPS rats could be the result of an interplay between increased brain oxidative stress, elevated serum corticosterone level, and loss of hippocampal PV+ interneurons.
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Ansiedad/sangre , Conducta Animal , Encéfalo/patología , Corticosterona/sangre , Interneuronas/metabolismo , Estrés Oxidativo , Dolor Pélvico/sangre , Prostatitis/sangre , Animales , Dolor Crónico/sangre , Dolor Crónico/fisiopatología , Prueba de Laberinto Elevado , Hipocampo , Masculino , Actividad Motora , Umbral del Dolor , Parvalbúminas/metabolismo , Próstata/patología , Prostatitis/fisiopatología , Ratas Wistar , SíndromeRESUMEN
OBJECTIVES: To determine the effect of neurogenic acupoint dry cupping therapy on high sensitive C-reactive protein (hs-CRP) level, pain perception & intensity, and life impact of pelvic pain in women with chronic pelvic pain (CPP), with regard to the biological and neurophysiological impacts of dry cupping on acupoint. METHODS: Thirty women with CPP were randomly divided into two equal groups; the study group received dry cupping on neurogenic acupoints plus lifestyle modifications for 8 weeks (n=15), while the control group received only lifestyle modifications for 8 weeks (n=15). Women were assessed pre- and post-rehabilitation program with the hs-CRP blood test, the short-form McGill Pain Questionnaire (SF-MPQ), and the pelvic pain impact questionnaire (PPIQ). RESULTS: Comparing both groups post-treatment revealed that there were significant reductions in levels of hs-CRP, and scores of SF-MPQ & PPIQ (p<0.05) in the study group compared with the control group. Also, there were significant positive correlations between hs-CRP and both SF-MPQ "Visual Analogue Scale (VAS), Present Pain Intensity (PPI) index & Pain Rating Index (PRI)" and PPIQ (p<0.05). CONCLUSION: Neurogenic acupoint cupping therapy had significantly improving effects on the degree of inflammation, pain perception & intensity, and life impact of pelvic pain in women with CPP.
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Puntos de Acupuntura , Proteína C-Reactiva/metabolismo , Dolor Crónico/sangre , Ventosaterapia/métodos , Percepción del Dolor/fisiología , Dolor Pélvico/sangre , Adulto , Dolor Crónico/psicología , Dolor Crónico/terapia , Ventosaterapia/psicología , Femenino , Humanos , Dimensión del Dolor/métodos , Dimensión del Dolor/psicología , Dolor Pélvico/psicología , Dolor Pélvico/terapia , Estudios Prospectivos , Conducta de Reducción del Riesgo , Resultado del TratamientoRESUMEN
Altered immune mechanisms are implicated in the pathogenesis of endometriosis. CTLA-4 is a membrane receptor that favors the anergic state of lymphocytes, which may disrupt the immune system response in the endometriotic environment. In this study, we examined the expression of CTLA-4 on T and B cells by flow cytometry and its levels in blood serum and peritoneal fluid by ELISA. Levels of CTLA-4+ T cells were significantly higher in patients with more advanced endometriosis than in those with less advanced disease. Additionally, the negative correlation of CTLA-4+ T lymphocytes and the percentage of NK and NKT-like cells in women with endometriosis and infertility may indicate a different etiopathogenesis of endometriosis accompanying infertility. Our findings shed light on the potential of CTLA-4 in developing new diagnostic and therapeutic approaches in endometriosis management.
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Antígeno CTLA-4/metabolismo , Endometriosis/metabolismo , Infertilidad/metabolismo , Inflamación/metabolismo , Adulto , Antígenos CD19/metabolismo , Líquido Ascítico/metabolismo , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Antígeno CTLA-4/sangre , Estudios de Casos y Controles , Enfermedad Crónica , Endometriosis/sangre , Endometriosis/inmunología , Femenino , Humanos , Infertilidad/sangre , Infertilidad/inmunología , Inflamación/sangre , Inflamación/inmunología , Persona de Mediana Edad , Dolor Pélvico/sangre , Dolor Pélvico/complicaciones , Dolor Pélvico/inmunología , Solubilidad , Linfocitos T/inmunología , Adulto JovenRESUMEN
OBJECTIVE: To analyze the predictive value of neutrophils, lymphocytes, platelets, neutrophils to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR) in identifying the occurrence of post-embolization syndrome (PES) after uterine artery embolization (UAE). METHODS: We conducted a retrospective observational study in a single tertiary care center located in New York City during period of November 2014 - December 2018, for patients who underwent UAE. PES was defined as the occurrence of pelvic pain, nausea or fever within one week after the procedure. RESULTS: We enrolled 62 patients: 12 of them had PES and 50 served as controls. Platelets were statistically significantly higher in patients with PES (p=0.036). Specifically, a platelet count greater than 336×103/uL was identified as cut-off with a specificity of 91.8 %, a sensitivity of 33.3 %, a positive predictive value of 46 % and a negative predictive value of 85 %. The area under the curve (AUC) was 0.721 (CI 0.536-0.907). CONCLUSION: Patients with a preprocedural platelet count less than 336×103/uL were less likely to have PES. If confirmed by larger studies, the platelet count could be incorporated into patient counseling and preoperative algorithms to identify the ideal UAE candidates.
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Fiebre/sangre , Náusea/sangre , Dolor Pélvico/sangre , Recuento de Plaquetas , Embolización de la Arteria Uterina/efectos adversos , Adulto , Algoritmos , Área Bajo la Curva , Femenino , Fiebre/etiología , Humanos , Recuento de Leucocitos , Recuento de Linfocitos , Persona de Mediana Edad , Náusea/etiología , Neutrófilos/citología , Dolor Pélvico/etiología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , SíndromeRESUMEN
Chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS) is a clinical tricky problem due to its enigmatic etiology, low cure rate, and high recurrence rate. The research on its pathogenesis has never stopped. In this experimental autoimmune prostatitis (EAP) model, male C57BL/6 mice were subcutaneously immunized with prostate extracts in an adequate adjuvant. For mice in the antibody intervention group, anti-T2 polyclonal antibodies were intraperitoneally injected during the induction of EAP. Animals were periodically monitored for pelvic pain. Hematoxylin and eosin staining was used to assess prostate inflammation. Tumor necrosis factor-α (TNF-α) levels in serum were measured by ELISA kits. The immunized animals developed prostatitis as a consequence of the immune response against prostate antigens. Pelvic pain thresholds were gradually decreased and TNF-α expression significantly increased. T2 plays an important role in the disease since polyclonal antibodies to T2 greatly ameliorated symptoms in animals induced for EAP. T2 peptide may represent the major autoantigen epitope in EAP, which could serve for a better understanding of the etiology of CP/CPPS.
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Autoantígenos/sangre , Enfermedades Autoinmunes/sangre , Epítopos/sangre , Dolor Pélvico/sangre , Fragmentos de Péptidos/antagonistas & inhibidores , Prostatitis/sangre , Secuencia de Aminoácidos , Animales , Autoantígenos/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/prevención & control , Epítopos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Dolor Pélvico/inmunología , Dolor Pélvico/prevención & control , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/inmunología , Prostatitis/inmunología , Prostatitis/prevención & control , ConejosRESUMEN
OBJECTIVE: Genital endometriosis (GE) is a widespread gynecological disease which requires its further pathogenesis investigation and search for new effective treatments. The known data of oxytocin receptor presence in endometrioid heterotopy smooth muscle cells give some grounds to assume oxytocin participation in the pathogenesis of endometriosis. The present study objective was to evaluate oxytocin level in peripheral blood (PB) in patients with endometriosis associated pain syndrome and to estimate the efficacy of oxytocin receptor inhibitors (IOXTR) administration based on animal endometriosis model. MATERIALS AND METHODS: The basic group comprised 61 patients with endometriosis associated pain syndrome, while 21 patients formed the control group. VAS, MPQ, and BBS objective tests were applied for pain syndrome evaluation. Oxytocin level in PB was measured by immunoenzyme method. After confirmation of endometriosis experimental model formation in rats and further randomization, a daily IOXTR intra-abdominal injection was performed in a dose of 0.35 mg/kg/24 h in the basic group (n = 12) or saline solution administration in the control (n = 12). On the final stage, endometrioid heterotopy size measuring was performed along with histological examination. RESULTS: Oxytocin level in PB was authentically higher in patients with GE compared to the control: 51.45 (35.54-62.76) pg/mL and 27.64 (23.23-34.12) pg/mL, respectively (p<.001). Positive correlation between oxytocin PB level and pain syndrome expression was established in patients with GE: VAS (r = 0.76; p<.001), MPQ (r = 0.52; p<.001), and BBS (r = 0.57; p<.001). Based on the experimental disease model authentical decrease of endometrioid heterotopy average area was observed after IOXTR therapy compared to the control (7.3 ± 1.8 mm2 and 22.2 ± 1.2 mm2, respectively, p<.05). CONCLUSIONS: The obtained results confirm the oxytocin role in the pathogenesis of endometrioid associated pain syndrome. The high efficacy of IOXTR administration based on animal model of surgically induced endometriosis allows viewing this method as a perspective therapy.
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Endometriosis/tratamiento farmacológico , Enfermedades Peritoneales/tratamiento farmacológico , Receptores de Oxitocina/antagonistas & inhibidores , Vasotocina/análogos & derivados , Adolescente , Adulto , Animales , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Endometriosis/sangre , Endometriosis/complicaciones , Endometriosis/patología , Femenino , Humanos , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/tendencias , Oxitocina/análogos & derivados , Oxitocina/sangre , Dolor Pélvico/sangre , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Dolor Pélvico/patología , Enfermedades Peritoneales/sangre , Enfermedades Peritoneales/complicaciones , Enfermedades Peritoneales/patología , Ratas , Ratas Wistar , Síndrome , Vasotocina/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Endometriosis is a long-standing progressive disease that affects women of reproductive age. Macrophage migration inhibitory factor (MIF) is one of non-invasive blood biomarker that was detected in sera of endometriotic patients. The present study aimed to determine the accuracy of serum MIF in diagnosing endometriosis in women with infertility and chronic pelvic pain, and correlate its level to the stage of the disease. METHODS: Observational case-control study conducted at Fayoum University hospital from March 2016 till September 2018. Three hundred women candidate for diagnostic laparoscopy for either infertility or gynecologic chronic pelvic pain were included. The study group included patients with symptoms suggestive of endometriosis or chocolate cyst by ultrasound and proved by laparoscopy and histopathology. The control group included other causes of infertility or pelvic pain. All patients undergone either diagnostic or operative laparoscopy, and before laparoscopy blood sampling for quantitative measurement of macrophage migration inhibitory factor (MIF) protein in serum by ELISA technique. RESULTS: The level of serum MIF was significantly higher in endometriosis group compared to control group (1.75 ± 1.48 pg/ml and 0.51 ± 0.45 pg/ ml, respectively, P = < 0.001), with a progressive increase with advancing stage (stage I, 1.3 ± 1.03 pg/ml, stage II, 1.7 ± 1.57 pg/ml, stage III, 2.1 ± 1.19 pg/ml and in stage IV, 3.2 ± 2.6 pg/ml). Moreover, in patients presented with pain and infertile patients showed significantly higher levels of serum MIF (1.92 ± 1.13 vs 1.21 ± 1.17 and 1.82 ± 1.13 vs 1.32 ± 0.91 respectively with p-value < 0.001). ROC curve of serum MIF with a cut off value of 0.85 pg/ml or more achieves a sensitivity of 80.6%, specificity of 83.3%, positive predictive value of 82.9% and negative predictive value of 81.2%. CONCLUSION: Serum MIF might be a promising marker not only for noninvasive diagnosis of endometriosis but as a target for detecting severity as well.
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Endometriosis/diagnóstico , Endometrio/diagnóstico por imagen , Infertilidad Femenina/complicaciones , Factores Inhibidores de la Migración de Macrófagos/sangre , Dolor Pélvico/etiología , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Endometriosis/sangre , Endometriosis/inmunología , Endometrio/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Infertilidad Femenina/sangre , Infertilidad Femenina/inmunología , Laparoscopía , Dolor Pélvico/sangre , Dolor Pélvico/inmunologíaRESUMEN
Some chronic pain conditions and comorbidities suppress the hypothalamic-pituitary-adrenal (HPA) axis and response to dynamic testing. We measured HPA axis responses to corticotropin-releasing hormone (CRH) administration in relation to chronic pelvic pain and endometriosis. In a cross-sectional study of women (n = 54) with endometriosis-associated chronic pelvic pain (n = 22), chronic pelvic pain alone (n = 12), or healthy volunteers (n = 20), adrenocorticotropic-releasing hormone (ACTH) and cortisol levels were measured at 0, 15, 30, and 45 min after intravenous ovine CRH administration. ACTH and cortisol delta (peak-baseline) and area under the curve (AUC) were compared by study group and assessed for association with race and menstrual and non-menstrual pain severity. HPA axis responses did not differ among the racially diverse groups or in those with pain compared with healthy volunteers. However, when stratified by race, ACTH delta (129.9 ± 130.7 vs. 52.5 ± 66.0 pg/mL; p = 0.003), ACTH AUC (4813 ± 4707 vs. 2290 ± 2900 min*pg/mL; p = 0.013), and cortisol delta (26.3 ± 21.5 vs. 13.2 ± 9.7 µg/mL; p = 0.005) were significantly higher in black (n = 10) than predominately white (non-black) subjects (n = 44; 39/44 white). In analyses among primarily white (non-black) women, greater menstrual pain severity was associated with blunted ACTH delta (p = 0.015) and cortisol delta (p = 0.023), and greater non-menstrual pain severity with blunted cortisol delta (p = 0.017). Neuroendocrine abnormalities in women with chronic pelvic pain may differ by pain manifestations and may vary by race. The higher HPA axis response in black women merits investigation in pelvic pain studies stratified by race. In white (non-black) women experiencing pain, a blunted response was related to pain severity suggesting pain affects women independently of endometriosis lesions.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Dolor Crónico/sangre , Endometriosis/sangre , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/fisiopatología , Dolor Pélvico/sangre , Sistema Hipófiso-Suprarrenal/fisiopatología , Adulto , Dolor Crónico/etiología , Dolor Crónico/fisiopatología , Hormona Liberadora de Corticotropina/farmacología , Estudios Transversales , Endometriosis/complicaciones , Endometriosis/fisiopatología , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Persona de Mediana Edad , Dolor Pélvico/etiología , Dolor Pélvico/fisiopatología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Adulto JovenRESUMEN
The aim of this study was to evaluate whether balneotherapy might be effective in patients with chronic pelvic pain (CPP) in the short term. This was an open and prospective pilot study. The balneotherapy programme was performed in a spa resort located in Wando Island, Republic of Korea from August 26 2018 to September 1 2018. It consisted of 10 heated seawater baths (38 °C, 20 minutes) and 10 mud-pack applications (40 °C, 10 minutes) for five days. Sixteen patients were enrolled. Upon analysing responses from a patient questionnaire, we found improvement in parameters such as pain, bladder irrigation symptoms and quality of life after balneotherapy. Inflammatory marker IL-1 and TNF-α was significantly decreased after treatment compared to baseline. There were no adverse events during treatment. Our data suggest that five-day balneotherapy can be beneficial for patients with CPP in the short term.Impact statementWhat is already known on this subject? The majority of articles in the field of balneotherapy discuss the treatment of rheumatic or dermatological disease. However, data on the effectiveness of balneotherapy for chronic pelvic pain are very limited.What the results of this study add? Our study suggests that balneotherapy can be beneficial for patients with CPP in the short-term. The duration of balneotherapy was five days, which is shorter than that of the European studies. Intuitively, it may be doubtful whether short-term therapy has any practical effect. As most people living in Korea have a vacation period of about one week each in summer and winter, the choice of a five-day programme in our study reflects the reality of vacation schedules.What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to demonstrate the persistence of these benefits on the long term, as well as their existence in appropriate control group and different duration of treatment.
Asunto(s)
Balneología/métodos , Peloterapia/métodos , Dolor Pélvico , Calidad de Vida , Irrigación Terapéutica/métodos , Dolor Crónico , Duración de la Terapia , Femenino , Humanos , Interleucina-1/sangre , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Dolor Pélvico/sangre , Dolor Pélvico/etiología , Dolor Pélvico/psicología , Dolor Pélvico/terapia , Proyectos Piloto , Estudios Prospectivos , República de Corea/epidemiología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: Vaginal diazepam is frequently used to treat pelvic floor tension myalgia and pelvic pain despite limited knowledge of systemic absorption. AIM: To determine the pharmacokinetic and adverse event profile of diazepam vaginal suppositories. METHODS: We used a prospective pharmacokinetic design with repeated assessments of diazepam levels. Eight healthy volunteers were administered a 10-mg compounded vaginal diazepam suppository in the outpatient gynecologic clinic. Serum samples were collected at 0, 45, 90, 120, and 180 minutes; 8, 24, and 72 hours; and 1 week following administration of a 10-mg vaginal suppository. The occurrence of adverse events was assessed using the alternate step and tandem walk tests, the Brief Confusion Assessment Method, and numerical ratings. Plasma concentrations of diazepam and active long-acting metabolites were measured. Pharmacokinetic parameters were calculated by standard noncompartmental methods. RESULTS: The mean peak diazepam concentration (Cmax) of 31.0 ng/mL was detected at a mean time (Tmax) of 3.1 hours after suppository placement. The bioavailability was found to be 70.5%, and the mean terminal elimination half-life was 82 hours. The plasma levels of temazepam and nordiazepam peaked at 0.8 ng/mL at 29 hours and 6.4 ng/mL at 132 hours, respectively. Fatigue was reported by 3 of 8 participants. CLINICAL IMPLICATIONS: Serum plasma concentrations of vaginally administered diazepam are low; however the half-life is prolonged. STRENGTHS & LIMITATIONS: Strengths include use of inclusion and exclusion criteria aimed at mitigating clinical factors that could adversely impact diazepam absorption and metabolism, and the use of an ultrasensitive LC-MS/MS assay. Limitations included the lack of addressing the efficacy of vaginal diazepam in lieu of performing a pure pharmacokinetic study with healthy participants. CONCLUSION: Vaginal administration of diazepam results in lower peak serum plasma concentration, longer time to peak concentration, and lower bioavailability than standard oral use. Providers should be aware that with diazepam's long half-life, accumulating levels would occur with chronic daily doses, and steady-state levels would not be reached for up to 1 week. This profile would favor intermittent use to allow participation in physical therapy and intimacy. Larish AM, Dickson RR, Kudgus RA, et al. Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile. J Sex Med 2019;16;763-766.
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Diazepam/farmacocinética , Relajantes Musculares Centrales/farmacocinética , Trastornos del Suelo Pélvico/tratamiento farmacológico , Administración Intravaginal , Administración Oral , Adulto , Cromatografía Liquida , Dolor Crónico/sangre , Dolor Crónico/tratamiento farmacológico , Diazepam/administración & dosificación , Dispareunia/sangre , Dispareunia/tratamiento farmacológico , Femenino , Semivida , Voluntarios Sanos , Humanos , Masculino , Relajantes Musculares Centrales/administración & dosificación , Mialgia/sangre , Mialgia/tratamiento farmacológico , Diafragma Pélvico , Trastornos del Suelo Pélvico/sangre , Dolor Pélvico/sangre , Dolor Pélvico/tratamiento farmacológico , Estudios Prospectivos , Supositorios , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
We investigated the clinical characteristics of patients with varicocele according to the presence or absence of scrotal pain. We retrospectively reviewed the records of patients who underwent varicocelectomy. The age, body mass index, grade, laterality of varicocele, testicular volume difference, time to hospital visit, serum testosterone level and semen parameters were evaluated. A total of 954 patients were included. The painful group had lower mean age, lower BMI, higher grade of varicocele, smaller testicular volume difference and shorter time to hospital visit than the painless group. In addition, the median serum total testosterone level and total sperm count, concentration and motility were higher in the painful group than in the painless group. In multivariate analysis, there were significant differences between the two groups in age, grade of varicocele, testis volume difference, time to hospital visit, total sperm count and concentration. Patients with painful varicocele visited hospital earlier because of the pain and tended to start treatment sooner. They were also younger, had smaller testis atrophy and had higher sperm concentration, even though they had a higher grade of varicocele than patients without pain. Although scrotal pain in varicocele patients is difficult to treat, it leads to early diagnosis and treatment.
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Dolor Pélvico/diagnóstico , Motilidad Espermática/fisiología , Testosterona/sangre , Varicocele/complicaciones , Adolescente , Adulto , Índice de Masa Corporal , Humanos , Masculino , Dimensión del Dolor , Dolor Pélvico/sangre , Dolor Pélvico/etiología , Estudios Retrospectivos , Análisis de Semen , Recuento de Espermatozoides , Evaluación de Síntomas , Varicocele/sangre , Adulto JovenRESUMEN
OBJECTIVE: The aim of the study was to assess the serum levels of the following biomarkers in women with endometriosis-associated pelvic pain before and after six months of using the etonogestrel (ENG) contraceptive implant or the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS): cancer antigen (CA)-125, cluster of differentiation (CD) 23 and endometrial nerve fibre density. METHODS: The study was conducted at the Department of Obstetrics and Gynaecology, University of Campinas Medical School, Brazil. A total of 103 women with endometriosis-associated pain diagnosed by surgery, transvaginal ultrasound and/or magnetic resonance imaging were included. Endometrial nerve fibre density and serum levels of CA-125 and soluble CD23 were assessed before and after six months of using the allocated method and were correlated to 10 cm visual analogue scale (VAS) scores for non-cyclical pelvic pain and dysmenorrhoea. RESULTS: Both contraceptive methods significantly reduced concentrations of serum soluble CD23 and endometrial nerve fibre density (p < .001); however, CA-125 was significantly reduced only among users of the ENG implant (p < .05). No correlation was observed between reduction of biomarkers and improvement of VAS pain and dysmenorrhoea scores. No differences were observed between the ENG implant and the LNG-IUS. CONCLUSION: Both progestin-only contraceptives significantly reduced two out of the three biomarkers evaluated. These two biomarkers could, therefore, be used as surrogate markers to follow up medical treatment of endometriosis-associated pain.
Asunto(s)
Anticonceptivos Femeninos/administración & dosificación , Desogestrel/administración & dosificación , Endometriosis/sangre , Levonorgestrel/administración & dosificación , Dolor Pélvico/sangre , Adulto , Biomarcadores/sangre , Brasil , Antígeno Ca-125/sangre , Implantes de Medicamentos/administración & dosificación , Endometriosis/complicaciones , Endometriosis/tratamiento farmacológico , Endometrio/inervación , Femenino , Humanos , Dispositivos Intrauterinos Medicados , Fibras Nerviosas/patología , Dolor Pélvico/etiología , Receptores de IgE/sangre , Resultado del TratamientoRESUMEN
PURPOSE: Immune mechanisms have been hypothesized to contribute to the development of CP/CPPS. In this study, we investigated the differential expression of immune factors between patients with CP/CPPS and healthy volunteers. METHODS: This study was registered in Australian New Zealand Clinical Trials Registry. Healthy volunteers and patients with CP/CPPS were enrolled in this study. The inclusion criteria for patients were below: (1) aged 18-45 years old; (2) prostatitis-related syndrome longer than 3 months; (3) normal routine urine culture and negative bacterial culture in prostatic fluid. Patients were further classified into two groups: types IIIA and IIIB CP/CPPS according to the results of EPS routine test. Serum immune markers include IgA, IgM, IgG, CD4+ and CD8+. RESULTS: There are total 23 CP/CPPS patients, including 12 type IIIB and 11 type IIIA. Relatively, there are 26 healthy volunteers. The serum levels of IgG were higher in CP/CPPS patients compared to healthy volunteers (1141.2 ± 204.3 vs 1031.9 ± 173.7 mg/L, p = 0.045), while the serum levels of CD8+ were lower in CP/CPPS patients compared to healthy volunteers (492.8 ± 185.6 vs 640.0 ± 246.8 cells/µL, p = 0.021). Furthermore, serum levels of IgG were higher in patients with IIIA CP/CPPS compared to those with IIIB (1244.3 ± 151.6 vs 1054.3 ± 209.3 mg/L, p = 0.023). CONCLUSIONS: Differential levels of IgG and CD8+ between CPPS patients and healthy volunteers suggest a contributing role of immune mechanisms to the development of CP/CPPS; and IgG may play an important role in inflammatory CPPS. Clinical Study registration number ACTRN12613000792729.
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Recuento de Linfocito CD4 , Linfocitos T CD8-positivos , Dolor Crónico/sangre , Inmunoglobulinas/sangre , Dolor Pélvico/sangre , Prostatitis/sangre , Adulto , Estudios de Casos y Controles , Enfermedad Crónica , Dolor Crónico/clasificación , Voluntarios Sanos , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Dolor Pélvico/clasificación , Prostatitis/clasificación , Síndrome , Adulto JovenRESUMEN
A mouse model was developed to simulate the clinical features of chronic prostatitis/chronic pelvic pain syndrome using peptide (T2 ). Forty C57BL/6 mice were divided into four groups of 10 mice each, averagely and randomly. T2 plus aluminium hydroxide adjuvant group was given subcutaneous injection with the emulsion mixture of T2 and aluminium hydroxide adjuvant, the T2 group with T2 , the aluminium hydroxide adjuvant group with aluminium hydroxide adjuvant and the normal control group with 0.9/% NaCl solution. Haematoxylin andeosin staining was used to observe the inflammation of the prostate. Plasma levels of TNF-α and CRP were detected by ELISA kit. The expression of IL-1ßin the prostate was investigated by immunohistochemistry. The statistical differences between the groups were compared by t test. Histopathological analyses demonstrated that prostate lesions were most severe in the group immunised with T2 plus aluminium hydroxide adjuvant. Plasma levels of TNF-α and CRP were statistically elevated compared with control groups. The expression levels of IL-1ß in the prostate were more obvious than control groups. T2 in aluminium hydroxide adjuvant subcutaneous injection could successfully set up experimental autoimmune prostatitis in C57BL/6 mice. This murine model would be greatly beneficial to further comprehend the aetiology, pathogenesis and explicit treatment of CP/CPPS.