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1.
J Turk Ger Gynecol Assoc ; 25(2): 66-73, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867687

RESUMO

Objective: Gliomatosis peritonei (GP) is a rare entity characterized by multiple mature glial tissue implants in association with ovarian teratomas in the peritoneum and omentum. To date, only 100 cases have been published. Not much is known about the origin, clinicopathological profile or prognosis of GP. SOX2 and OCT4 are recently recognized markers of embryonic stem cell differentiation. Here, the role of SOX2 and OCT4 in the pathogenesis of 11 cases of GP are reported and clinicopathological factors are described. Material and Methods: This was a retrospective study of six years duration (2017-2022). All the cases of GP were retrieved from archives, the diagnosis was confirmed and clinicopathological factors were noted. Immunohistochemical (IHC) investigation for glial fibrillary acid protein (GFAP) and S100 was noted wherever available. IHC for SOX2 and OCT4 was performed using an avidin-biotin technique. Results: There were 11 cases of GP identified. The median age was 29 years and 1/11 cases had nodal gliomatosis as well. There were eight cases of immature teratoma and three cases of mature cystic teratoma. SOX2 was positive in all foci of GP, while OCT4 was negative. These foci were also positive for GFAP and S100. Conclusion: A possibility of GP should be considered as a differential, clinically and radiologically, in cases of omental nodularity. Adequate sampling at the time of surgery is essential to rule out metastasis or growing teratoma syndrome. SOX2, a stem cell marker inducing neural differentiation, may play a crucial role in the development of GP in association with other transcription factors.

2.
J Hum Reprod Sci ; 17(1): 50-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665608

RESUMO

Background: Polycystic ovary syndrome (PCOS) women are at risk of developing diabetes, cardiovascular disease and metabolic syndrome (MetS) due to insulin resistance (IR) and hyperandrogenism (HA). Both visceral adiposity index (VAI) and lipid accumulation product (LAP) are simple outpatient department-based metric tools that have been introduced to screen PCOS women who are metabolically unhealthy and are at risk of development of MetS. Aims: The aim of the study was to evaluate VAI and LAP in women with PCOS and to correlate them with metabolic and endocrine markers. The study also assessed these parameters amongst different PCOS phenotypes and determined their usefulness to define metabolically healthy PCOS (MH-PCOS) and metabolically unhealthy PCOS (MU-PCOS). Settings and Design: The design of the study was a cross-sectional study. Materials and Methods: Two hundred PCOS women were included in the study, and all the clinical, anthropometric, hormonal, biochemical and metabolic markers were assessed. The cohort was divided into MH-PCOS and MU-PCOS by the modified National Cholesterol Education Programme criteria. VAI and LAP were calculated and correlated with clinical, endocrine and metabolic parameters. Statistical Analysis Used: Univariate and multivariate logistic regression analysis was used to study the independent role of VAI and LAP to predict MetS. Adjusted and unadjusted odds ratios were calculated. Receiver-operating characteristic (ROC) analysis was done to define cut-offs in Asian Indian women. Results: VAI and LAP had good ability to correctly discriminate MU-PCOS from MH-PCOS (area under the curve [AUC] [95% confidence interval (CI)]: 0.89 [0.82-0.95]) and (AUC [95% CI [0.81-0.92] =0.86) using ROC, respectively. The sensitivity of VAI and LAP corresponding to the optimal cut-off of ≥2.76 and ≥48.06 (Youden) was 84.09% and 79.55%, respectively. Similarly, the specificity of VAI and LAP was 85.26% and 79.49%, respectively. VAI has a positive predictive value of 61.7% (95% CI [23.7%-40.3%]) and a negative predictive value of 95% (95% CI [88%-99.1%]). LAP has a positive predictive value of 53% (95% CI [40.3%-65.4%]) and a negative predictive value of 93.3% (95% CI [87.6%-96.9%]). PCOS women having VAI ≥ 2.76 had 19.3 times ([95% CI: 6.50-57.70]) more chance of developing MetS. PCOS women having LAP (≥48.06) have 3.7 times ([95% CI: 1.35-10.60]) more odds. There was no difference between ROC curves of VAI and LAP (P = 0.32). Conclusion: VAI cut-off ≥ 2.76 and LAP with a cut-off of ≥ 48.06 may be used as markers for predicting MetS amongst PCOS women.

3.
J Anaesthesiol Clin Pharmacol ; 40(1): 140-146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38666179

RESUMO

Background and Aims: Magnesium sulfate (MgSO4) has been demonstrated to have analgesic property in various clinical settings. This study explores if addition of MgSO4 to ropivacaine increases its analgesic efficacy when infiltrated continuously in the postsurgical wound following total abdominal hysterectomy. Material and Methods: This randomized controlled trial was conducted at a tertiary care referral hospital in New Delhi, India. Fifty-two patients were randomized into two groups to receive the intervention of which 48 were able to complete the study. The first group (n = 26) received 0.25% ropivacaine infiltration and the second group (n = 26) received 0.25% ropivacaine with 5% MgSO4 at the incision site for 48 h postoperatively. Primary objective was to compare the total postoperative opioid (morphine) consumption by the study participants in both the groups and the secondary objectives were pain scores at rest and at movement, patient satisfaction score, and wound quality of life on the 7th postoperative day among the two groups. Results: Both the groups were comparable in their demographic characteristics. The median morphine consumed at 48 h postoperatively was 16.5 [0-77] mg in the ropivacaine group and 13[1-45] mg in the ropivacaine with MgSO4 group and the difference was statistically insignificant (P = 0.788). There was no statistical difference between the groups with respect to the pain scores, patient satisfaction, or wound quality of life at 7 days. Conclusion: The addition of MgSO4 to ropivacaine does not confer any additional postoperative analgesic benefits over ropivacaine alone in continuous wound infiltration following total abdominal hysterectomy.

4.
Mol Neurobiol ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227271

RESUMO

Oligodendrocytes (OL) are the myelinating cells of the central nervous system that mediate nerve conduction. Loss of oligodendrocytes results in demyelination, triggering neurological deficits. Developing a better understanding of the cell signaling pathways influencing OL development may aid in the development of therapeutic strategies. The primary focus of this study was to investigate and elucidate the cell signaling pathways implicated in the developmental maturation of oligodendrocytes using human fetal neural stem cells (hFNSCs)-derived primary OL and MO3.13 cell line. Successful differentiation into OL was established by examining morphological changes, increased expression of mature OL markers MBP, MOG and decreased expression of pre-OL markers CSPG4 and O4. Analyzing transcriptional datasets (using RNA sequencing) in pre-OL and mature OL derived from hFNSCs revealed the novel and critical involvement of the JAK-STAT cell signaling pathway in terminal OL maturation. The finding was validated in MO3.13 cell line whose differentiation was accompanied by upregulation of IL-6 and the transcription factor STAT3. Increased phosphorylated STAT3 (pY705) levels were demonstrated by western blotting in hFNSCs-derived primary OL as well as terminal maturation in MO3.13 cells, thus validating the involvement of the JAK-STAT pathway in OL maturation. Pharmacological suppression of STAT3 phosphorylation (confirmed by western blotting) was able to prevent the increase of MBP-positive cells as demonstrated by flow cytometry. These novel findings highlight the involvement of the JAK-STAT pathway in OL maturation and raise the possibility of using this as a therapeutic strategy in demyelinating diseases.

5.
J Minim Access Surg ; 20(2): 207-215, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37357491

RESUMO

BACKGROUND AND OBJECTIVE: Female genital tuberculosis (FGTB) is an important type of extrapulmonary tuberculosis (TB) associated with morbidity especially infertility in developing countries. Laparoscopy may be difficult and hazardous in FGTB. The aim of the study was to observe the difficulties and complications of laparoscopy in FGTB cases. MATERIALS AND METHODS: It was a prospective study over 12 years' period on 412 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling for acid-fast bacilli (AFB) microscopy, culture, polymerase chain reaction (PCR), gene Xpert (last 212 cases) and histopathological evidence of epithelioid granuloma. Another 412 cases of diagnostic laparoscopy in the absence of FGTB performed during same time were taken as controls from the pool of non-TB cases. Various difficulties and complications were noted in both groups and statistical analysis was done. RESULTS: Mean age, parity, body mass index and duration of infertility were 26.8 versus 25.4 years, 0.32 versus 0.28, 23.15 versus 25.28 Kg/m 2 and 4.15 versus 5.12 years, respectively. Primary and secondary infertility was seen in 78.6% and 20.38% of cases in the study group and 74.75% and 25.24% in the control group, respectively. Endometrial biopsy showed AFB microscopy in 5.3%, culture in 6.3%, epithelioid granuloma in 15.77% and on peritoneal biopsy granuloma in 6.55%, positive PCR in 368 (89.32%) and positive gene Xpert in 38 out of 212 (17.92%, out of last 212 cases). Definite findings of FGTB were seen in 171 (41.50%) cases. Probable findings of FGTB were seen in 241 (58.49%) cases. Various complications were difficulty in the creation of pneumoperitoneum or insertion of trocar and cannula in 16.74% and 13.10% of cases as compared to 1.94% and 1.69% in the control group. Excessive bleeding was seen in 5.09% versus 0.97% cases, respectively. Various injuries observed were bowel injury in 1.69% versus 0.24% cases (small bowel in 1.21% vs. 0.24%, large bowel in 0.48% vs. 0.1%), while bladder injury was seen in 0.97% versus 0.24% cases, subacute intestinal obstruction was seen in 5.8% versus 0.72% cases respectively while flare up of TB was seen in 5.09% versus 0% in cases and controls, respectively. Wound infection was seen in 8.48% versus 1.25% cases, respectively. INTERPRETATION AND CONCLUSION: FGTB is associated with increased complications and difficulties as compared to laparoscopy in other cases.

6.
J Minim Access Surg ; 20(1): 24-29, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695245

RESUMO

BACKGROUND: Abdominopelvic tuberculosis (TB) is a variant of extrapulmonary TB causing significant morbidity, including infertility. MATERIALS AND METHODS: Results of 87 cases of diagnostic laparoscopy in cases of abdominopelvic TB diagnosed on composite reference standard (CRS) for demonstration of new laparoscopic white cotton ball sign are presented. RESULTS: Mean age, parity and duration of infertility were 27.2 years, 0.21 and 3.1 years, respectively. Oligomenorrhoea and hypomenorrhea were seen in 35 (40.22%) and 32 (36.78%) cases, while infertility was seen in all 87 (100%) cases while abdominal mass was seen in 27 (31.03%) cases and pelvic mass in 37 (42.58%) cases. Positive acid fast bacilli on microscopy and culture of endometrial biopsy was seen in 3.34% and 6.89% cases while epithelioid granuloma was seen in 12.64% cases on endometrial biopsy and in 13.79% cases on peritoneal biopsy. Positive polymerase chain reaction was seen in all cases while definitive abdominal pelvic TB was seen in 35 (40.1%) cases and probable findings in 42 (48.27%) cases. A new laparoscopic white cotton ball sign (resembling a large white cotton ball) was observed in 5 (5.74%) cases and biopsy from 3 showed it to be epithelioid granulomas positive. CONCLUSION: Demonstration of a new white cotton ball sign on laparoscopy seems to be a useful finding in abdominal pelvic TB.

7.
Int J Mol Sci ; 24(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37762545

RESUMO

The asymptomatic nature, high rate of disease recurrence, and resistance to platinum-based chemotherapy highlight the need to identify and characterize novel target molecules for ovarian cancer. Fibroblast growth factor 8 (FGF8) aids in the development and metastasis of ovarian cancer; however, its definite role is not clear. We employed ELISA and IHC to examine the expression of FGF8 in the saliva and tissue samples of epithelial ovarian cancer (EOC) patients and controls. Furthermore, various cell assays were conducted to determine how FGF8 silencing influences ovarian cancer cell survival, adhesion, migration, and invasion to learn more about the functions of FGF8. In saliva samples, from controls through low-grade to high-grade EOC, a stepped overexpression of FGF8 was observed. Similar expression trends were seen in tissue samples, both at protein and mRNA levels. FGF8 gene silencing in SKOV3 cells adversely affected various cell properties essential for cancer cell survival and metastasis. A substantial reduction was observed in the cell survival, cell adhesion to the extracellular matrix, migration, and adhesion properties of SKOV3 cells, suggesting that FGF8 plays a crucial role in the development of EOC. Conclusively, this study suggests a pro-metastatic function of FGF8 in EOC.


Assuntos
Recidiva Local de Neoplasia , Neoplasias Ovarianas , Humanos , Feminino , Fator 8 de Crescimento de Fibroblasto/genética , Fator 8 de Crescimento de Fibroblasto/metabolismo , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proliferação de Células
8.
Nucl Med Commun ; 44(10): 888-895, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37464877

RESUMO

INTRODUCTION: Heterogeneous and nonspecific symptoms make invasive endometriosis a difficult entity to diagnose. Small lesions with absent associated changes can be easily missed in cross-sectional imaging. Even when the lesions satisfy the thresholds for various investigations, their appearance changes with cyclical fluctuations in the hormonal levels. Therefore, newer approaches are needed to achieve correct diagnosis. METHODS: Six females in reproductive age group (mean age = 32.5 ±â€…4.3 years) were retrospectively selected, wherein the diagnosis of invasive endometriosis was confirmed after 18F-FDG-PET/CT. Indications for PET/CT were staging in 4 patients, suspected progression in 1 and suspected inflammatory bowel disease in one patient. The study was repeated in proliferative phase in two patients and in the menstrual phase in another patient. FNAC was available in two patients and a drop in CA125 was documented in the last patient. RESULTS: In five patients metabolically active lesions were seen in PET/CT and in the last, activity was absent despite symptoms. Repeat menstrual phase imaging in the last patient confirmed the diagnosis. In two patients with metabolically active lesions at baseline, resolution was seen in proliferative phase PET/CT. In the other two patients, repeat study was not indicated as FNAC revealed normal endometrial tissue and in the last patient, significant drop in CA125 was documented after just 2 weeks. In all of these patients, the final diagnosis was of invasive endometriosis. CONCLUSION: In reproductive-age women, PET/CT acquisition should be optimized in the context of menstrual cycle. This approach can be used to non-invasively rule in/rule out endometriosis, especially with repeat imaging in proper menstrual phase.


Assuntos
Endometriose , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Adulto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Endometriose/diagnóstico por imagem , Diagnóstico Ausente , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons , Fluordesoxiglucose F18
9.
Reprod Sci ; 30(12): 3456-3468, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37378824

RESUMO

Recurrent pregnancy loss (RPL) is a pervasive health issue affecting a large number of couples globally, which leads to increased emotional and financial strain on the affected families. While female factors have been extensively studied and are well known, the contribution of male factors to RPL remains largely unknown. As high as 40% of RPL cases are unexplained, which are termed as idiopathic RPL (iRPL), necessitating the investigation of male factors. The role of spermatozoa in early embryonic development is now well established, and recent research studies have shown that oxidative stress and DNA fragmentation in sperm cells are linked to RPL. The aim of this study was to identify proteomic markers of iRPL in human spermatozoa using tandem mass spectrometry. A label-free method quantified a total of 1820 proteins, and statistical analysis identified 359 differentially expressed proteins, the majority of which were downregulated in iRPL samples (344). Bioinformatics analysis revealed that proteomic alterations were mainly associated with biological processes such as response to stress, protein folding, chromatin organization, DNA conformation change, oxidative phosphorylation, and electron transport chain. In coherence with past studies, we determined fatty acid synthase (FASN) and clusterin (CLU) to be the most potential sperm markers for iRPL and confirmed their expression changes in iRPL by western blotting. Conclusively, we believe that FASN and CLU might serve as potential markers of iRPL and suggest exploratory functional studies to identify their specific role in pregnancy loss.


Assuntos
Aborto Habitual , Sêmen , Gravidez , Humanos , Masculino , Feminino , Sêmen/metabolismo , Clusterina/metabolismo , Proteômica/métodos , Espermatozoides/metabolismo , Aborto Habitual/genética , Ácido Graxo Sintases/metabolismo
10.
Indian J Med Res ; 157(2&3): 183-191, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37202937

RESUMO

Background & objectives: Female genital tuberculosis (FGTB) is an important variety of extrapulmonary TB causing significant morbidity, especially infertility, in developing countries like India. The aim of this study was to evaluate the laparoscopic findings of the FGTB. Methods: This was a cross-sectional study on 374 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling/biopsy for acid-fast bacilli, microscopy, culture, PCR, GeneXpert (only last 167 cases) and histopathological evidence of epithelioid granuloma. Diagnostic laparoscopy was performed in all the cases to evaluate the findings of FGTB. Results: Mean age, parity, body mass index and duration of infertility were 27.5 yr, 0.29, 22.6 kg/m2 and 3.78 years, respectively. Primary infertility was found in 81 per cent and secondary infertility in 18.18 per cent of cases. Endometrial biopsy was positive for AFB microscopy in 4.8 per cent, culture in 6.4 per cent and epithelioid granuloma in 15.5 per cent. Positive peritoneal biopsy granuloma was seen in 5.88 per cent, PCR in 314 (83.95%) and GeneXpert in 31 (18.56%, out of last 167 cases) cases. Definite findings of FGTB were seen in 164 (43.86%) cases with beaded tubes (12.29%), tubercles (32.88%) and caseous nodules (14.96%). Probable findings of FGTB were seen in 210 (56.14%) cases with pelvic adhesions (23.52%), perihepatic adhesions (47.86%), shaggy areas (11.7%), pelvic adhesions (11.71%), encysted ascites (10.42%) and frozen pelvis in 3.7 per cent of cases. Interpretation & conclusions: The finding of this study suggests that laparoscopy is a useful modality to diagnose FGTB with a higher pickup rate of cases. Hence it should be included as a part of composite reference standard.


Assuntos
Infertilidade Feminina , Laparoscopia , Tuberculose dos Genitais Femininos , Gravidez , Humanos , Feminino , Tuberculose dos Genitais Femininos/complicações , Tuberculose dos Genitais Femininos/diagnóstico , Tuberculose dos Genitais Femininos/patologia , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/epidemiologia , Estudos Transversais , Laparoscopia/efeitos adversos , Granuloma
11.
Antioxidants (Basel) ; 12(3)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36978882

RESUMO

The overproduction of reactive oxygen species (ROS) has been associated with various human diseases. ROS exert a multitude of biological effects with both physiological and pathological consequences. Monosodium glutamate (MSG), a sodium salt of the natural amino acid glutamate, is a flavor-enhancing food additive, which is widely used in Asian cuisine and is an ingredient that brings out the "umami" meat flavor. MSG consumption in rats is associated with ROS generation. Owing to its consumption as part of the fast-food culture and concerns about its possible effects on pregnancy, we aimed to study the impact of MSG on placental trophoblast cells. MSG exposure influenced trophoblast invasion and differentiation, two of the most critical functions during placentation through enhanced production of ROS. Similar findings were also observed on MSG-treated placental explants, as confirmed by elevated Nrf2 levels. Ultrastructural studies revealed signs of subcellular injury by MSG exposure. Mechanistically, MSG-induced oxidative stress with endoplasmic reticulum stress pathways involving Xbp1s and IRE1α was observed. The effect of MSG through an increased ROS production indicates that its long-term exposure might have adverse health effect by compromising key trophoblast functions.

12.
Mol Neurobiol ; 60(5): 2910-2921, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36749560

RESUMO

Fetal neural stem cells (FNSCs) present in the human fetal brain differentiate into cells of neuronal and glial lineages. The developing fetus is exposed to lower oxygen concentrations than adults, and this physiological hypoxia may influence the growth and differentiation of the FNSCs. This study aimed to evaluate the effect of hypoxia on the differentiation potential of human FNSCs isolated from the subventricular zone of aborted fetal brains (n = 5). FNSCs were isolated, expanded, and characterized by Nestin and Sox2 expression using immunocytochemistry and flow cytometry, respectively. These FNSCs were exposed to 20% oxygen (normoxia) and 0.2% oxygen (hypoxia) concentrations for 48 h, and hypoxia exposure (n = 5) was validated. Whole transcriptome analyses (Genespring GX13) of FNSCs exposed to hypoxia (Agilent 4 × 44 K human array slides) highlighted that genes associated with neurogenesis were enriched upon exposure to hypoxia. The pathway analysis of these enriched genes (using Metacore) showed the involvement of the WNT signaling pathway. Microarray analyses were validated using neuronal and glial lineage commitment markers, namely, NEUROG1, NEUROG2, ASCL1, DCX, GFAP, OLIG2, and NKX2.2, using qPCR (n = 9). DCX, ASCL1, NGN1, and GFAP protein expression was analyzed by Western blotting (n = 3). This demonstrated upregulation of the neuronal commitment markers upon hypoxia exposure, while no change was observed in astrocytic and oligodendrocyte lineage commitment markers. Increased expression of downstream targets of the WNT signaling pathway, TCF4 and ID2, by qPCR (n = 9) and increased protein expression of CTNNB1 (ß-catenin) and ID2 by Western blot (n = 3) indicated its involvement in mediating neuronal differentiation upon exposure to hypoxia.


Assuntos
Células-Tronco Neurais , Via de Sinalização Wnt , Humanos , Células Cultivadas , Células-Tronco Neurais/metabolismo , Neurogênese , Diferenciação Celular , Feto , Hipóxia/metabolismo , Oxigênio/farmacologia , Oxigênio/metabolismo
14.
Am J Reprod Immunol ; 89(2): e13632, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36494901

RESUMO

BACKGROUND: Female genital tuberculosis (FGTB), an important clinical sub-type of extra-pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity. AIMS: This review tries to elucidates the role of various immune factors in FGTB and LGTB. CONTENT: Various immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa-B (NF-KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti-tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in-vitro fertilization and embryo transfer may be required for some women. IMPLICATIONS: Inflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.


Assuntos
Infertilidade Feminina , Tuberculose dos Genitais Femininos , Gravidez , Feminino , Humanos , Tuberculose dos Genitais Femininos/diagnóstico , Tuberculose dos Genitais Femininos/tratamento farmacológico , Tuberculose dos Genitais Femininos/patologia , Infertilidade Feminina/tratamento farmacológico , Etambutol/uso terapêutico , Fertilização in vitro , Tubas Uterinas/patologia
15.
Am J Reprod Immunol ; 89(2): e13670, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36565013

RESUMO

Hypertensive disorders of pregnancy (HDP) are one of the commonest maladies, affecting 5%-10% of pregnancies worldwide. The American College of Obstetricians and Gynecologists (ACOG) identifies four categories of HDP, namely gestational hypertension (GH), Preeclampsia (PE), chronic hypertension (CH), and CH with superimposed PE. PE is a multisystem, heterogeneous disorder that encompasses 2%-8% of all pregnancy-related complications, contributing to about 9% to 26% of maternal deaths in low-income countries and 16% in high-income countries. These translate to 50 000 maternal deaths and over 500 000 fetal deaths worldwide, therefore demanding high priority in understanding clinical presentation, screening, diagnostic criteria, and effective management. PE is accompanied by uteroplacental insufficiency leading to vascular and metabolic changes, vasoconstriction, and end-organ ischemia. PE is diagnosed after 20 weeks of pregnancy in women who were previously normotensive or hypertensive. Besides shallow trophoblast invasion and inadequate remodeling of uterine arteries, dysregulation of the nonimmune system has been the focal point in PE. This results from aberrant immune system activation and imbalanced differentiation of T cells. Further, a failure of tolerance toward the semi-allogenic fetus results due to altered distribution of Tregs such as CD4+FoxP3+ or CD4+CD25+CD127(low) FoxP3+ cells, thereby creating a cytotoxic environment by suboptimal production of immunosuppressive cytokines like IL-10, IL-4, and IL-13. Also, intracellular production of complement protein C5a may result in decreased FoxP3+ regulatory T cells. With immune system dysfunction as a major driver in PE pathogenesis, it is logical that therapeutic targeting of components of the immune system with pharmacologic agents like anti-inflammatory and immune-modulating molecules are either being used or under clinical trial. Cholesterol synthesis inhibitors like Pravastatin may improve placental perfusion in PE, while Eculizumab (monoclonal antibody inhibiting C5) and small molecular inhibitor of C5a, Zilucoplan are under investigation. Monoclonal antibody against IL-17(Secukinumab) has been proposed to alter the Th imbalance in PE. Autologous Treg therapy and immune checkpoint inhibitors like anti-CTLA-4 are emerging as new candidates in immune horizons for PE management in the future.


Assuntos
Hipertensão Induzida pela Gravidez , Morte Materna , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/terapia , Pré-Eclâmpsia/metabolismo , Placenta/metabolismo , Fatores de Transcrição Forkhead
16.
J Midlife Health ; 14(4): 291-298, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38504731

RESUMO

Background: Metabolic syndrome (MS) is a spectrum of disorders that includes dysglycemia, dyslipidemia, central obesity, and hypertension. South Asian Indians are more prone to harbor MS at a younger age compared to Caucasians. However, there is a lack of large-scale data correlating menopause to MS in South Asian settings. Aims and Objectives: The study aimed to determine the prevalence of MS and its components in pre- and postmenopausal women. It also assessed the relationship of age, menopausal status, personal and family history, anthropometric parameters, and biochemical markers to MS. Materials and Methods: It was an interim analysis of a multicountry cross-sectional study in the South Asian Federation of Menopause Society (SAFOMS) countries: India, Pakistan, Bangladesh, Nepal, and Sri Lanka conducted through both online and physical methods. The survey questionnaire consisted of questions about details of personal history, demographics, and family history related to MS. Anthropometric measurements such as height, weight, basal metabolic index (BMI), waist circumference, and blood pressure readings were noted. Relevant history, history of polycystic ovarian syndrome, hypertensive disorders of pregnancy, and vasomotor symptoms were enquired. Biochemical evaluation of markers associated with MS was undertaken. Results: In this interim analysis, 638 women were recruited. Out of them, 406 (63.6%) women were premenopausal and 232 (36.4%) were postmenopausal. 392 (61.4%) women had MS, while 246 (38.6%) women did not have MS. Increasing age, BMI, and visceral adiposity (waist circumference) were significantly correlated with incidence of MS. Raised fasting blood sugar, hemoglobin A1C, total cholesterol, low-density lipoprotein, serum triglyceride, and reduced high-density lipoprotein levels were significantly associated with the incidence of MS in both pre- and postmenopausal women. Peri- and postmenopausal hot flashes, night sweats, and sleep disturbances were also significantly associated with MS. Personal history of hypertension, diabetes, and dyslipidemia were the strongest factors to be associated with MS with a significantly high odds ratio. Conclusion: The study has highlighted the role of BMI and waist circumference as the first warning signs, which will encourage to go for regular biochemical screening through lipid profile and fasting blood glucose measurements. Our study is a stepping stone for all future studies for relation of menopause to MS.

17.
J Midlife Health ; 13(2): 139-144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276623

RESUMO

Background: Stress urinary incontinence (SUI) is a common ailment in affecting quality of life. This study was performed to see role of incontinence severity index (ISI) in evaluating severity of SUI and to see the impact of treatment of SUI. Materials and Methods: A total of 40 women with the diagnosis of SUI on history and clinical examination were enrolled. ISI was calculated on all the women before treatment. All women were treated with either conservative treatment (pelvic floor exercises, life style modification, and duloxetine therapy) (4, 10%) or Burch's colposuspension (18, 45%) or tension-free obturator tape (18, 45%) as per clinical situation after discussion with patients. ISI was again calculated 6 months after treatment. Results: Mean age, parity, body mass index in the study were 41.60 years, 2.73, and 24.2 kg/m2, respectively. All 40 (100%) patients had SUI with the mean duration of symptoms being 4.04 years. A total of 11 (27.5%) had moderate SUI (ISI 3-6), while 24 (60%) had severe SUI (ISI 8-9), while 5 (12.5%) had very severe SUI (ISI 12). Range of pretreatment ISI was 3-12 with mean being 8.8 ± 3.2. Posttreatment ISI reduced significantly with range of 1-4 and mean of 1.3 ± 0.4 (P < 0.001). The reduction was significant for all the groups, but there was no significant difference in efficacy of three treatment groups. Statistical analysis was done using SPSS IBM Version 2-1-0 using Chi-square test, Fisher's Extract test, and ANOVA test as appropriate. Conclusion: ISI is a useful modality to evaluate the severity of SUI and to see the impact of treatment modalities on SUI.

18.
Twin Res Hum Genet ; 25(3): 156-164, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35786423

RESUMO

Nature and nurture have always been a prerogative of evolutionary biologists. The environment's role in shaping an organism's phenotype has always intrigued us. Since the inception of humankind, twinning has existed with an unsettled parley on the contribution of nature (i.e. genetics) versus nurture (i.e. environment), which can influence the phenotypes. The study of twins measures the genetic contribution and that of the environmental influence for a particular trait, acting as a catalyst, fine-tuning the phenotypic trajectories. This is further evident because a number of human diseases show a spectrum of clinical manifestations with the same underlying molecular aberration. As of now, there is no definite way to conclude just from the genomic data the severity of a disease or even to predict who will get affected. This greatly justifies initiating a twin registry for a country as diverse and populated as India. There is an unmet need to set up a nationwide database to carefully curate the information on twins, serving as a valuable biorepository to study their overall susceptibility to disease. Establishing a twin registry is of paramount importance to harness the wealth of human information related to the biomedical, anthropological, cultural, social and economic significance.


Assuntos
Doenças em Gêmeos , Gêmeos , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Humanos , Índia/epidemiologia , Sistema de Registros , Gêmeos/genética , Recursos Humanos
19.
Taiwan J Obstet Gynecol ; 61(2): 201-209, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35361377

RESUMO

The ongoing COVID-19 pandemic is raising great concern all over the world. The recent introduction of vaccines has offered reason for optimism, however, new issues have arisen, such as vaccine reluctance. The safety of vaccines for pregnant women is one of the most serious of these concerns. The purpose of this review article is to provide updated international vaccine recommendations, results of ongoing studies and clinical trials, and the role of gynecologists in counseling the women to understand the risks versus benefits as well as form an informed decision towards vaccine acceptance for COVID-19. Although COVID-19 infection increases the risk of severe morbidity and mortality in pregnant women, pregnant women were not included in the initial vaccine trials. As a result, safety information is scarce. Nations have differing recommendations, though many have recently approved the COVID-19 immunization in pregnancy following a risk-benefit analysis. The Joint Committee on Vaccination and Immunization (JCVI) of the United Kingdom recently approved an mRNA vaccination for pregnant women. Vaccination is recommended by the CDC, ACOG, ARFM, and WHO. India recently took a stand, with the ICMR and the Ministry of Health and Family Welfare recommending vaccination during pregnancy and lactation.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Influenza Humana/epidemiologia , Pandemias/prevenção & controle , Gravidez
20.
Genes (Basel) ; 13(3)2022 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-35328060

RESUMO

Hypoxic ischemic injury to the fetal and neonatal brain is a leading cause of death and disability worldwide. Although animal and culture studies suggest that glutamate excitotoxicity is a primary contributor to neuronal death following hypoxia, the molecular mechanisms, and roles of various neural cells in the development of glutamate excitotoxicity in humans, is not fully understood. In this study, we developed a culture model of human fetal neural stem cell (FNSC)-derived astrocytes and examined their glutamate uptake in response to hypoxia. We isolated, established, and characterized cultures of FNSCs from aborted fetal brains and differentiated them into astrocytes, characterized by increased expression of the astrocyte markers glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 1 (EAAT1) and EAAT2, and decreased expression of neural stem cell marker Nestin. Differentiated astrocytes were exposed to various oxygen concentrations mimicking normoxia (20% and 6%), moderate and severe hypoxia (2% and 0.2%, respectively). Interestingly, no change was observed in the expression of the glutamate transporter EAAT2 or glutamate uptake by astrocytes, even after exposure to severe hypoxia for 48 h. These results together suggest that human FNSC-derived astrocytes can maintain glutamate uptake after hypoxic injury and thus provide evidence for the possible neuroprotective role of astrocytes in hypoxic conditions.


Assuntos
Astrócitos , Ácido Glutâmico , Células-Tronco Neurais , Astrócitos/metabolismo , Hipóxia Celular , Células Cultivadas , Transportador 1 de Aminoácido Excitatório/genética , Transportador 1 de Aminoácido Excitatório/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Células-Tronco Neurais/metabolismo
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