Placental Alkaline Phosphatase Research Articles

Extracellular Vesicles From Women With Severe Preeclampsia Impair Vascular Endothelial Function.

Preeclampsia (PE) manifesting as hypertension and organ injury is mediated by vascular dysfunction. In biological fluids, extracellular vesicles (EVs) containing microRNA (miRNA), protein, and other cargo released from the placenta may serve as carriers to propagate injury, altering the functional phenotype of endothelial cells. PE has been consistently correlated with increased levels of placenta-derived EVs (pEVs) in maternal circulation. However, whether pEVs impaired endothelial cell function remains to be determined. In this study, we hypothesize that pEVs from pregnant women with severe PE (sPE) impair endothelial function through altered cell signaling. We obtained plasma samples from women with sPE (n = 14) and normotensive pregnant women (n = 15) for the isolation of EVs. The total number of EV and pEV contribution was determined by quantifying immunoreactive EV-cluster of designation 63 (CD63) and placental alkaline phosphatase (PLAP) as placenta-specific markers, respectively. Vascular endothelial functional assays were determined by cell migration, electric cell-substrate impedance sensing in human aortic endothelial cells (HAECs), and wire myography in isolated blood vessels, preincubated with EVs from normotensive and sPE women. Plasma EV and pEV levels were increased in sPE when compared to normotensive without a significant size distribution difference in sPE (108.8 ± 30.2 nm) and normotensive-EVs (101.3 ± 20.3 nm). Impaired endothelial repair and proliferation, reduced endothelial barrier function, reduced endothelial-dependent vasorelaxation, and decreased nitrite level indicate that sPE-EVs induced vascular endothelial dysfunction. Moreover, sPE-EVs significantly downregulated endothelial nitric oxide synthase (eNOS and p-eNOS) when compared to normotensive-EV. EVs from sPE women impair endothelial-dependent vascular functions in vitro.

Clinical significance of predictive and diagnostic indices of fetal pathology associated with placental insufficiency in women with endometriosis

BACKGROUND: Modern achievements of pharmacology, surgery and reproductive medicine have determined an increase in the implementation of reproductive function in endometriosis of various localization. The onset of pregnancy in presence of impaired endometrial receptivity and progesterone resistance, pro-inflammatory and pro-thrombotic status, abnormal functioning of the immune system, structural changes in the reproductive organs leads to impaired formation of the embryo (feto) placental system, early reproductive losses, complicated pregnancy and adverse perinatal outcomes. In this regard, the endometriosis and pregnancy issue requires close study and specific proposals to optimize pregnancy management.
 AIM: The aim of this study was to develop predictive (PIs) and diagnostic (DIs) indices of placenta-associated fetal pathology in pregnant women with endometriosis, to determine their prognostically and diagnostically significant parameters.
 MATERIALS AND METHODS: This prospective study in the dynamics of gestation included a comprehensive clinical and laboratory examination of 175 pregnant women with endometriosis (100 subjects with adenomyosis and 75 subjects with ovarian endometriosis). To develop PIs and DIs, two comparison groups with fetal pathology due to placental insufficiency were retrospectively identified, depending on the location of endometriosis. Group I consisted of 49 pregnant women with adenomyosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia; Group II comprised 29 pregnant women with ovarian endometriosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia. The control group (Group III) included 30 healthy pregnant women with a normal course of gestation. The examination was performed at 10-14 weeks, 20-24 weeks, and 28-34 weeks of gestation and included an assessment of placental insufficiency markers such as placental growth factor (PlGF), placental -1-microglobulin (PAMG-1), tumor necrosis factor (TNF), lymphocytes with membrane receptor FasR (L CD95+), C-reactive protein, placental alkaline phosphatase (PAPh), and fetal hemoglobin (HbF). The information value of individual parameters and indices was determined by ROC analysis, odds ratio, and clinical epidemiology tests.
 RESULTS: Pregnancy in presence of endometriosis in 100% of cases was complicated by placental insufficiency of varying severity (with fetal pathology in 81.5% of cases), the frequency of which had statistically significant differences between the groups of pregnant women with adenomyosis and ovarian endometriosis (2 = 4.06, p = 0.04). To predict growth retardation and / or chronic fetal hypoxia, we have developed PI I (PlGF / TNF 100) and PI II (PAMG-1 / PlGF 100), which characterize the state of placental angio-and vasculogenesis depending on systemic inflammatory response level. For early diagnosis of fetal pathology, we have proposed DI I (CRP / PAPh 100), DI II (HbF / PlGF 100) and DI III (L CD95+ / PAPh 100), which allow for diagnosing placental alterations with impaired placental energy supply due to an increase in inflammatory status. Evaluation of prognostic and diagnostic significance of PIs and DIs showed that the most informative tools are PI I (Se = 86.1%, Sp = 80.5%) and DI I (Se = 88.3%, Sp = 83.7%).
 CONCLUSIONS: The use of PIs allows for risk stratification of pregnant women from the 1st trimester of gestation to address the issue of the prevention method. The clinical capabilities of DIs optimize obstetric tactics for the timely prescription of therapy for placental insufficiency and targeted diagnosis of fetal pathology. Pregnant women with endometriosis should be classified as a high perinatal risk group, and therefore the proposed PIs and DIs should be included in the dynamic examination complex.

Evaluation of Placental Alkaline Phosphatase Expression as A Potential Target of Solid Tumors Immunotherapy by Using Gene and Protein Expression Repositories.

Placental alkaline phosphatase (PLAP) is a membrane enzyme mainly expressed in the placenta. PLAP is shown to be expressed in ovarian cancer (OV), however, there is little known about its expression in other cancers. Using gene and protein expression deposited data, we surveyed PLAP expression across malignant and normal human tissues to explore the potential of PLAP as an immunotherapy target. We detected more than two-fold increased PLAP expression in multiple solid tumors including ovarian cancer, testicular germ cell tumors (TGCT), and uterine corpus endometrial carcinoma (UCEC) compared with matched normal tissues. We also showed association of PLAP expression with high mortality pancreatic adenocarcinoma (PAAD). Altogether, our results suggest that PLAP can be a promising target for immunotherapy of multiple cancers, especially OV, TGCT, and UCEC.

Specific Inhibitor of Placental Alkaline Phosphatase Isolated from a DNA-Encoded Chemical Library Targets Tumor of the Female Reproductive Tract.

Placental alkaline phosphatase (PLAP) is an abundant surface antigen in the malignancies of the female reproductive tract. Nevertheless, the discovery of PLAP-specific small organic ligands for targeting applications has been hindered by ligand cross-reactivity with the ubiquitous tissue non-specific alkaline phosphatase (TNAP). In this study, we used DNA-encoded chemical libraries to discover a potent (IC50 = 32 nM) and selective PLAP inhibitor, with no detectable inhibition of TNAP activity. Subsequently, the PLAP ligand was conjugated to fluorescein; it specifically bound to PLAP-positive tumors in vitro and targeted cervical cancer in vivo in a mouse model of the disease. Ultimately, the fluorescent derivative of the PLAP inhibitor functioned as a bispecific engager redirecting the killing of chimeric antigen receptor-T cells specific to fluorescein on PLAP-positive tumor cells.

Immunohistochemical insights into a hidden pathology: Canine cryptorchidism

Cryptorchidism is a common disorder in the canine population with some aspects still unclear. Although the bilateral condition is known to lead to fertility problems and predisposition to testicular cancer, the neoplastic risk for scrotal testis in unilateral cryptorchid dog is controversial. Therefore, the therapeutic approach to the canine unilateral cryptorchid is arbitrary so far.This study aimed to investigate precancerous testicular lesions, such as immaturity and atrophy, and compare them in scrotal and undescended testes using an in-depth diagnostic analysis based on immunophenotypic patterns. With this purpose, 26 adult male dogs of different ages and breeds, affected by unilateral or bilateral cryptorchidism were enrolled. After surgical removal, testes were examined immunohistochemically to assess their positivity for specific markers of the canine foetal/neonatal period, that is vimentin (VIM), cytokeratin (CK), desmin (DES), inhibin-α (INH), and anti-Müllerian hormone (AMH) in Sertoli cells, and placental alkaline phosphatase (PLAP) in germ cells. Except for the ubiquitous VIM, all the markers were more expressed in neoplastic gonads compared to healthy ones (P < 0.05). Similarly, testes detected with Sertoli cell-only tubules as well as with Sertoli cells hyperplasia showed higher expression than gonads without such alterations for CK, DES, AMH and PLAP, and for CK and DES, respectively (P < 0.05). The same trend was observed in undescended respect to scrotal testes even though their positivity was significant only for DES, INH and AMH (P < 0.05). Immunohistochemical positivity found in scrotal testes of unilateral cryptorchid dogs, even in absence of detectable anatomical abnormalities, was suggestive of precancerous lesions.Despite the limited sample size, this study could help to clarify the predisposition to neoplastic development in normally descended testes. These markers expression in adult life could allow identifying the early stages of the testicular carcinogenesis process besides suggesting a precautionary bilateral surgical approach in unilateral cryptorchid dogs.

Circulating Placental Vesicles Carry HLA-DR in Pre-Eclampsia: A New Potential Marker of the Syndrome.

BackgroundPre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women.Methodsperipheral venous blood was collected from 22 women with PE and 22 normal pregnant women. Circulating STBEVs were collected by ultra-centrifugation (120000 g) and analyzed for the expression of HLA-DR and placental alkaline phosphatase (PLAP), a specific marker of the placenta, by Western blot analysis and flow cytometry.Resultscirculating STBEVs positive for HLA-DR were observed in 64% of PE women while no HLA-DR positivity was detected in any of the controls (P<0.01).ConclusionsAberrant expression of HLA-DR in circulating STBEVs is specifically associated to PE. Further studies are required: a) to define the role of aberrant placental expression of HLA-DR molecules in the pathogenesis of PE; b) evaluate a possible application of detecting circulating HLA-DR positive STBEVs in the diagnosis and prediction of PE in the first and second trimester of pregnancy.

In Vivo Calcium Imaging Visualizes Incision-Induced Primary Afferent Sensitization and Its Amelioration by Capsaicin Pretreatment.

Previous studies have shown that infiltration of capsaicin into the surgical site can prevent incision-induced spontaneous pain like behaviors and heat hyperalgesia. In the present study, we aimed to monitor primary sensory neuron Ca2+ activity in the intact dorsal root ganglia (DRG) using Pirt-GCaMP3 male and female mice pretreated with capsaicin or vehicle before the plantar incision. Intraplantar injection of capsaicin (0.05%) significantly attenuated spontaneous pain, mechanical, and heat hypersensitivity after plantar incision. The Ca2+ response in in vivo DRG and in in situ spinal cord was significantly enhanced in the ipsilateral side compared with contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in capsaicin-pretreated animals detected by immunohistochemistry and placental alkaline phosphatase (PLAP) staining. Thus, capsaicin pretreatment attenuates incisional pain by suppressing Ca2+ response because of degeneration of primary sensory nerve fibers in the skin.SIGNIFICANCE STATEMENT Postoperative surgery pain is a major health and economic problem worldwide with ∼235 million major surgical procedures annually. Approximately 50% of these patients report uncontrolled or poorly controlled postoperative pain. However, mechanistic studies of postoperative surgery pain in primary sensory neurons have been limited to in vitro models or small numbers of neurons. Using an innovative, distinctive, and interdisciplinary in vivo populational dorsal root ganglia (DRG) imaging (>1800 neurons/DRG) approach, we revealed increased DRG neuronal Ca2+ activity from postoperative pain mouse model. This indicates widespread DRG primary sensory neuron plasticity. Increased neuronal Ca2+ activity occurs among various sizes of neurons but mostly in small-diameter and medium-diameter nociceptors. Capsaicin pretreatment as a therapeutic option significantly attenuates Ca2+ activity and postoperative pain.

Pattern of placental alkaline phosphatase (PLAP) expression in human tumors: a tissue microarray study on 12,381 tumors.

Placental alkaline phosphatase (PLAP) is commonly expressed at high levels in testicular germ cell tumors. PLAP immunohistochemistry (IHC) is thus often used to confirm this diagnosis, especially in cases of putative metastasis. However, other tumors can also express PLAP. To comprehensively determine PLAP expression in normal and tumor tissue, a tissue microarray containing 16,166 samples from 131 different tumor types and subtypes as well as 608 samples from 76 different normal tissue types was analyzed by IHC. Moderate to strong PLAP positivity was found in 27 (21%) of 131 different tumor types including seminoma (96%), embryonal carcinoma (85%), and yolk sac tumors of the testis (56%); endometrioid carcinoma of the endometrium (28%) and the ovary (20%); gastric adenocarcinoma (22%); serous carcinoma (not otherwise specified) of the ovary (17%) and the uterus (11%); adenocarcinoma of the ampulla of Vater (15%); carcinosarcoma of the ovary (11%) and the uterus (8%); esophageal adenocarcinoma (10%); invasive urothelial carcinoma (4%); cholangiocarcinoma (2%); and adenocarcinoma of the lung (1%). Low‐level PLAP immunostaining, often involving only a small fraction of tumor cells, was seen in 21 additional tumor entities. The clinical significance of PLAP expression may vary between tumor types as high PLAP expression was linked to advanced pathological tumor stage (p = 0.0086), nodal metastasis (p = 0.0085), and lymphatic (p = 0.0007) and blood vessel invasion (p = 0.0222) in colorectal cancer, but to low pathological tumor stage in endometrial cancer (p = 0.0043). In conclusion, our data identify several tumor entities that can show PLAP expression at comparable levels to testicular germ cell tumors. These tumor entities need to be considered in cases of PLAP‐positive metastasis. Low‐level PLAP expression can be found in various other tumor entities and should generally not be viewed as a strong argument for germ cell neoplasia.

Ascending spinal tract formation in chick embryo originating from different spinal regions

The present study aimed to assess spinal tract formation in neurons originating from cervical (C7), brachial (C14), and thoracic (T4) regions, with the lumbar (LS2) region as a reference, in a chick embryo. For the assessment of the spinal tracts, we introduced a vector expressing human placental alkaline phosphatase into progenitor cells generated after neural tube closure and belonging to the above segments, using in ovo electroporation. The ascending axons took primarily similar paths: dorsal commissural, ventral commissural, and dorsal non-commissural paths, with some variance depending on their originating segments. Some populations of non-commissural neurons later extended their axons following a ventral path. The elongation rates of these axons are primarily constant and tended to increase over time; however, some variations depending on the originating segments were also observed. Some of the dorsally ascending axons entered into the developing cerebellum, and spinocerebellar neurons originating from T4 projected their axons into the cortex of the cerebellum differently from those from LS2. These results unveil an overall picture of early ascending spinal tract formation.

Abstract 2548: Preclinical development of EARLI-001, a genetic platform producing cancer-activated synthetic biomarkers for the early detection of malignancies

Abstract Early detection of cancer is a powerful driver of increased survival rate, quality of life and reduced healthcare costs. ‘Liquid biopsies' that rely upon chemistry for the detection of blood-based endogenous cancer biomarkers such as proteins, circulating tumor DNA or RNA show only limited sensitivity for certain early stage cancers where the tumor mass shedding those biomarkers is smaller. Rather than searching for elusive natural biomarkers shed into the bloodstream, we are employing a promising alternate approach rooted in biology to usurp the highly dysregulated transcriptional pathways that give rise to malignancies to force cancer cells to produce easily detectable ‘synthetic' biomarkers that do not naturally occur. EARLI-001 is a DNA nanoplasmid comprised of a cancer-activated promoter to drive expression of Secreted Embryonic Alkaline Phosphatase (SEAP). The survivin promoter was initially selected for proof of concept because the corresponding anti-apoptotic gene product is widely overexpressed in many cancers, including melanoma, liver, breast, lung, colon and ovarian cancer, while not being expressed in normal adult tissues. The synthetic biomarker SEAP is a secreted variant of human placental alkaline phosphatase, which is only expressed during fetal development and thus has near-zero background in adult blood. EARLI-001 is formulated using a non-viral linear polyethyleneimine and administered intravenously to enable broad tissue distribution and transient transfection of multiple tissues. The sensitivity and specificity of EARLI-001 for tumor detection were established using a variety of cell-derived xenograft models. A single administration of EARLI-001 in immunocompromised mice bearing a modest burden of lung metastases drove cancer-activated SEAP expression that was at least 100-fold higher than the corresponding expression in non-tumor bearing animals. In an immune-competent syngeneic model, EARLI-001 produced 10-fold higher SEAP expression in mice bearing lung metastases of 4T1 mammary tumor cells than naïve mice. EARLI-001 could also discriminate mice bearing orthotopic Hep3B liver xenograft tumors from naïve control mice. Finally, the sensitivity of EARLI-001 in detecting small tumors was demonstrated in a longitudinal study, in which robust cancer-specific SEAP expression occurred even when the lung tumor burden was too low to result in significant changes in organ weight. The toxicology, pharmacokinetics, and biodistribution of EARLI-001 were evaluated in several GLP studies in mice as well as canines, enabling translation to a first-in-man clinical study. This Phase 1 dose escalation study will evaluate the safety, tolerability and PK/PD of EARLI-001 in subjects with locally advanced or metastatic lung cancer and enable further clinical development of the cancer-activated synthetic biomarker platform. Citation Format: Badriprasad Ananthanarayanan, Regina Nieu, Evan Bishop, Shireen Rudina, Alex Harwig, Bijee George, David Suhy. Preclinical development of EARLI-001, a genetic platform producing cancer-activated synthetic biomarkers for the early detection of malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2548.

Is cervical swab an efficient method for developing a new noninvasive prenatal diagnostic test for numerical and structural chromosome anomalies?

Background/aim Prenatal diagnosis is vital to obtain healthy generation for risky pregnancies. There have been several approaches, some of which are routinely applied in clinics to evaluate the possible prenatal deficiencies and/or diseases. In the present study, we aimed to isolate the fetal cells from endocervical samples and try to identify possible anomalies which were proved by Amniocentesis (AS) and chorionic villus sampling (CVS) methods.Materials and methodsEndoservical specimens were collected from 100 pregnant women. Cells were separated in parallel by fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) using human leukocyte antigen (HLA) G233 and placental alkaline phosphatase (PLAP) antibodies. CMA (comprehensive meta-analysis) were carried out and male fetuses were confirmed with Sex determining region Y (SRY) amplification.Results The percent of HLA G233 and placental and placental alkaline phosphatase (PLAP) positive cells were 4.55% and 84.59%, respectively. The percent of cells positive for both markers was 14.75%. CMA analyses were not informative. (SRY) was amplified in 67% of the samples.Conclusion However, the success rate of the both cell sorting and scanning of DNA anomalies by aCGH and/or RT-PCR was limited, preventing the applicability of this proposal in the clinics. Still, the success of the proposed method depends on the development of the novel fetal cell-specific antibodies and the improvements in the sorting systems.

Thalamic germinoma: A case report

Germinomas involving non-midline structures such as thalamus and basal ganglia are relatively uncommon contributing up to 5–10% of all intracranial germ cell tumors. Here, we describe a case of thalamic germinoma in a 16-year-old boy who presented with recurrent episodes of headache and blurry vision for 2 months. Magnetic resonance imaging revealed heterogenous mass in the left thalamus with contrast enhancement causing mass effect and obstructive hydrocephalus. Total excision of the tumor was done by suboccipital craniotomy. Histopathology showed poorly differentiated round cells with vacuolated cytoplasm, round nuclei with prominent nucleoli which were separated by thin fibrovascular stroma infiltrated by lymphocytes. Immunohistochemistry showed diffuse immunoreactivity for placental alkaline phosphatase and octamer-binding transcription factor 3/4, and negative for glial fibrillary acidic protein, cluster of differentiation (CD)-45, and CD-30, confirming it to be a pure germinoma. With a combined approach of surgery, chemotherapy, and radiotherapy, these patients have better long-term survival rates.

Pattern of placental alkaline phosphatase (PLAP) expression in human tumours: a tissue microarray study on 12,381 tumours

Pattern of placental alkaline phosphatase (PLAP) expression in human tumours: a tissue microarray study on 12,381 tumours

Biochemical Importance and Kinetic Studies of Placental Alkaline Phosphatase Isoenzyme as a Predictor Marker of Primary Malignancies

ung cancer is the main cause of cancer-related death worldwide and conventional diagnostic strategies must be improved. developments of a simple method or techniques which would enable researchers to identify and validate the early screening biomarker of lung cancer patients. The aims of this article were to review the background documents on the state of the art of the scientific literature in studies that used Placental alkaline phosphatase in the diagnostic of lung cancer also to suggest areas where further research is needed, either to deal with gaps in the knowledge related to employ the heat stability of Placental alkaline phosphatase or assessment the quantitation methods of the isoenzyme.

Gingival Crevicular Placental Alkaline Phosphatase Is an Early Pregnancy Biomarker for Pre-Eclampsia.

Early and innovative diagnostic strategies are required to predict the risk of developing pre-eclampsia (PE). The purpose of this study was to evaluate the performance of gingival crevicular fluid (GCF) placental alkaline phosphatase (PLAP) concentrations to correctly classify women at risk of PE. A prospectively collected, retrospectively stratified cohort study was conducted, with 412 pregnant women recruited at 11–14 weeks of gestation. Physical, obstetrical, and periodontal data were recorded. GCF and blood samples were collected for PLAP determination by ELISA assay. A multiple logistic regression classification model was developed, and the classification efficiency of the model was established. Within the study cohort, 4.3% of pregnancies developed PE. GCF-PLAP concentration was 3- to 6-fold higher than in plasma samples. GCF-PLAP concentrations and systolic blood pressure were greater in women who developed PE (p = 0.015 and p < 0.001, respectively). The performance of the multiparametric model that combines GCF-PLAP concentration and the levels of systolic blood pressure (at 11–14 weeks gestation) showed an association of systolic blood pressure and GCF-PLAP concentrations with the likelihood of developing PE (OR:1.07; 95% CI 1.01–1.11; p = 0.004 and OR:1.008, 95% CI 1.000–1.015; p = 0.034, respectively). The model had a sensitivity of 83%, a specificity of 72%, and positive and negative predictive values of 12% and 99%, respectively. The area under the receiver operating characteristic (AUC-ROC) curve was 0.77 and correctly classified 72% of PE pregnancies. In conclusion, the multivariate classification model developed may be of utility as an aid in identifying pre-symptomatic women who subsequently develop PE.

Reduced cellular glucose transport confers natural protection against dextrose-induced superoxide generation and endoplasmic reticulum stress in domestic hen.

Normal blood glucose levels in avian species are two to fourfold higher than that in humans and the higher blood glucose levels in birds do not cause adverse effects. Endothelial cells isolated from the aorta of the domestic hen (Gallus gallus domesticus) and chicken aortic smooth muscle cells (CAOSMC) were compared to human coronary artery endothelial cells (HCAEC) and human primary aortic smooth muscle cells (HASMC). Superoxide (SO) generation was measured using a superoxide‐reactive probe. ER stress was measured using the placental alkaline phosphatase assay (ES‐TRAP). Glucose transport kinetics were determined using the 3H‐2‐deoxyglucose tracer. Dextrose‐induced SO generation and ER stress were significantly blunted in avian endothelial cells compared to human cells. The Vmax of glucose uptake (in nmoles/mg protein/min) in avian endothelial cells (0.0018 ± 0.0001) and smooth muscle cells (0.0015 ± 0.0007) was approximately 18–25 fold lower compared to the Vmax in HCAEC (0.033 ± 0.0025) and HASMC (0.038 ± 0.004) (all p < 0.0001). The Michaelis–Menten constant (Km) of transport was also significantly different (p < 0.0001) in avian species. The relative resistance of avian cells to dextrose‐induced oxidative stress and ER stress is mostly the result of reduced cellular dextrose transport.

Precise detection of the germinomatous component of intracranial germ cell tumors of the basal ganglia and thalamus using placental alkaline phosphatase in cerebrospinal fluid.

The disadvantages of biopsy for lesions in the basal ganglia and thalamus include a risk of various complications, difficulty in selecting the target tissue in some cases due to indistinct neuroimaging findings and limited availability of sample tissue. Placental alkaline phosphatase (PLAP) plays a decisive role in the diagnosis and management of intracranial germ cell tumors (IGCTs) in the basal ganglia and thalamus. The present study aimed to demonstrate the ability, specificity, and optimal use of PLAP values obtained from cerebrospinal fluid (CSF). Twenty patients with lesions in the basal ganglia and thalamus were enrolled in this study: 11 had IGCTs and 9 had non-IGCTs. The values of PLAP and other established tumor markers in the CSF were measured in all patients before treatment. The mean follow-up period was 76.0months (range, 3-168) for all lesions. PLAP was elevated in all 11 patients with IGCTs in the basal ganglia or thalamus, whereas none of the patients with non-IGCT exhibited elevated PLAP. Thus, the sensitivity and specificity of PLAP were both 100%. Our data demonstrated that the PLAP value can specifically identify the germinomatous component even in cases of IGCTs in the basal ganglia or thalamus with high sensitivity and specificity. PLAP is undoubtedly beneficial for the safe and timely detection of the germinomatous component of IGCTs in the basal ganglia and thalamus, because reliance on PLAP measurement enables us to avoid invasive surgical procedures and facilitates the prompt initiation of chemoradiation therapy.

CONDITION OF FETURES AND NEWBORNS FROM WOMEN WITH INFERTILITY TREATED WITH ASSISTED REPRODUCTIVE TECHNOLOGIES AND WITH CONCOMITANT INTRAHEPATIC CHOLESTASIS

The aim: Improving the effects of pregnancy on the fetus and newborn through early diagnosis and timely comprehensive therapy of pregnant women with intrahepatic cholestasis. Materials and methods: We have conducted a complex examination of 60 women who got pregnant owing to assisted reproductive technologies, with concomitant intrahepatic cholestasis, and 20 practically healthy women with a physiological course of pregnancy and labor (reference group), aged between 18 and 42. The research did not involve pregnant women with chronic liver diseases, viral hepatitis, skin diseases. Womens who underwent the suggested complex drug therapy with Ursofalc, L-arginine and Omega 3, with peroral administration for 14 days according to the following scheme: Ursofalc – 250 mg once a day, L-arginine – 5 ml 3 times a day, Omega 3 – 1 capsule a day. The complex examination of pregnant women with IHC was conducted before and after treatment. We analyzed the data of anamnesis, carried out anthropometric measurements, clinical biochemical examinations of the women with IHC, including the measurement of the levels of alanine aminotransferase, aspartate aminotransferase, total and direct bilirubin, total and placental alkaline phosphatase, leucine aminopeptidase, 5’-nucleotidase, cholic, deoxycholic and chenodeoxycholic acids as wells as their total level. Results: Almost 40 % of women with intrahepatic cholestasis gave birth to babies with asphyxia, including severe one in 11.1 % of cases, 1/3 of the newborns were premature, 40% had signs of hypotrophy, and 66.7 % experienced a disturbed course of early neonatal adaptation. There was also a higher level of perinatal mortality. The newborns from women who had undergone the suggested complex therapy presented no cases of hypotrophy, prenatal infection or cerebral circulation disorder. Conclusions: Thus, functional hepatic disorders in women with infertility play a certain role in the carrying of pregnancy after ART, in the development of pregnancy complications and adverse consequences for women and their newborns. The conducted research shows that early diagnosis and timely complex therapy of pregnant women with intrahepatic cholestasis makes it possible to influence the pathogenesis of perinatal complications and improve the consequences of pregnancy for the fetus and the newborn.

Central diabetes insipidus developing in a 6-year-old patient 4 years after the remission of unifocal bone Langerhans cell histiocytosis

.A six-year-old boy was referred with a one-and-a-half months history of polyuria and polydipsia. At the age of two, he had a single lytic bone lesion in his femoral head, diagnosed as Langerhans cell histiocytosis (LCH) by biopsy at another hospital. As no other affected organs were detected and the affected bone lesion was self-limited, he was not followed up afterward and was doing well. He was diagnosed with diabetes insipidus (DI) by confirming hypernatremia (Na: 148 mEq/l) with hyperosmolar serum (s-Osm 298 mOSM/kg) and inappropriately diluted urine (u-Osm 205 mOSM/kg). His polyuria and polydipsia improved dramatically using the perioral diuretic hormone, and other pituitary functions were not impaired. Magnetic resonance imaging revealed an enlarged pituitary stalk. Sensitive and specific biomarkers of germ cell tumors, including alpha-fetoprotein, placental alkaline phosphatase, and β-hCG in the cerebrospinal fluid, were not detected, indicating relapse of LCH. Genetic analysis revealed a BRAF V600E mutation in the primary bone lesion. We recommend systematic follow-up of patients with a history of LCH, even non-CNS single-system single-site disease, especially with BRAF V600E mutation.

Extragonadal Mixed Germ Cell Tumor Presenting as Large Mass in the Pelvic Cavity

Extragonadal germ cell tumors are relatively rare tumor, which usually occurs in the mediastinum or retroperitoneum. In this report, we present a case of primary mixed germ cell tumor (GCT) arising in the pelvic cavity. A 38-year-old male with acute abdominal pain was admitted to our hospital. Computed tomography scan imaging demonstrated a large mass in the pelvic cavity. Histological examination of the specimen revealed germ cell tumor with dual morphology. Immunohistochemical studies detected placental alkaline phosphatase (ALP), OCT3/4, ALP, and pancytokeratin. Taking these results together with the patient's other clinical manifestations, this case was diagnosed with mixed GCT, i.e., seminoma plus yolk sac tumor. Chemotherapy was successful. Mixed germ cell tumor in the pelvic cavity is extremely rare but should be considered as a cause of pelvic mass formation.