scholarly journals Role of the N, N′-dimethylbiguanide metformin in the treatment of female prepuberal BALB/c mice hyperandrogenized with dehydroepiandrosterone

Reproduction ◽  
2006 ◽  
Vol 131 (3) ◽  
pp. 591-602 ◽  
Author(s):  
Valeria Sander ◽  
Carolina Griselda Luchetti ◽  
María Emilia Solano ◽  
Evelin Elia ◽  
Guillermo Di Girolamo ◽  
...  
Keyword(s):  
Body Weight ◽  
Lymph Nodes ◽  
T Lymphocyte ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Prostaglandin E ◽  
Lymphocyte Population ◽  
Cd8 T Lymphocyte ◽  
Tnf Α

The present study investigated the role of the N, N{′ }-dimethylbiguanide metformin (50 mg/100 g body weight in 0.05 ml water, given orally with a canulla) in the prevention of endocrine and immune disorders provoked by the hyperandrogenization with dehydroepiandrosterone (DHEA) in prepuberal BALB/c mice. The treatment with DHEA (6 mg/100 g body weight in 0.1 ml oil) for 20 consecutive days, recreates a mouse model that resembles some aspects of the human polycystic ovary syndrome (PCOS). The treatment with DHEA did not modify either body mass index (BMI) or blood glucose levels, but did increase fasting insulin levels when compared with controls. Markers of ovarian function – serum estradiol (E), progesterone (P) and ovarian prostaglandin E (PGE) – were evaluated. The treatment with DHEA increased serum E and P levels while ovarian PGE diminished. When metformin was administered together with DHEA, serum insulin, E and P levels, and ovarian PGE values did not differ when compared with controls. Using flow cytometry assays we found that the treatment with DHEA diminished the percentage of the CD4 + T lymphocyte population and increased the percentage of the CD8 + T lymphocyte population from both ovarian tissue and retroperitoneal lymph nodes. However, when metformin was administered together with DHEA, the percentages of CD4 + and CD8 + T lymphocyte populations from both ovarian tissue and retroperitoneal lymph nodes were similar to those observed in controls. Finally, when DHEA was administered alone it increased the serum tumor necrosis factor-alpha (TNF-α ) levels when compared with controls; however, when metformin was administered together with DHEA, serum TNF-α levels were similar to controls. These results indicate that metformin is able, directly or indirectly, to avoid the endocrine and immune alterations produced when mice are hyperandrogenized with DHEA.

scholarly journals Clinical Outcome Prediction in COVID-19 Patients by Lymphocyte Subsets Analysis and Monocytes’ iTNF-α Expression

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 735
Author(s):  
Gabriele Madonna ◽  
Silvia Sale ◽  
Mariaelena Capone ◽  
Chiara De Falco ◽  
Valentina Santocchio ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Inflammatory Cells ◽  
Retrospective Assessment ◽  
Cd8 T Lymphocytes ◽  
Cd8 T Lymphocyte ◽  
Tnf Α ◽  
Cellular Mediators ◽  
Novel Coronavirus

In December 2019, a novel coronavirus, “SARS-CoV-2”, was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

P–449 Evaluation of ovarian reserve in female children and adolescents with non-iatrogenic primary ovarian insufficiency to establish criteria for ovarian tissue cryopreservation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Volodarsky-Perel ◽  
M Zajicek ◽  
D Shai ◽  
H Raanani ◽  
N Gruber ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Reserve ◽  
Predictive Value ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Antral Follicle ◽  
Ovarian Tissue Cryopreservation ◽  
Positive Parameter ◽  
Primordial Follicles

Abstract Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH > 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable

scholarly journals Essential Role of Platelet-Activating Factor in Control of Leishmania (Leishmania)amazonensis Infection

2000 ◽  
Vol 68 (11) ◽  
pp. 6355-6361 ◽  
Author(s):  
Maria Valdrinez Campana Lonardoni ◽  
Momtchillo Russo ◽  
Sonia Jancar
Keyword(s):  
Lymph Nodes ◽  
Platelet Activating Factor ◽  
Parasite Load ◽  
Peritoneal Macrophages ◽  
Leishmania Infection ◽  
Prostaglandin E ◽  
No Production ◽  
Regional Lymph Nodes

ABSTRACT In the present study we investigated the role of platelet-activating factor (PAF) and prostaglandins in experimental Leishmania (Leishmania)amazonensis infection and the relationship between these mediators and nitric oxide (NO) production. Mouse peritoneal macrophages elicited with thioglicolate were infected with leishmania amastigotes, and the infection index determined 48 h later. The course of infection was monitored for 5 weeks in mice infected in the footpad with promastigotes by measuring the footpad swelling and parasite load in regional lymph nodes and spleen. The addition of PAF to C57BL/6 mouse macrophages significantly inhibited parasite growth and induced NO production. Treatment of macrophages with a selective PAF antagonist, WEB2086, increased the infection, indicating that endogenously produced PAF regulates macrophage ability to control leishmania infection. This effect of PAF was abolished by addition of the inhibitor of NO synthesis, L-NAME, to the cultures. The addition of prostaglandin E2 significantly increased the infection and NO production. Treatment with cyclo-oxygenase inhibitor, indomethacin, reduced the infection and PAF-induced release of NO. Thus, the increased NO production induced by PAF seems to be mediated by prostaglandins. The more-selective inhibitors of cyclo-oxygenase 2, nimesulide and NS-398, had no significant effect. Thus, antileishmanial activity correlates better with the presence of PAF or absence of prostaglandins than with NO production. In vivo treatment with PAF antagonists significantly increased leishmania lesions, as well as the parasite load, in regional lymph nodes and spleens. These findings indicate that PAF is essential for the control of leishmania infection.

CHRONIC REJECTION: ROLE OF CD8+ T LYMPHOCYTE ON MEDIAL SMOOTH MUSCLE CELL.

1999 ◽  
Vol 67 (7) ◽  
pp. S56
Author(s):  
J F Legare ◽  
T Issekutz ◽  
T DG Lee ◽  
G Hirsch
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
T Lymphocyte ◽  
Chronic Rejection ◽  
Cd8 T Lymphocyte

Changes in ovarian hormonal status in cervical cancer patients under the influence of combined HPV/chlamydia trachomatis infection.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17019-e17019
Author(s):  
Valeria Bandovkina ◽  
Elena Mikhaylovna Frantsiyants ◽  
Nailya Guskova ◽  
Tatiana Moiseenko ◽  
Marina Vovkochina ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Chlamydia Trachomatis ◽  
Cancer Patients ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Sharp Decrease ◽  
Chlamydia Trachomatis Infection ◽  
Endocrine Status ◽  
Steroid Binding

e17019 Background: The purpose of the study was to analyze hormonal disorders in tissues of histologically unchanged ovaries of patients with cervical cancer infected with HPV/Chlamydia trachomatis. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4), steroid-binding globulin (SBG) and prolactin (PRL) by the ELISA in intact ovaries of 25 patients aged 53.4±3.2 years with cervical cancer T1b-2aN0M0. HPV presence was determined by Е7 protein expression, Chlamydia trachomatis (Ch. tr.) – by IgG and IgА to Ch. tr. and antigen/DNA by ELISA and Real-time PCR. Tissues of intact ovaries obtained during hysterectomy from 22 non-infected women of similar age with endometrial cancer T1N0M0 were used as the control. Results: The data demonstrated a sharp decrease in E2 level by 9.3 times and increase in E1 by 2.3 times in intact ovaries of cervical cancer patients infected with HPV and Ch. tr., compared with the values in controls. Changes were noted in the balance between some estrogen fractions: E1 percentage increased by 5 times, E3 – by 2.4 times and E2 percentage decreased by 4 times. Androgenic status in intact ovaries in cervical cancer was characterized with increased levels of T (by 5.1 times) and fT (by 1.6 times). We noted an increase in SBG concentration by more than 3 times in response to the release of androgens registered in ovarian tissue, as well as significant (by 4.4 times) increase in PRL and decrease in P4 by 1.5 times compared with non-infected tissues. Estrogens to P4 ratio in co-infected patients reduced by 1.6 times, while the PRL to P4 ratio increased by 6.4 times, mainly due to disorders in hormone-producing ovarian function. Conclusions: The development of malignant process in the cervix in a combined HPV and Chlamydia trachomatis infection is accompanied by disorders of the endocrine status in tissues of intact ovaries and shows the undeniable role of consequences of HPV/Chlamydia trachomatis coinfection in this process.

scholarly journals AMELIORATIVE ROLE OF SILYMARIN AGAINST ASPARTAME–INDUCED BIOCHEMICAL CHANGES, OXIDATIVE STRESS, INFLAMMATORY EFFECT AND GENOTOXICITY IN MALE ALBINO RATS

2020 ◽  
pp. 41-55
Author(s):  
SABHA E. ELBALLAT ◽  
AL-SHIMAA M. ABAS
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
World Health ◽  
Control Group ◽  
Albino Rats ◽  
Antioxidative Status ◽  
Tnf Α ◽  
Recovery Group ◽  
Different Tissues

Objective: Aspartame (ASP) is one of the most common artificial sweeteners. It has been recorded to be safe by World Health Organization. However, numerous publications have concluded that ASP is a genotoxic and carcinogenic sweetener. Methods: The current study aims to examine the effect of ASP consumption (250 mg/kg body weight/day for 90 d) on some biochemical parameters, oxidative/antioxidative status in different tissues, Tumor Necrosis Factor-α (TNF-α), chromosomal aberration (CA) frequency and mitotic index (MI) percentage in addition to the possible ameliorative role of silymarin (50 mg/kg body weight/day for 90 d) against ASP-induced toxicity in male albino rats. Results: The present results have confirmed that ASP is able to induce significant increase in the blood glucose level, liver, kidney and lipid function tests, Malondialdehyde (MDA) level, serum TNF-α level, frequency of CA and MI%. Meanwhile, Glutathione reduced level (GSH), Glutathione–S-transferase (GST) and catalase activity (CAT) were decreased by ASPadministration. Recovery group showed slight enhancement in all parameters but remained significant as compared to the control group. Co-administration of ASP with silymarin showed greater improvement than the recovery group. Conclusion: Silymarin have an ameliorative role against biochemical oxidative stress, inflammatory changes in blood and different tissues, chromosomal aberrations and MI% induced by ASP administration.

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