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Background: clarithromycin is a semisynthetic macrolide antibiotic, exhibits broad-spectrum activity against gram-positive and gram-negative aerobes. Macrolides are bacteriostatic antibiotics that inhibit protein biosynthesis via reversible binding to the bacterial 50S ribosomal subunit. Macrolides are able to cross placenta and reach the fetus. Aim of the work: the present study is focused on evaluating the effects of antimicrobial drug, clarithromycin on the kidneys of pregnant rats. Material and methods: clarithromycin is orally given to the treated groups of the pregnant rats once daily at different periods of gestation by gastric tube at a dose of 45 mg/kg/day. The excised kidneys were dissected, processed and stained with H & E, PAS, Masson's trichrome, Feulgen reaction and anti-CD68 immunohistochemical stain then followed by morphometric measurements and statistical analysis. The kidneys were also preserved for DNA fragmentation assay. Results: this study revealed that clarithromycin administration especially to pregnant rats showed different histopathological and histochemical changes in kidney tissues and cellular DNA. Also immunohistochemical anti-inflammatory marker CD68 showed positive reactivity in all treated groups. Conclusion: The presence of histopathological and histochemical changes revealed nephrotoxicity in the pregnant rats after administration of the antimicrobial drug, clarithromycin. [ABSTRACT FROM AUTHOR]

Introduction: oral contraceptive pills (OCPs) are the most popular form of hormonal contraception in young women. Aim of the work: the present study focused on evaluating the effects of two different contraceptive pills including combined pills (estrogen and progesterone) and mini pills (progesterone only) on the cervix of female rabbit. Material and methods: after three months of daily oral administration of these contraceptive pills the animals were sacrificed. The excised organs were dissected, processed and stained with H & E, PAS reaction and Masson's trichrome stain and orcein stain. This was followed by morphometric measurements and statistical study. Results: this study revealed that contraceptive pills administration - specially the combined one - caused marked alterations in the form of hyperplastic cervical mucosal cells and hypertrophied muscular layer. Also, there was a significant increase in collagenous and elastic fibres content in the muscular layer of the cervix. There was also a statistically significant increase in PAS positive materials in the lumina of the mucosal glands of the cervix. All these changes were less marked in the case of mini pill treatment Conclusion: pills of progesterone only showed marked histopathological change, in the cervix as a contraceptive mean, but in less manner than the combined pills (estrogen and progesterone). [ABSTRACT FROM AUTHOR]

Background: Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Escherichia coli infection. E. coli has been epidemiologically linked to urothelial carcinoma of the urinary bladder by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds. Material and methods: After each 3, 6 and 9 months of daily oral administration of dibutyl amine (DBA) plus sodium nitrate (nitrosamine precursors) in drinking water, curcuma in grinding diet and bladder injection with E. coli, rats were sacrificed. The excited bladder were dissected, processed and stained with H&E and anti-Ki67 immunohistochemical stains. This was followed by Elisa for caspse-3 and statistical analysis. Results: The current results indicated that E. coli infection in the bladder tissues increases the carcinogenic ability of nitrosamine precursors through caused marked alteration in the form hyperplastic, dysplastic and metaplastic urothelium. Also, there was a statistically significant increase in ki67 immunoreactivity in urothelium. However, a statistically significant decrease in the concentration of caspase-3 in bladder tissue consequently caused the process of carcinogenesis. All these changes were less marked after curcuma treatment when compared with the group that not treated with curcuma. Conclusion: Bacterial infection of the urinary bladder may play a major additive and possible role in bladder carcinogenesis. Rhizome of curcuma may have a protective action during induction of urinary bladder tumors. [ABSTRACT FROM AUTHOR]

Abstract Background Carbohydrates embedded in the plasma membrane are one of the main actors involved in the communication of cells with the microenvironment. Neuraminic sialic acids are glycocalyx sugars that play important roles in the modulation of malignant cell behaviour. N-glycolylneuraminic acid (NeuGc) is synthesized by the cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH), an enzyme expressed in all mammals except humans. In mice, this sugar is synthesized in several somatic tissues. Methods We used the B16 melanoma and F3II mammary carcinoma mouse tumor cell lines. By CMAH directed RT-PCR and NeuGc detection with the specific anti-NeuGc-GM3 antibody 14F7 we evaluated enzyme and ganglioside expression in tumor cells, respectively. Expression of NeuGc-GM3 ganglioside was reached by in vitro incubation with NeuGc-rich bovine submaxillary mucin and evaluated by slot-blot and immunohistochemistry assays using the 14F7 antibody. Tumor cells treated with mucin or purified NeuGc were injected s.c. and i.v. in syngeneic mice to evaluate tumor and metastatic growth. Results In the present work we demonstrated the absence of expression of CMAH enzyme in B16 melanoma and F3II mammary carcinoma cells. In vitro incubation of these NeuGc-negative cells with NeuGc-rich mucin increased the presence of NeuGc in cell membranes for at least 48-72 h, as a component of the GM3 ganglioside. Preincubation with NeuGc-rich mucin reduced tumor latency and increased the metastatic potential of tumor cells in syngeneic animals. Similar results were obtained when cells were incubated with purified NeuGc alone. Conclusion Our results indicate that B16 and F3II mouse tumor cell lines do not express NeuGc in cell membranes but they are able to incorporate NeuGc from an exogenous source, contributing to the malignant phenotype of melanoma and mammary carcinoma cells.

The Coronavirus pandemic outbreak has induced many urgent adaptation measures in Morocco including medical education that had to abruptly adopt an exclusive distant education approach, without former sufficient preparation. The present study aimed to assess medical students' engagement in their acutely implemented distant learning and to identify factors that could be associated to the students' studying engagement levels. Medical students from 1st to 5th years of medical studies, enrolled in all Moroccan public medical faculties were invited to fill-in an anonymous online questionnaire. 3174 medical students took part in the study, with a mean age of 20.4 +/- 1.8 years old, and 65.4% of them were women. 90% of the participants reported moderate to drastic change of their sleeping habits and 65% suffered depression symptoms. 20.7% of students didn't engage at all in their learning, 26% studied for less than one hour daily, and only 53.3% studied for one hour or more daily. Only 46.4% of the participants had access to multimedia studying resources and only 20.9% were offered online interactive sessions with their teachers. 41.8% of the participants were unsatisfied from their distant learning experience. Lower studying engagement rates were significantly associated with older age, male gender, change of sleeping patterns, depression symptoms, and also with lack of access to multimedia studying resources and poor general satisfaction from the distant learning experience. Distant Education needs to include more interactive activities and more multimedia studying resources to engage students more efficiently in their self-regulated learning., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Introduction: The identification of molecules expressed selectively on the surface of retinoblastoma cells would allow applying targeted therapies. The Ganglioside, N-Glycolyl-GM3 (NeuGc-GM3), is an attractive candidate, as it has been detected in other paediatric neuroectodermic tumours, and it is not expressed in human normal tissues. The 14F7 antibody recognizes specifically the ganglioside NeuGc-GM3., Purpose: To characterize the expression of NeuGc-GM3 in retinoblastoma cell lines and in retinoblastoma tumours using the 14F7 monoclonal antibody., Methods: We studied WERI-Rb1 and Y79 cell lines, 24 retinoblastoma primary tumours from unilateral and bilateral cases and two bone marrow biopsies from metastatic retinoblastoma. Tumours were classified into three groups: non-invasive (n = 13), invasive (n = 9) and metastatic (n = 2). Three eyes enucleated because of non-tumoural conditions were used as controls. Cell lines and tumour sections were studied by immunohistochemistry using the 14F7 antibody. NeuGc-GM3 expression was evaluated by analysing the percentage of positive tumoural cells and the staining intensity. These parameters were analysed comparatively among the three groups., Results: Both retinoblastoma cell lines showed immunoreactivity to NeuGc-GM3 but WERI-Rb1 presented higher intensity than Y79. All the tumours studied showed strong immunoreactivity to NeuGc-GM3 with no significant differences among groups. In both bone marrow specimens, NeuGc-GM3 immunoreactivity was observed in retinoblastoma cells. In bilaterally enucleated cases, NeuGc-GM3 immunoreactivity was not altered before and after chemotherapy. Non-tumoural retinas were negative., Conclusions: NeuGc-GM3 is highly expressed in retinoblastoma cell lines, tumours and metastatic cells to the bone marrow, and it is not detectable in control eyes. There were no significant differences in the immunoreactivity to 14F7 among tumours from different disease stages. Its immunoreactivity did not change after chemotherapy., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aim: To evaluate minimally disseminated disease (MDD) in cytologically negative cerebrospinal fluid (CSF) specimens of patients with high-risk retinoblastoma by the detection of the synthase of ganglioside GD2 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR)., Methods: The CSF was evaluated in 26 patients with high risk for CSF relapse: 14 with postlaminar optic nerve invasion, five of them with tumour at the resection margin, five with massive choroidal invasion, three with overt orbital extension and four patients with systemic metastasis. Serial CSF examinations were repeated at different time intervals according to stage and in the event of suspected relapse. GD2 synthase mRNA was evaluated by RT and nested PCR at each procedure., Results: MDD was present at diagnosis in six cases (23%) and it was significantly associated to massive optic nerve involvement or history of glaucoma (p<0.05). Three of the children with positive MDD had a CSF relapse. Thirteen patients had negative MDD at diagnosis and one had a CSF relapse. In seven children no ARN could be obtained for PCR analysis and two subsequently relapsed. The probability of CSF relapse was 0.50 (95% confidence interval (CI) 0.13-0.88) for children with MDD and 0.08 (95% CI 0.02-0.46) for those with negative RT-PCR examination of the CSF at diagnosis (p=0.03)., Conclusions: MDD in the CSF detected by RT-PCR for GD2-synthase mRNA occurred in 31.7% of evaluable high-risk children with retinoblastoma with no initial central nervous system (CNS) involvement. It was significantly associated to optic nerve involvement and glaucoma and increased risk of CSF relapse., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Tissue factor (TF) is a molecular marker that is up-regulated in cancer cells and aids tumoral dissemination. Our purpose was to develop a nested RT-PCR strategy against TF for detecting blood-borne tumour cells. Our method detected TF expression in a minimum of 1.5 pg total RNA from MCF7 cells. A preliminary study in blood samples from 16 advanced breast carcinoma patients showed that 80% of patients with high TF load progressed and died, while only 18% with low TF load showed the same behaviour. Kaplan-Meier analysis confirmed worse overall survival in patients with high TF load.

Purpose: A heterophilic ganglioside cancer vaccine was developed by combining NeuGcGM3 with the outer membrane protein complex of Neisseria meningitidis to form very small size proteoliposomes (VSSP). A phase I clinical trial was performed to determine safety and immunogenicity of this vaccine., Patients and Methods: Stage III to IV breast cancer patients received up to 15 (200 micro g) doses of the vaccine by intramuscular injection. The first five doses (induction phase) were given at 2-week intervals, with the remaining treatment (maintenance) administered on a monthly basis., Results: Twenty-one patients, 11 of whom had metastatic disease, were included. Main toxicities included erythema and induration at the injection site, sometimes associated with mild pain, and low-grade fever (World Health Organization grades 1 and 2). All treated patients who completed the induction phase developed anti-NeuGcGM3 antibody titers between 1:1,280 and 1:164,000 immunoglobulin G (IgG), and 1:640 and 1:164,000 IgM. Noteworthy specific IgA antibodies were induced by vaccination in all stage III patients and in three stage IV patients. Serum antibody levels were higher in the stage III patients, with the larger increases observed after week 32. The antiganglioside IgG subclasses were mainly IgG1 and IgG3. Hyperimmune sera increased complement-mediated cytotoxicity versus P3X63 myeloma cells and a marked IgG differential reactivity against human mammary ductal carcinoma samples., Conclusion: NeuGcGM3/VSSP/Montanide ISA 51 is an unusual immunogenic ganglioside vaccine and also seems to be safe in this small trial. Immunologic surrogates of activity indicate that this reagent warrants further investigation.

We have examined the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in tumor-bearing BALB/c mice using the syngeneic F3II mammary carcinoma. In the present model, progression of subcutaneous tumors induced massive myelopoiesis in bone marrow and spleen due to GM-CSF secretion by tumor cells. In vitro, the addition of recombinant mouse GM-CSF (5- 25 ng/ml) caused a significant increase in F3II cell growth, either in the presence or absence of serum. Zymographic analysis of conditioned media from F3II monolayers showed that GM-CSF exerted a dose-dependent enhancement in the metalloproteinases MMP-9 (105 kD) and MMP-2 (70 kD), key enzymes in mammary tumor cell invasion. Our data suggest that ectopic GM-CSF production stimulates myelopoiesis and may also play an important role in tumor progression and metastasis formation., (Copyright 2000 S. Karger AG, Basel.)

Lovastatin, a fungal antibiotic used in the treatment of hypercholesterolemia, is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme in the mevalonate pathway of cholesterol synthesis. We examined the antitumor properties of lovastatin on the F3II sarcomatoid mammary carcinoma, a highly invasive and metastatic murine tumor model. Female BALB/c inbred mice were inoculated subcutaneously with F3II tumor cells and injected i.p. daily with 10 mg/kg body weight of lovastatin or administered p.o. at a level corresponding to the human dosage of 1-2 mg/kg/day. Treatment significantly prolonged tumor latency and reduced tumor formation and metastatic dissemination to the lungs from established mammary tumors. In vitro, antitumor properties of lovastatin were strongly associated with inhibition of tumor cell attachment and migration. These actions were prevented by addition of mevalonate but not by equivalent concentrations of farnesyl pyrophosphate. In accordance, Western blot assays showed that lovastatin effects did not appear to be related to modifications in Ras oncoproteins in our model. The present data indicate that lovastatin could be an antitumor agent with potentially useful clinical applications in breast cancer.

The few and small renal corpuscles of the lizard Podarcis (= Lacerta) taurica are composed of a tuft of three to four capillaries (glomerulus), Bowman's capsule and mesangium. The thin interdigitated capillary endothelial cells are, in most regions, in contact with the mesangium. In some regions, however, they rest on a bilaminate basement membrane with an electron-dense lamina densa and a less dense lamina rara. Bowman's capsule is composed of visceral and parietal layers. The epithelial cells (podocytes) of the visceral layer bear trabeculae connected to pedicels with microvilli. The pedicels rest on a bilaminate basement membrane which in some regions has a double-layered densa with connecting bands. Generally, this basement membrane is thicker than that of the capillary endothelial cells. The mesangium is composed mostly of irregular satellite cells with large nuclei and cytoplasmic processes, but also has smaller cells with kidney-shaped nuclei and cytoplasmic processes containing microfilaments. The mesangium cells are embedded in a collagenous matrix which extends to invade the area between the epithelial basement membrane and the capillary endothelium. These observations are discussed in relation to the structure and function of vertebrate renal corpuscles with special reference to the mesangium.