Mast cells play a central role in the genesis and modulation of allergic and inflammatory responses. The general aim of the present work was to study the interaction between mast cells and the most common additives approved for use in foods. Dose-response studies about the effect of the main food additives (tartrazine, sodium bisulphite and sodium benzoate) on mast cell degranulation were carried out. Rat peritoneal mast cells were incubated with: 1) buffer solution or 2) stimulus. The stimuli were tartrazine, sodium benzoate, sodium bisulphite and the calcium ionophore A23187. A23187 was used as a reference mast cell secretagogue. Different doses and combinations of food additives were used. The viability of the mast cells was evaluated with trypan blue. In the incubation solutions, the release of β-hexosaminidase was quantified by colorimetric reaction and ELISA plate reader. The remaining β-hexosaminidase concentration (not released) was studied in the cells after the incubations, and morphology of the mast cells was analyzed by light microscopy with toluidine blue stain. The food additives tartrazine, sodium benzoate and sodium bisulphite did not stimulate the release of β-hexosaminidase from mast cells at any of the concentrations used. In contrast, tartrazine at concentrations of 0.1 μM and 1 μM, and sodium benzoate and sodium bisulphite at concentrations of 0.1 μM, 1 μM, 10 μM and 100 μM, significantly inhibited the basal release of β-hexosaminidase from mast cells. Considering these findings, we decided to determine the effect of these additives on the degranulation of mast cells induced by the calcium ionophore A23187. Sodium bisulphite inhibited mast cell activation induced by the calcium ionophore A23187 in this experimental model. The present study demonstrates that food additives of usual permitted use do not stimulate basal degranulation of mast cells in an in vitro model of peritoneal mast cells and that the additive sodium bisulphite inhibit mast cell activation induced by intracellular calcium increase. This food additive could represent an interesting alternative in the prevention of pathologies mediated by mast cells, as well as in the field of nutritional biochemistry.
Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono-or bi-substituted/crosslinked adducts) or -OH groups (to form ester linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological and pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, and Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, supranuclear palsy, Huntington’s disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. Here we describe the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.
Inflammation is a complex biological reaction induced by the alteration of tissue homeostasis, which occurs in response to the presence of a biological, chemical or physical agent in the body [1]. The acute inflammatory response is composed of an elaborate cascade of both proinflammatory and anti-inflammatory mediators, and balance between these mediators often determines the outcome after injury [2]. Generally during acute inflammation, cellular and molecular events and interactions reduce the risk of eventual injuries or infections. However, acute inflammation can become chronic, contributing to a variety of chronic inflammatory diseases [3]. Major micro circulatory events that occur during the inflammatory process include changes in vascular permeability, leukocyte recruitment and accumulation, and inflammatory mediator’s release [4].
The Positive Regulatory Domain (PRDM) protein family gene is involved in a spectrum variety of biological processes, including proliferation, differentiation and apoptosis: its member seem to be transcriptional regulators highly cell type and tissue peculiar, towards histones modifications or recruitment of specific interaction patters to modify the expression of target genes. In this study we analyzed the expression profile of different member of PRDM gene family focusing our attention on the role of PRDM2, PRDM4 and PRDM10 genes in mouse C2C12 cell line, during the differentiation of myoblasts into myotubes and speculate about the role of the protein Retinoblastoma protein-interacting zinc finger protein 1-RIZ1, coded by PRDM2 gene, as a regulator of the proliferation/differentiation switch.
Results showed a reduction of PRDM2, PRDM4 and PRDM10 expression level during the commitment of the differentiation of myoblasts into myotubes. The RIZ1 silencing stimulated myoblasts differentiation, similar to the effect of serum deprivation on these cells, associated with an increase of Myogenin expression level, which is considered to be involved in the differentiation of myoblasts into multinucleated myotubes. As demonstrated by chromatin immunoprecipitation experiments, RIZ1 is associated with Myogenin promoter in proliferation condition and after 24h from differentiation induction, negatively controlling therefore Myogenin expression. Moreover RIZ1 silencing induced a reduction in PRDM4 and PRDM10 expression levels leaving us to speculate that the PRDM genes have a redundant role and they are hierarchically organized.
The normal levels of thyroid hormones (THs; thyroxine, T4 & 3,5,3′-triiodo-L-thyronine, T3) are necessary for the normal development [1-48], particularly the fetal and neonatal cardiac growth and development [49]. The actions of THs are facilitated genomically by thyroid receptors (TRs, α and β) and non-genomically at the plasma membrane, in the cytoplasm and in cellular organelles [4,49-55], by stimulation of Na+, K+, Ca2+ and glucose transport, activation of protein kinase C (PKC), protein kinase A (PKA) and mitogen activated and protein kinase (ERK/MAPK) [4]. In addition, the transport of T4 and T3 in and out of cells is controlled by several classes of transmembrane TH-transporters (THTs) [56], including members of the organic anion transporter family (OATP), L-type amino acid transporters (LATs), Na+/Taurocholate cotransporting polypeptide (NTCP), and monocarboxylate transporters (MCTs) [4,49,57,58]. Adding additional complexity, the metabolism of T4 and T3 is regulated by 3 selenoenzyme iodothyronine deiodinases (Ds: D1, D2 and D3) [59-61]. On the other hand, the congenital hypothyroidism can cause the following [49,62-64], (1) congenital heart diseases; (2) diastolic hypertension; (3) reduced cardiac output, stroke volume and a narrow pulse pressure; (4) dilatation and overt heart failure; (5) elevation in the systemic vascular resistance [65-68]. Similarly, the chronic hyperthyroidism can cause the following [49,64]: (1) cardiac hypertrophy; (2) increase in the cardiomyocyte (CM) length rather than width; (3) noticeable diminution in systemic vascular resistance; (4) elevation in the cardiac contractility; (5) systolic hypertension; (6) increase in the cardiac output, venous volume return, blood volume and pulse pressure; and (7) reduction in the systemic vascular resistance [49,69]. T3-therapy can induce DNA synthesis and cardiomyocyte proliferation, and improve the cardiac contractility; though, this action is as still unidentified [49,70-74].
According to literature, about 90% of death from cancer is related to metastasis. Metastatic process present many similarity to some other biological processes. Once we have examined some relevant biomedical literature, by understanding the real causes of metastasis, it would become much more possible to introduce new therapeutic strategies to delay or in some cases even to stop this kind of killer process. Breast cancer, as an example, produces metastasis to different organs, which seems to be related to the subtype. We believe that a deep understanding of the roles of breast cancer cells and their interactions with the liver microenvironment in early breast cancer metastasis could be a crucial factor for the design and development of effective BCLM breast cancer liver metastases therapeutic strategies and to better understand the general process. Let’s suppose the secondary organ or organs can be considered as incubator/s for the primary metastatic cells. What kind of consequences we can have in therapy field if there is an active regulating role in determining the location of secondary cancers?
Let’s observe the role played by liver, bone marrow, CNS central nervous system, lungs, lymphocytes and other secondary locations/organs a little bit closer or maybe from a different angle let’s suppose we try to come up with just a hypothesis. Just let’s take this as a possibility, and we take the thread to see where it takes us.
Synthetic biology is an interdisciplinary branch of biology and engineering. The subject combines various disciplines from within these domains, such as biotechnology, evolutionary biology, molecular biology, systems biology, biophysics, computer engineering, and genetic engineering. Synthetic biology aims to understand whole biological systems working as a unit, rather than investigating their individual components and design new genome. Significant advances have been made using systems biology and synthetic biology approaches, especially in the field of bacterial and eukaryotic cells. Similarly, progress is being made with ‘synthetic approaches’ in genetics and animal sciences, providing exciting opportunities to modulate, genome design and finally synthesis animal for favorite traits.
Background: Cyclophosphamide is used for the treatment of malignant and non-malignant diseases, but, it induces oxidative damage and disturbance in the antioxidant defense system. Zinc oxide nanoparticles (ZnO NPs) are used in biomedical applications and consumer products. ZnO-NPs are protected cell membranes against oxidative damage, decrease free radicals and malondialdehyde (MDA) levels, and increase the antioxidant enzyme levels.
Objectives: The present aimed to evaluate the ameliorative effect of Zn-O nano-particles on oxidative damage and disturbance in the antioxidant defense system induced by cyclophosphamide in male albino rats.
Materials and Methods: 24 adult male albino rats were randomly divided into 4 groups (6 rats of each). Group I (Control group): Received 0.2 ml saline /day i.p. injection for 14 days (day by day), group II, (nZnO group): Received nZnO (5 mg/kg/day) b.w., intraperitoneally for 14 days, Group III (CP group): Received CP (20 mg/kg/day) b.w, day by day for 14 days by intraperitoneal injection, Group IV (CP + ZnO NPs group): Received nZnO group: Received nZnO (5 mg/kg/day) b.w., intraperitoneally for 14 days, plus CP (20 mg/kg/day) b.w., day by day for 14 days by intraperitoneal injection. After 24-hr from the last treatment, all animals were anesthetized using light ether. Blood, lungs, and liver samples were taken and prepared for biochemical measurements.
Results: Individual treatment of zinc oxide nanoparticles and CP induced liver cytochrome b5, cytochrome C reductase, and glutathione S-transferase (GST) compared to the control group, while CP increased P450. The combination of nZnO and CP prevents the elevation of cytochrome b5, P450, cytochrome C reductase, and GST compared with the CP treated group. Zinc oxide nanoparticles and CP increased liver thiobarbituric acid reactive substances (TBARS). The combination of nZnO and CP prevents the changes in TBARS concentrations compared with the CP. Injection of CP to rats reduced the activities of serum glutathione reductase (GR) and catalase (CAT) as compared with the control group. However, combination treatment of rats with nZnO and CP increased the activities of these enzymes compared with those treated with CP alone. Zinc oxide nanoparticles and CP increased serum and lung TBARS, while decreased glutathione (GSH) concentration compared to the control group, with more pronounced changes by CP. The combination of nZnO and CP prevents the changes in TBARS and GSH concentrations compared with the CP.
Conclusion: It can be concluded that CP induced oxidative stress and disturbance in the antioxidant defense system. Treatment of rats with zinc oxide nano-particles and CP together attenuated the oxidative damage and disturbance in the antioxidant defense system induced by CP. So, Patients treated with CP advised to take nZnO to prevent the side effects of chemotherapy. Further studies are necessary to evaluate the amelioration effect nZnO and other nano-particles against oxidative stress induced by CP in different doses and experimental models.
Related the extremely transmittable abilities of SARS-CoV-2,a harmonious virus to the bat CoV, gets transmitted by three principal processes-- the inhalation of droplets from the SARS-CoV-2 infected person, contacting to the person, and by the surfaces and materials defiled with the virus. Whereupon bat Coronavirus is mostly like the pandemic causing virus SARS-CoV-2, bats are often deliberated and figured out as a possible primary host although no intermediate has not been defined yet in the wherewithal of transmission. The Spike Glycoprotein plays an important role in the case of penetration with the assistance of the ACE2 receptor and the Receptor Binding Domain. In the human body, infiltrating the nucleic acid into host cells, SARS-CoV-2 attacks one cell and one by one into the whole human body; therefore, infected cases are found symptomatic and asymptomatic considering the immune power. Patients with cardiovascular disease or diabetes proceed with their treatment with ACE2 often; therefore, there might be a high chance of getting infected. Whereas the SARS-CoV-2 infects the blood and then lungs, Antigens improvement can be better in order to avoid high-complicated effects. Currently, no vaccination or no accurate cure and treatment has not been defined. An explanation with analysis on SARS-CoV-2 has been performed from the aspect of virology, immunology and molecular biology. Several relevant figures have been included hereby in order to a better understanding of the very concept.
Noise is widespread in everyday life and can cause both auditory and non-auditory health impacts. Noise-induced hearing loss remains highly prevalent in occupational settings and is now increasingly caused by exposure to social and environmental noise. Incidence of noise-induced hearing loss (NIHL) has been observed to increase substantially in the recent years. Several advances have taken place in past few years for understanding the molecular basis of NIHL. Our understanding of molecular mechanisms implicated in noise-induced hair-cell and nerve damage has significantly increased. Research in the field of genetics is also advancing at a rapid speed, and several genes linked to NIHL have been discovered. This could help in developing preventive and treatment strategies. This review article focuses on the current research and future trends on auditory effects and consequences of noise pollution in humans, stressing the importance of adequate noise prevention and mitigation strategies as a public health measures.
A 32-year-old G4P301LC3 woman presents to the office for a visit, with a 6-day history of vaginal discharge with an unpleasant odor. On speculum examination, the discharge was green in color and frothy in appearance. Is noticed vulvar erythema, edema, and pruritus, also is noted the characteristic erythematous, punctate epithelial papillae or “strawberry” appearance of the cervix. Vaginal pH was 6.2. Diagnosis of Trichomonas vaginalis is made via wet prep microscopic examination of vaginal swabs.But also, for diagnosis help even the exam with the speculum, concretely “strawberry” appearance of the cervix. The diagnosis is confirmed by culture.Trichomoniasis is a sexually transmitted infection [1,2], that caused by trichomonas vaginalis. Trichomonas vaginalis is a unicellular, anaerobic flagellated protozoan, that inhabits the lower genitourinary tracts of women and men, but that can cause vaginitis. Clinical findings of Trichomonas vaginalis include a profuse discharge with an unpleasant odor. The discharge may be yellow, gray, or green in color and may be frothy in appearance. Vaginal pH is in the 6 to 7.Vulvar erythema, edema, and pruritus can also be noted. The characteristic erythematous, punctate epithelial papillae or “strawberry” appearance of the cervix is apparent in only 10% of cases. Symptoms are usually worse immediately after menses because of the transient increase in vaginal pH at that time. Diagnosis of Trichomonas vaginalis is made via wet prep microscopic examination of vaginal swabs. Other, more sensitive tests are available, including nucleic acid probe study and immunochromatographic capillary flow dipstick technology. The diagnosis can be confirmed when necessary with culture, which is the most sensitive and specific study. Nucleic acid amplification tests (NAATs) have replaced culture as the gold standard. T vaginalis NAATs have been validated in asymptomatic and symptomatic women and are a highly sensitive test [3]. Because the Trichomonas vaginalis is a sexually transmitted infection, both partners should be treated to prevent reinfection. The mainstay of treatment for Trichomonas vaginalis infections is metronidazole. Treatment schemes can be:
Non-small cell lung cancer is one of the leading causes of cancer-related mortality worldwide. Despite recent advances in adjuvant treatments, surgical resection is basis of treatment. With the development of minimally invasive surgery in thoracic surgery, surgeons work on minimally invasive surgery for advanced stages of lung cancer, previously considered non-operable at all or previously considered non-operable with minimally invasive surgery approach.
Minimally invasive surgical techniques which are routinely used in the surgical treatment of early-stage lung cancer have started to be treated in more complicated and advanced stages of lung cancer. Bilateral anatomic resections, operations after neoadjuvant chemotherapy, bronchial sleeve lobectomies, double sleeve lobectomies, complementary pneumonectomies, and carinal sleeve resections can be performed by minimally invasive methods. The option of video-assisted surgery should be considered with oncological principles at foreground if patients have acceptable lung and cardiac performance conditions with minimal comorbidities.
This study reviews VATS experience in patients with advanced-stage lung cancer worldwide and discusses potential benefits and limitations of using VATS technology to perform thoracic surgery procedures.
Segmentectomy may be applied to all segments; superior segmentectomies (lower lobe superior segments for both lungs), lingulectomies (two segments forming lingulas of upper left lobe) and basal segmentectomies (segments other than superior segment for both lungs). In lung segment resections; segmentectomy has an equivalent morbidity, recurrence and survival rate compared to lobectomy, in patients with stage I lung cancer, tumors smaller than 2 cm and within the segmental anatomical limits. Segmentectomy also contributes more to preserving lung function and exercise capacity than lobectomy. In tumor resection; especially in patients with advanced age, insufficient performance or insufficient cardiopulmonary reserve, 2 cm in diameter and acceptable segmental margins may be provided.
Limited long-term results show oncological results of robotic approach similar to open and VATS approaches. Robotic approach facilitates surgery with more intuitive movements, greater flexibility and high definition, three-dimensional vision. However, high cost and lack of touch sense are main disadvantages of robotic surgery. New studies are needed to assess quality of life, morbidity, oncological results and cost effectiveness. However, considering development of technology in our age and fact that many surgical robot brands will be released in the near future, it is predicted that disadvantages of robotic surgery will be minimized in the near future.
This article reviews experience of segmentectomy in non-small cell lung cancer and discusses benefits and limitations of robotic segmentectomy.
Anasarca is generalized swelling of the body following accumulation of fluid in the extracellular compartments. It may result from multiple aetiology mainly of renal, hepatic or cardiovascular origin.
The aim of this case report is to highlight the challenges encountered in making diagnosis in a patient with anarsaca.
We report a case of a 34 year old transporter who presented with anasarca. He had clinical features and risk factors suggestive of renal, hepatic and cardiovascular disease. However investigations ruled out renal, hepatic or cardiovascular diseases as the aetiology of the anarsaca. The anarsarca was also noted to be unresponsive to diuretics. The diagnosis of the disease causing the anarsaca was therefore a dilemma.
Xanthogranulomatous cholecystitis is a rare benign inflammatory disease of gallbladder that may be misdiagnosed as carcinoma of the gallbladder intraoperative or in pre-operative imaging. Intramural accumulation of lipid-laden macrophages and acute and chronic inflammatory cells is the hallmark of the disease. The xanthogranulomatous inflammation can be very severe and can spill over to the neighboring structures like liver, bowel and stomach resulting in dense adhesions, abscess formation, perforation, and fistulous communication with adjacent bowel [1-3]. Cholecysto-colic fistula is a rare and late complication of gallstones roughly found 1 in every 1,000 cholecystectomies.
Clinical featuresThe clinical features are variable and non-specific. Patients with cholecysto-colonic fistula often present with symptoms of acute cholecystitis and preoperative diagnostic tools often fail to show the fistula. Hence most cases it is an on table diagnosis.
ManagementTreatment involves closing the fistula and performing an open or laparoscopic cholecystectomy.
Agranulocytosis is one of the common reasons of consultation in hematology. It’s life-threatening because of an infection risk. The metamizole is a drug, known for its potential rare danger of inducing a severe agranulocytosis. However, it remains widely used because of its beneficial effect analgesic and antipyretic. We report in this study, a case of a girl who was 16 years old, referred for severe agranulocytosis, and appeared two weeks after treatment with Novalgin. The clinico-biological symptoms were dominated by Streptococcal septicemia with an infectious pulmonary and digestive focus. The blood cell count confirmed a severe agranulocytosis with total disappearance of neutrophils. Despite broad-spectrum antibiotic therapy and stimulation with hematopoietic growth factor, the clinical evolution was fatal in the short term. What motivates us to add this case to those of the literature in order to remind practitioners about the danger of this drug, and to promote has doubled of vigilance during use.
Purpose: This work is aimed at demonstrating that scraping cytology and scanning electron microscopy can successfully assist in the diagnosis of nontuberculous mycobacteria infection. For this purpose, we report the use of both these techniques in the diagnosis of cornel ulcer in a previously healthy young man.
Methods: Cytological samples were achieved by scraping technique on the mucosa, both sub palpebral and temporal area of the eye tarsal conjunctiva. The obtained sample was affixed to a sanded rectangular slide, stained with the Pappenheim method, washed in bidistilled water, treated in Giemsa solution, washed again and subsequently dried on a hot plate and observed with a microscope at various magnifications.
Results: After a therapy based on a 500 mg clarithromycin tablet administered every 12 hours for 30 days as systemic therapy, a complete recovery of the patient from left eye inflammation was observed and SEM cytology showed that NTM colonies had disappeared.
Conclusion: Conjunctival cytology scraping and SEM technologies can be therefore exploited as new tools in diagnosis and fast identification of these newly discovered mycobacteria. In fact, they have a new way for studying ocular pathology, because of the simple execution and remarkable accuracy in the diagnosis. In fact, this technique allows to gather valuable information about all pathogens expression and the cellular action involved in pathology. As a further plus, this technique provides clinicians with the opportunity to repeat the SEM cytology for monitoring patients during therapy, hence leading to evaluate the efficacy of the pharmaceutical regimen in real time.
Experience with allogeneic hematopoietic stem cell transplantation (HSCT) in mycosis fungoides/Sezary syndrome (MF/SS) is limited to a small number of case reports and case series [1,2]. The advantage of allogeneic HSCT has been indicated in progressive disease in the review of CIBMTR study groups [3]. A consensus is still not available about the intensity and the content of the conditioning regimen due to the rarity of the disease and heterogeneous patient groups.
In the cardiovascular field, tachycardia and increment of catecholamine plasma levels (sympathetic hyperactivity) have been reported by hypertensive patients that use L-type Ca2+ channel blockers (CCBs) since 70´s. Our discovery of the involvement of interaction between the intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP interaction) revealed that this phenomenon (sympathetic hyperactivity) was resulting of increase of transmitter release from sympathetic neurons stimulated by CCBs due to its interference on the Ca2+/cAMP interaction. In the neuroscience field, this discovery has produced new paths for the understanding of the cellular and molecular mechanisms involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer´s and Parkinson’s diseases. In this way, novel journeys for the development of new pharmacological strategies more effective for the treatment of neurodegenerative diseases may be initiated.
Zoon’s vulvitis or plasma cell vulvitis (PCV) is a rare, benign inflammatory condition of the vulvar mucosa [1]. PCV can present with an asymptomatic lesion, or can cause discomfort, dyspareunia and pruritus [2]. In this way, PCV can mimic other lesions of the vulval mucosa, such as lichen planus.
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Dr. Elizabeth A Awoyesuku
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