Chondrogenic re-differentiation potential of chondrocytes after monolayer culture: Comparison between osteoarthritis and young adult patients
Published on: 27th March, 2019
OCLC Number/Unique Identifier: 8049578277
Purpose: Monolayer passage of chondrocytes results in dramatic phenotypic changes. This “de-differentiation” is expected to restore the chondrogenic properties such as “re-differentiation” in autologous chondrocyte implantation (ACI). The purpose of this study was to compare the chondrogenic re-differentiation potential of chondrocytes, from osteoarthritis (OA) patients and young adult patients, after monolayer culture.
Methods: Chondrocytes from five old patients with knee OA (OAC) and five young patients with recurrent shoulder dislocation (non-OAC) were used. The chondrocytes from passages 1 to 3 were analyzed for the expression of cell surface markers (CD73, CD90, CD105, and CD44) by flow cytometric analysis. Chondrocytes of passage 4 were cultured as pellets for re-differentiation and evaluated histologically. Real-time PCR were performed to measure the chondrogenic related genes transcriptional levels.
Results: OAC and non-OAC had comparable positive ratios for CD44, CD73, CD90, and CD105. The expression of CD105 was upregulated from passage 1 to passage 3 in OAC, and it increased at the same level as in non-OAC during passage 2 and 3. The expression of COL2 decreased from passage 1 to passage 3 in both the groups. There were no statistical differences in the Bern Scores between OAC and non-OAC.
Conclusion: The chondrocytes from OA patients and young adult patients had chondrogenic re-differentiation potential. The changes in cell surface markers and chondrogenic related genes showed similarity for both the groups. Our findings suggest that OAC can become the cell source for ACI.
Concentration Polarization of Ox-LDL and Its Effect on Cell Proliferation and Apoptosis in Human Endothelial Cells
Published on: 30th December, 2016
OCLC Number/Unique Identifier: 7286351432
Background: Flow-dependent concentration polarization of native LDL is important in the localization of atherogenesis. However, ox-LDL plays a more important role than n-LDL in atherogenesis by inducing cell proliferation and apoptosis. We hypothesized that concentration polarization of ox-LDL may adversely affect vascular beds due to its toxicity to endothelial cell (EC) lining.
Methods: Using a parallel-plate flow chamber technique, we studied water filtration rate and wall concentration of ox-LDLs EC monolayers cultured on permeable or non-permeable membranes. ECs cultured on permeable and non-permeable membranes were examined in terms of cell viability, ox-LDL uptake, LOX-1 expression and cell apoptosis (Cytochrome c and Bcl-2 expression). We observed that the wall concentration of ox-LDL was about 16% higher in the permeable group than in the permeable group (P<0.05). Cell proliferation (MTT assay) increased in response to low concentration of ox-LDL (1-5 μg/ml), and fell drastically in response to higher concentration; all these changes were more pronounced in the permeable group than in the non-permeable group. The uptake of ox-LDL and LOX-1 expression by ECs were also significantly higher in the permeable group than in the non-permeable group of cultured cells.
Conclusions: These observations suggest that concentration polarization of ox-LDL occurs in an artery that is permeable to water, and ox-LDL concentration polarization can enhance ox-LDL accumulation into the arterial wall and accelerate EC proliferation at low concentrations and apoptosis at high concentrations, possibly via LOX-1 expression.
Short and Medium-Term Evaluation of Patients in Coronary Post-Angioplasty: Préliminary results at the Cardiology Department of the Hospital University Aristide Le Dantec of Dakar (Senegal): Study on 38 Cases
Published on: 20th February, 2017
OCLC Number/Unique Identifier: 7286354250
Introduction: Coronary angioplasty is a safe therapeutic method for coronary disease. However, its major obstacles remain the occurrence of stent thrombosis (ST) and in-stent restenosis (ISR). The aim of this study was to evaluate the short-term and medium-term results of coronary angioplasty patients in the cardiology department of Aristide Le Dantec hospital in Dakar.
Methodology: It was a longitudinal, descriptive and analytical study over a period of 12 months (April 2014 to April 2015) with a follow-up at 6 months. Was included any patient who had a coronary angioplasty with stent placement.
Results: Thirty-eight patients had been included with a male predominance and a sex ratio of 5.32. The average age was 57.94 years. Cardiovascular risk factors were mainly smoking (57.9%) and coronary heredity (42.1%), followed by hypertension (39.5%) and diabete (34.2%). The indications for angioplasty were acute coronary syndromes TS(+) and TS(-) respectively (50%) and (23.7%) and stable angina (26.3%). The right femoral approach was almost exclusive (97.4%). Coronary angiography revealed a predominance of anterior interventricular affection (84.2%). Type B lesions were the most frequent (68.4%). The single-truncal valve affection was predominant (76.3%). Direct stenting accounted for 63.2% of procedures. Twenty-one bare stents (55.3%) and 17 active stents (44.7%) were implanted. The results were excellent (94.7%). One case of acute stent thrombosis was noted. Echocardiography of dobutamine stress during follow-up was positive in 04 patients (12.5%). The control coronary angiography performed in two patients revealed an ISR. The predictive factors for restenosis were dominated by a deterioration in the segmental kinetics (p=0.009), in the diastolic function (p=0.002), the systolic function (p=0.003), a high post angioplasty troponin (p=0.004), the presence of calcifications (p=0.004) and a high SYNTAX score (p=0.021).
Conclusion: According to these results, Angioplasty is an effective therapy for coronary disease. However, a correct intake of double platelet antiaggregants and clinical and non-invasive screening are required for follow-up to avoid stent thrombosis or restenosis.
Subacute infectious endocarditis-associated membranoproliferative glomerular nephritis: A Case Report and Review
Published on: 17th August, 2017
OCLC Number/Unique Identifier: 7286354493
We experienced a case of membranoproliferative glomerulonephritis (MPGN) caused by subacute infectious endocarditis (SIE). A 57-year-old male farmer complained of fatigue, lack of appetite and gross haematuria for a month; he had no cough, chest pain, or exertion dyspnea. After admission, lab tests showed mild proteinuria(1.04g/d) and heavy dysmorphic red blood cells(RBC) (543/HP), with serum creatinine(Scr) slightly elevated(1.46mg/dl) and anemia(hemoglobin Hb 85g/L). A renal biopsy revealed MPGN lesion with 16.6% cellular crescents. The echocardiogram test revealed mitra valve prolapse with perforation of the anterior lobe, vegetation, and severe regurgitation. He was diagnosed as SIE induced MPGN. Then he underwent mitral valve replacement after systemic antibiotic treatment without immunosuppressive agents. Follow-up showed that he dramatically regained normal kidney function in total 1 year after the operation. Thus, antibiotic administration and valve replacement may be efficient enough for some of SIE induced MPGN. We did a brief review of the literature on SIE induced MPGN, which was sometimes misdiagnosed due to its silent characteristics; some SIE patients may initially have other organs involved.
Lipid-induced cardiovascular diseases
Published on: 23rd November, 2017
OCLC Number/Unique Identifier: 7666351562
Cardiovascular diseases are the leading cause of death worldwide. There are many evidences that the dysfunctioning lipotoxicity is the one of major factors of cardiovascular diseases such as, atherosclerosis, hypertension, and coronary heart disease. Obesity and diabetes increase circulating lipids that are likely with more generation of toxic intermediates, which leading to the complications associated with cardiovascular diseases. Indeed, lipotoxicity is a metabolic syndrome caused by abnormal lipid accumulation, which leads to cellular dysfunction and necrosis. Here we review the factors that induced pathogenesis of cardiovascular diseases by lipid accumulation and the mechanisms underlying the lipotoxicity.
Hyperkalemia: An archenemy in emergency medicine. Description of two case reports
Published on: 5th November, 2018
OCLC Number/Unique Identifier: 7929242579
Potassium is an important ion capable to maintain intra-extracellular electric gradient. Variations in the intra-extracellular ionic flow may alter cells functions, skeletal and smooth muscle contractility and electric activity of myocardial cells.
In this study we demonstrated that high level of serum potassium may be associated with cardiac and neurological life-threatening diseases.
We describe two case reports in which one patient, chronic hemodialysed, presented with cardiogenic shock in setting of hyperkalemia; the other, with end-stage kidney disease, showed a flaccid paralysis associated to high level of serum potassium during potassium sparing diuretic therapy.
Emergency haemodialysis was performed with a complete remission of the clinical manifestations.
Indeed, the use of simply diagnostic instruments such as serum electrolyte assay and electrocardiographic study (ECG) are helpful in clinical practice solving in timely serious complications due to hyperkalemia.
Scintigraphic non-invasive diagnosis of amyloid cardiomyopathy
Published on: 4th October, 2019
OCLC Number/Unique Identifier: 8457482817
Amyloidosis encompasses a heterogeneous group of disorders, characterized by extracellular deposition of insoluble abnormal amyloid aggregates, due to a failure in protein quality control. Cardiac amyloidosis is a disorder in which proteins misfold and deposit as amyloid fibrils that infiltrate the myocardial extracellular space [1].
Transthyretin (ATTR) and light chain (AL) are the most frequent types of cardiac amyloidosis. Transthyretin is a protein mainly synthesized by the liver, it may be hereditary or acquired from either wild-type (ATTRwt) or mutant (ATTRm) amyloid [2]. Cardiomyopathy is a common manifestation of ATTR amyloidosis with a particularly poor life expectancy of 2 to 6 years after diagnosis [3]. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific, and diagnosis largely relies on amyloid detection in tissue biopsies.
Glycosaminoglycans as Novel Targets for in vivo Contrast-Enhanced Magnetic Resonance Imaging of Atherosclerosis
Published on: 20th April, 2020
OCLC Number/Unique Identifier: 8588716816
Atherosclerosis is an important promoter of cardiovascular disease potentiating myocardial infarction or stroke. Current demand in biomedical imaging necessitates noninvasive characterization of arterial changes responsible for transition of stable plaque into rupture-prone vulnerable plaque. in vivo contrast enhanced magnetic resonance (MR) imaging (MRI) allows quantitative and functional monitoring of pathomorphological changes through signal differences induced by the contrast agent uptake in the diseased vessel wall, therefore it is the ideal modality toward this goal. However, studies have so far focused on the cellular targets of persisting inflammation, leaving extracellular matrix (ECM) far behind. In this review, we portray ECM remodeling during atherosclerotic plaque progression by summarizing the state of the-art in MRI and current imaging targets. Finally, we aim to discuss glycosaminoglycans (GAGs) and their functional interactions, which might offer potential toward development of novel imaging probes for in vivo contrast-enhanced MRI of atherosclerosis.
Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks
Published on: 2nd October, 2020
OCLC Number/Unique Identifier: 8689024240
With the discovery by Calghatgi (2013) that three common antibiotics (Abs) increased mitochondrial reactive oxygen (ROS) and lipid peroxide (LP) and depleted their natural absorbant glutathione led me to investigate further the potential impacts of these genotoxic substances on carcinogenesis. The range of impacts on mitochondria and cellular DNA varied by antibiotic to those consistent with known prior contributions to carcinogenesis. Specific cancers probably increased by these changes were HCC, RCC (KCC), CRC, cancer of the esophagus. Tumor suppressor gene mutations resulting from LP were noteworthy in this regard and mutations induced in CRC were consistent with those found in carcinogenesis of CRC. In addition depression of short chain fatty acids in microbiomes were found which depress the immune system increasing risk of all cancers. Many cancers were increased according to epidemiological studies linking Abs with elevated odds ratios, with one concern in particular, fatal breast cancer. The impact of loss of functionality of the mitochondria was also linked to depression of the citric acid cycle and therefore ATP which deflected metabolism to glycolysis, the Warburg mechanism also increasing risk of all cancers, favoured by cancer cells. In conclusion, some portion of many cancer types are probably increased in likelihood by number, type and frequency of Abs treatment and chronic residue exposure which varies from individual to individual. This led me to propose a three pronged carcinogenesis mechanism for Abs. 1. Cancer critical mutations 2. Immune depression 3. loss of mitochondrial functionality leading to Warburg effects. Damage to mitochondria were also noted by common pesticides tested in China and cancer associations were also found for many pesticides supporting a similar contributory etiology. Heart health concerns were raised by these findings because of the myriad mitochondria in the heart and because of long term reliability needs. Studies suggesting hearts were affected by Abs and pesticide exposure were presented. Because of their geographical ubiquitousness and the huge range of diseases associated with mitochondrial dysfunction, antibiotics and pesticides and bacteriocidal biocides are of concern for biodiversity and life in general. I propose research steps to evaluate Abs safety and suggest directions for further research and make suggestions on ways to ameliorate Abs toxicity.
Post-extrasystolic potentiation differentiates “true” from “pseudo” Low-flow, Low-gradient aortic stenosis
Published on: 16th December, 2020
OCLC Number/Unique Identifier: 8872657684
Post-extrasystolic potentiation (PESP) is a marker of contractile reserve and refers to the augmentation of left ventricular contractility due to preload recruitment and rise in intracellular calcium following a premature beat. In this case report we show that PESP might be a safe and helpful aid to evaluate low flow, low gradient aortic stenosis and contractile reserve in the cathlab, thereby reducing the potential risk of complications associated with intravenous dobutamine evaluation and reducing unnecessary testing.
Small cell carcinoma of the ovary with hypercalcemia: Case report and review of the literature
Published on: 3rd July, 2018
OCLC Number/Unique Identifier: 7815113047
We describe here the case of a 23-year old woman with small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT) with SMARC-A4 mutation who benefited from surgery in two steps leading to a total hysterectomy with bilateral salpingo-oophorectomy, omentectomy, pelvic and lombo-aortic lymph nodes dissection. She also received 6 courses of poly-chemotherapy after the surgery. A close follow-up was then performed by clinical examination every three months with determination of serum calcium and CA125 level as well as imaging with thoraco-abdominal CT scan. To date, the patient has a disease-free survival of more than 9 years. We also reviewed the literature on this topic and discuted the new diagnostic and prognostic genetic tool SMARC-A4 mutation.
Mechanism-related Teratogenic, Hormone Modulant and other Toxicological effects of Veterinary and agricultural surfactants
Published on: 18th September, 2017
OCLC Number/Unique Identifier: 7325078577
Veterinary and agricultural surfactants are supposed to be inert additives, yet these substances commonly exert biological side-effects, in given cases synergistic with those of the active ingredients of these preparations. This is explicitly seen in altered toxicity of veterinary or pesticide formulations compared to their active ingredients alone. Neither the individual effects of these excipients, nor such combination effects are well-studied in toxicology, and therefore, possible toxicity consequences are occasionally not being considered at sufficient significance in the authorization, use and control of these substances. Risk assessment of these substances should cover all hazards they may represent, and corresponding levels of exposure. Surfactants used in veterinary and pesticide formulation enter the environment either by direct dispersion or by indirect release through excrement, leaching, sewage waters or sludge, and in turn, create potential exposure to a number of non-target organisms. Biochemical and (eco)toxicological hazards recently identified regarding certain agricultural surfactants include cytotoxicity (on cell lines of epithelial, neural and other tissues, as well as stem cells and tumor cells), endocrine disrupting effects, as well as aquatic ecotoxicity. This Mini Review summarizes toxicological effects identified in our studies in aquatic toxicity tests, in cell viability and cytotoxicity tests, in estrogenic activity assays, correlated with biochemical analysis of the surfactants and their decomposition. The conclusions are hoped to facilitate environmentally precautious revision of surfactants widely used in agriculture.
Giant cellular angiofibroma of the vulva: case report
Published on: 9th May, 2019
Cellular Angiofibroma is a rare benign mesenchymal tumor without gender preference. It is usually a small (<3cm), well-circumscribed, mostly asymptomatic and typically slow growing. Surgical removal of the mass with its capsule is the preferred treatment, not only helps guarantee complete excision and prevent its recurrence but also minimize blood loss. We present the case of a 76-year-old woman with a giant vulvar mass.
Near Complete Response to 177Lu-PSMA-DKFZ-617 Therapy in a Patient with Metastatic Castration Resistant Prostate Cancer
Published on: 5th November, 2017
OCLC Number/Unique Identifier: 7286424598
Prostate specific membrane antigen, a type II transmembrane protein is an excellent target for the radionuclide therapy in advanced prostate cancer patients due to its high expression in the prostate cancer cells. We present the case of a 69-year old man with advanced metastatic castration resistant prostate cancer. In view of rising serum PSA levels despite hormonal and chemotherapy, we decided to perform a 68Ga-PSMA-HBED-CC PET/CT scan (prostate specific membrane antigen). It revealed intense radiotracer uptake in the prostate, lymph nodes and multiple skeletal sites. Five cycles of 177Lu-PSMA-DKFZ-617 radioligand therapy were administered in the patient followed by an intrim 68Ga-PSMA-HBED-CC PET/CT. Intrim 68Ga-PSMA-HBED-CC PET/CT scan demonstrated a near complete remission of disease with a corresponding decrease in the sPSA levels. During the follow-up duration of 12 months, the patient did not develop haematological, kidney and liver toxicity during the course of treatment and follow-up. 177Lu-PSMA-DKFZ-617 is a promising therapeutic option in metastatic castration resistant prostate cancer (mCRPC) patients.
Autoimmune encephalitis associated with an ovarian teratoma in a 29-year old woman
Published on: 15th May, 2019
OCLC Number/Unique Identifier: 8165450551
NMDA receptor encephalitis is a rare disease first described in 2007. Anti-NMDA receptor encephalitis affects mostly young women as neoplasms, mostly ovarian teratomas, are the underlying cause. The disease is caused by antibodies binding to extracellular epitopes of neuronal cell-surface, which leads to an internalization of NMDA-receptors. The characteristic syndrome of patients with anti-NMDAR as well as its recovery follows a certain pattern. Treatment includes immunotherapy and removal of the immunologic trigger. This case report describes a young woman with anti-NMDA receptor encephalitis caused by an ovarian teratoma.
Hyperthermia and Breast cancer: A short review
Published on: 17th October, 2017
OCLC Number/Unique Identifier: 7286427114
The main goal of hyperthermia is to elevate the tumor temperature to kill tumor cells and improve local control. The usage of hyperthermia is combination with radiotherapy or chemotherapy. Hyperthermia is delivered in different types of cancers like breast cancer, melanoma and sarcoma. Breast cancer treatment enroll surgery, chemotherapy, radiotherapy and hormone therapy. Hyperthermia is given once or twice a week concomitantly with radiotherapy or chemotherapy. This short review will enlight the types, physics, and the results of hyperthermia especially in the management of breast cancer therapy.
Role of Carcinoma Associated Fibroblasts in Anoikis Resistance in Oral Squamous Cell Carcinoma –need of the hour
Published on: 30th January, 2017
OCLC Number/Unique Identifier: 7317601183
Anoikis resistance (AR) is a favorable attribute exhibited by cancer cells for metastasis. Carcinoma associated Fibroblasts (CAFs) plays a crucial role in AR in various cancers. It was proved in array of studies in different cancers that there was definite interrelationship between CAFs and AR. But its role in OSCC is ambiguous. It is the need of the time to reveal the correlation of CAF and oral squamous cell carcinoma (OSCC) in relation with anoikis. Molecular pathways which affects the AR via CAFs in various cancers has been highlighted in this communication. Divulging the importance of CAF in cancer will aid in designing customized novel chemoprevention therapy and thus will help in enhancing the prognosis of patient in OSCC.
A great mimicker of Bone Secondaries: Brown Tumors, presenting with a Degenerative Lumber Disc like pain
Published on: 17th July, 2017
OCLC Number/Unique Identifier: 7317646408
This report presents an adult patient suffering from sacroiliitis like low back pain, lumbosacral radiculopathy and elbow swelling. Multimodality imaging revealed multiple lytic bone lesions located in supra acetabular iliac bone, sacrum, and distal end of radius. Painful numerous lesions due to the extension to the articular surfaces are not expected for Brown tumors. Less than ten cases with multiple Brown tumor due to primary hyperparathyroidism has been reported. Although Brown tumors are mostly diagnosed incidentally, this case would awake the physicians about rheumatological symptoms in the presentation of Brown tumors. Since Brown tumors are non-touch bone lesions that are expected to regress after parathyroid adenoma removal, it is important to distinguish Brown tumors from the giant cell tumors.
Gynaecological malignancies after breast cancer diagnosis: A population-based study
Published on: 31st October, 2019
OCLC Number/Unique Identifier: 8319364554
Background: Breast cancer (BC) is one of the most prevalent malignancies. BC survivors have higher risk of second primary cancers than the general population. There is an increased interest in BC survivor management, including the prevention of these second cancers. The aim of this study was to assess the risk of gynaecological malignancy (GM) as second neoplasm among BC patients in our population.
Methods: Patients with invasive BC diagnosed from 1980 to 2014 included in the Girona Cancer Registry were included. The incidence of second GM in these patients was compared to those in the general population. Second primary cancer was stated as a tumour diagnosed after 2 months from the BC diagnosis. Standardized incidence ratios (SIR) and absolute excess of risk (AER) were calculated.
Results: 9,717 patients were diagnosed with invasive BC during this period, with a median age at diagnosis of 61 years, and a median follow-up of 7.9 years. 117 of them developed a second GM. By tumour type, the only statistically significant higher SIR was observed for corpus uteri cancer (SIR:2.28 95% CI 1.82-2.83; AER:6.43 95% CI 4.13-9.14). After reviewing the histology of the corpus uteri cancer cases, we found that 71.4% were type I (endometrioid adenocarcinoma), 15.5% type II (serous adenocarcinomas and clear cell carcinomas), 10.7% carcinosarcomas, 2.4% sarcomas and there were no unspecified malignant neoplasms.
Conclusion: BC survivors have an increased risk of corpus uteri cancer, with an increase in unfavourable histologies compared to the general population. Lifelong primary and secondary prevention interventions should be recommended for these patients.
Imaging modalities delivery of RNAi therapeutics in cancer therapy and clinical applications
Published on: 4th March, 2021
OCLC Number/Unique Identifier: 9039869756
The RNA interference (RNAi) technique is a new modality for cancer therapy, and several candidates are being tested clinically. Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of ‘personalized medicine’.
Technologies on theranostic nanomedicines has been discussed. We designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90 nm, bright green fluorescence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. This chapter presents an over view of the current status of translating the RNAi cancer therapeutics in the clinic, a brief description of the biological barriers in drug delivery, and the roles of imaging in aspects of administration route, systemic circulation, and cellular barriers for the clinical translation of RNAi cancer therapeutics, and with partial content for discussing the safety concerns. Finally, we focus on imaging-guided delivery of RNAi therapeutics in preclinical development, including the basic principles of different imaging modalities, and their advantages and limitations for biological imaging. With growing number of RNAi therapeutics entering the clinic, various imaging methods will play an important role in facilitating the translation of RNAi cancer therapeutics from bench to bedside.
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