Cardiovascular and hormonal changes following haemorrhage in the anaesthetized Brattleboro rat with an extracorporeal circulation

An extracorporeal circulation technique was developed for use in rats to provide equilibrated blood samples for multiple hormone assays. The inclusion of the extracorporeal circulation did not significantly alter arterial blood pressure, cardiac output, heart rate or central venous pressure in either Brattleboro rats with hereditary diabetes insipidus (BDI) or normal rats of the parent Long Evans (LE) strain. Plasma adrenaline and noradrenaline levels did not alter in either BDI or LE rats following inclusion of the extracorporeal circulation but the vasopressin concentration rose significantly in the LE rats. The impaired recovery of the mean arterial blood pressure following haemorrhage in the BDI rats compared with normal LE animals was not further influenced by the inclusion of the extracorporeal circulation. Plasma vasopressin and adrenaline (but not nor-adrenaline) levels were significantly raised during, and after, haemorrhage in the LE rats while in the BDI rats only plasma adrenaline levels were significantly increased. These results show that the insertion of an extracorporeal circulation into an anaesthetized BDI or LE rat does not adversely affect the cardiovascular system despite the increase in baseline plasma vasopressin concentration in normal rats, and its subsequent removal provides an additional equilibrated blood sample for multiple hormone assay within the same animal. The increased release of both adrenaline and vasopressin (but not noradrenaline) after haemorrhage in the same animal is detected using this technique, and the importance of vasopressin to the normal recovery process confirmed.     

Therapeutic effect of adipose-derived mesenchymal stem cells on Cisplatin induced testicular damage in adult male albino rat

Infertility represents a major medical, economic, and psychological problem. Stem cells therapy for infertility has a great interest nowadays especially for cancer survivors at pre-reproductive and reproductive age.

 Thirty-two adult male albino rats were used, divided equally into four groups; Group I (Control group) received isotonic saline intraperitoneally (i.p.) as vehicle. Group II (Cisplatin-treated group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, and then were sacrificed after 5 days. Group III (Stem-cell-treated group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, then after 5 days received adipose-derived mesenchymal stem cells (ADMSCs) (1 × 10⁶). Cells were injected in the rete testis, then after 60 days, the animals were sacrificed. Group IV (Auto healing group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, and then left for 65 days then the animals were sacrificed. Cisplatin administration resulted in degenerative changes in the testicular architecture in the form of thickened irregular BM of seminiferous tubules. The germinal epithelium showed disorganization and marked reduction in the thickness, associated with Sertoli cells preservation. Features of apoptosis assured by elevated caspase-3 expression were noticed. The interstitium showed cellular infiltration and distorted Leydig cells. Injection of (ADMSCs) resulted in great improvement of testicular architecture and increase in the testosterone level associated with strong immune reaction of the CD-44. ADMSCs are recommended as a new treatment modality for male infertility.

Abbreviation: i.p.: intraperitoneally; BM: basement membrane; ADMSCs: adipose-derived mesenchymal stem cells; WHO: World Health Organization; MSCs: mesenchymal stem cells; DMEM: Dulbecco modified eagles media; PBS: phosphate-buffered saline; FACS: fluorescence-activated cell sorting; ELISA: enzyme-linked immunosorbent assay; CP: Cisplatin; ROS: reactive oxygen species; CAT: catalase; SOD: superoxide dismutase; OS: oxidative stress; SSCs: spermatogonia stem cells; GCs: germ cells; UCMSCs: umblical cord mesenchymal stem cells; TGFb1: transforming growth factor beta-1; BMP4: Bone morphogenic protein 4; BMP8b: bone morphogenic protein 8b.     

The prevalence of metabolic syndrome is increased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Purpose

Cardiovascular disease is one of the major causes of mortality in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Metabolic syndrome (MetS) is associated with increased cardiovascular risk in the normal population. However, MetS in AAV has not been adequately investigated. We aimed to determine MetS prevalence and associated factors in AAV patients.

Methods

Thirty-seven AAV patients and 42 healthy controls were enrolled. MetS was determined by International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. The relationship between clinical features of AAV and MetS was also investigated.

Results

MetS was significantly higher in AAV patients than controls by NCEP-ATPIII (51.4% vs. 26.2%, p 0.022) and IDF (62.2% vs. 35.7%, p 0.020). When AAV patients with MetS were compared to those without, there were significant differences in age, CRP, GFR and NT-pro-BNP. Age [58 (13) vs. 50 (8) years p: 0.028], CRP [4.0 (3.6) vs. 3.2 (1.0) mg/l, p 0.021] and NT-pro-BNP [173.5 (343.7) vs. 106.0 (103.0) pg/ml, p 0.013] were significantly higher in AAV patients with MetS than those without; GFR was significantly lower [38 (46) vs. 83 (51) ml/min/1.73 m², p 0.004]. ROC curve analysis showed NT-pro-BNP?>?58.0 ng/ml predicted MetS with 87.1% sensitivity and 46.7% specificity (Area under curve: 0.71, CI 0.536–0.902, p 0.041). Multivariate analysis revealed age [OR (95% CI): 1.180 (1.010–1.370), p 0.039] and NT-pro-BNP?>?58 pg/ml [OR (95% CI): 5.5 (1.02–30.1) p 0.047] were independent predictors of MetS in AAV patients.

Conclusion

MetS is significantly higher in AAV patients than controls and is associated with age and NT-pro-BNP. Screening and treating MetS may improve prognosis in AAV patients.

     

Takayasu’s arteritis occurring under TNF blockers in a patient with spondyloarthritis: is it an association or a paradoxical effect?

Coexistence of spondyloarthritis (SpA) and Takayasu’s arteritis is not a common finding, but such cases have been discussed, particularly in the context of choice of therapy. Inhibition of inflammation by tumor necrosis factor inhibitors (TNFi) is a key aspect of the treatment of SpA and also positive effects of such treatment in concomitant large vessel vasculitis have been reported. However, TNFi is also associated with the possibility of initiating vasculitis.The present article based on a case study and the available literature is an attempt to discuss coexistence of these two diseases and the impact of treatment with biological drugs from the anti-TNF group in the course of SpA with Takayasu’s arteritis.     

Synthesis of some heterocycles of potential biological activity

A convenient method for the preparation of imidazobenzimidazole3, imidazoimidazole5, imidazotriazole6 and pyrano [2, 3-c] oxazole7 derivatives is described. This depends on interaction of 2-methyl-4-arylidene-2-oxazolin-5-ones1 with o-diamines, thiosemicarbazide and/or ethylcyanoacetate. The effect of alcoholic potassium cyanide on oxazolinone1 was studied. Antibacterial activity of the obtained products was studied.     

A Associação de TWEAK com Calcificação da Artéria Coronária em Pacientes com Doença Renal Crônica

BackgroundThe soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) is a member of the TNF superfamily that plays a critical role in proliferation and inflammation in the arterial circulation.ObjectivesThis prospective study aimed to show the relationship between the sTWEAK levels and coronary artery calcification (CAC) in patients with chronic kidney disease (CKD).MethodsThis prospective study included 139 consecutive patients undergoing computed coronary angiography for any reason except for acute coronary syndromes from August 2020 to February 2021. A total of 12 patients were excluded from the study due to exclusion criteria. Patients were divided into two groups with regard to having a CAC score of less than 400 (n=84) and 400 or more (n=43). Significance was assumed at a 2-sided p<0.05.ResultsAs the CAC score increased, sTWEAK levels presented a statistically significant decrease, and a strong relationship between sTWEAK levels and the CAC score (r: -0.779, p<0.001) was observed. The ROC analysis revealed that the optimal cut-off level of sTWEAK for predicting the CAC score of 400 was 761 pg/mL with a sensitivity of 71% and a specificity of 73% (AUC: 0.78; 95% CI:0.70-0.85; p < 0.001)ConclusionsEven though the large-scale studies showed a positive correlation between eGFR and the sTWEAK levels, some studies found the increased sTWEAK levels to be associated with mortality and the severity of the coronary artery system in patients with CKD. Our results support our hypothesis that the sTWEAK level shows coronary calcification rather than other types of atherosclerotic plaques.     

Investigation of Eating Habits in Patients with Functional Dyspepsia

Background:Nutritional habits of patients with functional dyspepsia can affect the progression of functional dyspepsia. We aimed to determine the foods and dietary habits that may cause symptoms of postprandial fullness, early satiety, epigastric pain, and epigastric burning in functional dyspepsia patients.Methods:Sixty functional dyspepsia patients, who were diagnosed according to Rome IV criteria in the endoscopy unit of a gastroenterology institute, were included in the study. Data on the demographic characteristics, anthropometric measurements, nutritional habits, and food consumption frequency questionnaire of functional dyspepsia patients were collected.Results:Postprandial fullness was found more common in those who preferred roasting as a cooking method. There was no significant difference between symptoms and meal frequency. Epigastric burning and pain were found to be more pronounced in women, and alcohol consumption was less in patients who experienced more epigastric pain. In non-smoker participants, the complaint of early satiety was lower. It was found that broccoli, radish, celery, green olives, and olive oil consumption was less in participants who experienced excessive postprandial fullness. Patients with stomach pain consumed less dry fruits, green olives, butter, alcohol, and fast food. It was found that patients with stomach burning consumed less alcohol and fast food.Conclusion:In conclusion, functional dyspepsia patients should avoid or reduce consuming broccoli, radish, celery, green olives, olive oil, dry fruits, and butter which may trigger symptoms. Reducing consumption of these foods, abandoning unhealthy cooking methods such as roasting, reducing smoking, and reducing consumption of alcohol and fast food might be beneficial for relieving symptoms.     

The value of adjacent vessel sign in malignant breast tumors

PURPOSE The aim of this study was to evaluate the prognostic quality of adjacent vessel sign (AVS) in malignant breast tumors by comparing it with classical prognostic pathological biomarkers and magnetic resonance imaging (MRI) findings.METHODS A total of 124 patients with 133 malignant lesions were included. All the imaging was performed on a 1.5T Avanto scanner and the images were interpreted according to BI-RADS-MR® (fifth ed.) atlas. Maximum intensity projection (MIP) images were constructed from subtracted post-contrast images and were used to investigate AVS. Histopathological results and MRI findings were compared with AVS.RESULTS Interobserver agreement about AVS status was substantial (κ = 0.64). AVS positive lesions were significantly bigger in size (P < .001, AVS negative: median 12 mm, AVS positive: median 31 mm). AVS was significantly associated with increased Ki-67 index and axillary lymph node metastasis (P = .009 and P = .019, respectively). Between AVS and lymphovascular invasion (LVI), there was a trend toward positive relationship (P = .076). MRI findings of T2 hypointensity, peritumoral edema, irregular shape, non-homogeneous contrast enhancement, rapid early contrast enhancement, and skin infiltration showed significant positive relation with AVS (P < .001, P < .001, P < .001, P = .02, P = .021, and P = .021, respectively). AVS is found to be associated with increased Ki-67 index, axillary lymph node metastasis, and some MRI findings that point to malignancy or poor prognosis.CONCLUSION AVS indicates poor prognosis since it is related to axillary lymph node metastasis, increased Ki-67 index, LVI, peritumoral edema, rapid early contrast enhancement, increased background enhancement, skin extension, T2 hypointensity, non-homogeneous contrast enhancement, irregular lesion shape, and larger tumor size. AVS is an easy to use sign that shows substantial interobserver agreement.

Main points

• Adjacent vessel sign (AVS) shows poor prognosis since it is related to axillary lymph node metastasis, increased Ki-67 index, lymphovascular invasion, peritumoral edema, rapid early contrast enhancement, increased background enhancement, and skin extension.
• AVS is also associated with T2 hypointensity, non-homogeneous contrast enhancement, irregular lesion shape, and larger tumor size which all point out malignant lesion character.
• AVS is an easily and rapidly applicable sign showing substantial interobserver agreement.

Breast cancer is the number one cause of cancer-related deaths in women.¹ Tumor cells need neovascularization to stay alive, grow, invade, or spread. Studies show that contrast enhancement pattern in magnetic resonance imaging (MRI) is related to microvessel density, neovascularization, and prognostic parameters.^2-5 Also, tumor-bearing breast shows increased vascularity compared to the contralateral breast, and this is found to be related to prognostic indicators.^6-8 Asymmetrical increased vessels, first mentioned by Sievert in 1997, were later described by Sardanelli in 2005 as increased number of vessels 2 mm or thicker and 3 cm or longer, compared with the contralateral breast.^6,7,9,10 As one can easily appreciate, this method is laborious, time-consuming, and impractical. On the other hand, an adjacent vessel sign (AVS) is more easily and rapidly applicable. AVS was first defined by Carriero et al.¹¹ as a vessel (either artery or vein) in contact with a lesion or entering it. Besides, AVS can be used in bilateral breast cancer or patients with mastectomy whereas asymmetrical increased vessels can be used only when a normal contralateral breast exists (Figure 1). Maximum intensity projection (MIP) series constructed from early postcontrast images are best to search for AVS since breast parenchyma is less enhanced (Figure 2). AVS is associated with malignancy.^4,12,13 Only a few studies about the prognostic value of AVS are found in the literature.^4,14Open in a separate windowFigure 1.60-year-old woman with invasive carcinoma of no special type (IC-NST) on the right breast (thick white arrow) and invasive papillary carcinoma on the left breast (thick black arrow), both positive for adjacent vessel sign (AVS) on maximum intensity projection (MIP) imaging (thin arrows). Asymmetrical increased vascularity cannot be used in this case since both breasts bear malignancy. Instead, AVS can be readily utilized.Open in a separate windowFigure 2.a-d. Early through late MIP images (a-d); AVS appears best at early series (a, arrow).Prognostic factors in breast cancer provide information about the course of the disease before surgery and are irrelevant to neoadjuvant therapy. Patient age, axillary lymph node metastasis, tumor size, type, histopathologic grade, lymphovascular invasion (LVI), tumor proliferation speed (Ki-67), oncogenes (Her-2/neu), tumor suppressor genes (p53), and estrogen and progesterone receptor (ER and PR) are independent classic prognostic factors.¹⁵ Predictive factors show possible response to treatment but cannot demonstrate the disease course. ER, PR, Ki-67, and HER2 existence or percent are both prognostic and predictive parameters.In this study, we aimed to assess the relationship between AVS and classical pathological prognostic-predictive parameters and MRI findings in malignant breast tumors.     

Design,Structural Inspection and Bio-Medicinal Applications of Some Novel Imine Metal Complexes Based on Acetylferrocene

Some novel imine metal chelates with Cr³⁺, Mn²⁺, Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, and Cd²⁺ cations were produced from 2-acetylferrocene and 3-aminophenol. The new acetylferrocene azomethine ligand ((Z)-cyclopenta-1,3-dien-1-yl(2-(1-((3-hydroxyphenyl)imino)ethyl)cyclopenta-2,4-dien-1-yl)iron) and its metal ion chelates were constructed and elucidated using FT-IR, UV/Vis, ¹HNMR, DTA/TGA, CHNClM studies, mass spectrometry and SEM analysis. According to the TGA/DTG investigation, the ferrocene moiety spontaneously disintegrates to liberate FeO. The morphology of the free acetylferrocene azomethine via SEM analysis was net-shaped with a size of 64.73 nm, which differed in Cd(II) complex to be a spongy shape with a size of 42.43 nm. The quantum chemical features of the azomethine ligand (HL) were computed, and its electronic and molecular structure was refined theoretically. The investigated acetylferrocene imine ligand behaves as bidinetate ligand towards the cations under study to form octahedral geometries in case of all complexes except in case of Zn²⁺ is tetrahedral. Various microorganisms were used to investigate the anti-pathogenic effects of the free acetylferrocene azomethine ligand and its metal chelates. Moreover, the prepared ligand and its metal complexes were tested for anticancer activity utilizing four different concentrations against the human breast cancer cell line (MCF7) and the normal melanocyte cell line (HBF4). Furthermore, the binding of 3-aminophenol, 2-acetylferrocene, HL, Mn²⁺, Cu²⁺, and Cd²⁺ metal chelates to the receptor of breast cancer mutant oxidoreductase was discovered using molecular docking (PDB ID: 3HB5).