β-Asarone Exhibits Antifungal Activity by Inhibiting Ergosterol Biosynthesis in Aspergillus niger ATCC 16888

Fungi play an important role in the degradation of leather goods. Economics often influence the choice of fungicide, thus, search for highly effective and low cost fungicides is immensely important. The authors have screened antifungal activity of ten Indian traditional medicinal plants viz Acalypha fruticosa, Acalypha indica, Aegle marmelos, Adathoda vasika, Calotropis gigantea, Erythrina indica, Morinda citrifolia, Nerium oleander, Pithecellobium dulce, and Acorus calamus based upon their traditional knowledge and usage. Various solvent extracts and essential oils were screened for antifungal activity against Aspergillus niger. The antifungal potency was compared to untreated control and standard antifungal drugs itraconazole and voriconazole. The bioactive principle from highly active fragment was isolated and chemically characterized. The mode of action was determined by a range of studies that include the lesion of plasma membrane, ergosterol content in the plasma membrane, acidification of external medium, and mitochondrial dehydrogenase activity in A. niger ATCC 16888. Among the ten plants studied, A. calamus exhibited greater antifungal potency in comparison to untreated control and standard drugs itraconazole and voriconazole. The minimum inhibitory concentration of both methanolic extract and essential oil of A. calamus against A. niger ATCC 16888 is around 5 µg/ml. The authors identified β-Asarone as the bioactive principle of A. calamus using spectral studies viz ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy and gas chromatography coupled mass spectroscopy. The results indicate that β-Asarone interfere and reduces the ergosterol content in the plasma membrane of A. niger ATCC 16888 thus exert their antifungal activity.

     

Surgeons often underestimate the amount of blood loss in replacement surgeries

Objective：To assess the accuracy of the clinically estimated blood loss （EBL） when compared with the actual blood loss （ABL） in replacement surgeries.Methods：This prospective study was done in Sri Ramachandra Medical Centre from April 2011 to April 2013.Altogether 140 patients undergoing total hip replacement or total knee replacement were included with the inclusion criteria being patients with haemoglobin higher than 100 g/ml and coagulation profile within normal limits.Exclusion criteria were intake of antiplatelet drug or anti-coagulant,bleeding disorders,thrombotic episode,and haematological disorders.There were 65 men and 75 women.In this study,the consultants were free to use any clinical method to estimate the blood loss,including counting the blood-soaked mops and gauze pieces （estimating the volume of blood carded in all the mops and gauzes）,measuring blood lost to suction bottles and blood in and around the operative field.The ABL was calculated based on a modification of the Gross＇s formula using haematocrit values.Results：In 42 of the 140 cases,the EBL exceeded the ABL.These cases had a negative difference in blood loss （or DIFF-BL＜0） and were included in the overestimation group,which accounted for 30％ of the study population.Of the remaining 98 cases （70％）,the ABL exceeded the EBL.Therefore they were put into the underestimation group who had a positive difference in blood loss （DIFF-BL＞0）.We found that when the average blood loss was small,the accuracy of estimation was high.But when the average blood loss exceeded 500 ml,the accuracy rate decreased significantly.This suggested that clinical estimation is inaccurate with the increase of blood loss.Conclusion：This study has shown that using clinical estimation alone to guide blood transfusion is inadequate.In this study,70％ of patients had their blood loss underestimated,proving that surgeons often underestimate blood loss in replacement surgeries.     

Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82Rb PET/CT in predicting lesion-related outcome

European Journal of Nuclear Medicine and Molecular Imaging - Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC),...     

Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia

We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed ∼15,000 leukocytes (CD45^+high cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to ∼5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8⁺ T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4⁺ T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were ∼50% fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion.     

Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease.     

Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis

We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.     

ACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy loss

AIM: To assess the association between polymorphisms in angiotensin converting enzyme and methylene tetrahydrofolate reductase genes and recurrent pregnancy loss by a case-control study in South Indian women. METHODS: DNA was extracted from peripheral blood leukocytes of 104 women with Recurrent Pregnancy Loss (RPL) and 120 controls. Genotyping of ACE Insertion Deletion and MTHFR C677T polymorphism were carried out by PCR and PCR-RFLP, respectively. RESULTS: No statistically significant difference was observed in the distribution of genotypes between cases and controls for ACE and MTHFR polymorphisms. Further, the combination of MTHFR and ACE genotypes failed to reveal an association. CONCLUSION: In conclusion, the present study reveals lack of association of MTHFR C677T and ACE I/D polymorphisms in RPL in South Indian women. However, we cannot exclude the possibility that other polymorphisms of ACE and MTHFR genes could be associated with the disease and might be clinically useful as a marker to assess risk for RPL.     

Acute Renal Failure after Cesarean Section

Urinary ascites is a rare diagnosis, commonly associated with bladder rupture. We present a case of intraperitoneal bladder injury following a Cesarean section with subsequent development of urinary ascites. Initial laboratory data with elevated serum creatinine and blood urea nitrogen (BUN) raised the suspicion for acute kidney injury due to the recent obstetrical procedure. This case highlights the importance of including intraperitoneal bladder injury with urinary ascites as a key differential in the workup of acute renal failure, particularly in the obstetric surgical setting. The rapid development of ascites with elevated serum BUN and creatinine should prompt work up for evaluating intraperitoneal bladder injury. Early diagnosis and treatment can yield gratifying results and avoid unnecessary workup of other causes of renal failure.