Leishmania Donovani. Hamster macrophage interactions in vitro: cell entry, intracellular survival, and multiplication of amastigotes

An in vitro system was developed for studying host-parasite cellular interactions in visceral leishmaniasis with amastigotes isolated from infected spleens of hamsters and their peritoneal macrophages maintained by an improved method. The culture system supports the growth of Leishmania donovani amastigotes with different parasite/macrophage ratios for up to 2 wk, yielding results more consistent and reproducible than previously possible. Results indicated that the “forms” of the amastigotes (with or without adherent host membranes) and the “state” of the macrophages (with or without stimulation in vivo by thioglycollate or in vitro by aging) had no effect on the growth rate of the parasites, which, however, seems to vary with the macrophage subpopulations. An electron microscope study suggests that amastigotes are ingested through phagocytosis by the macrophages and become lodged in loose phagosomes. Additional evidence with quantitative data is presented to support the earlier findings that phagosome-lysosome fusion occurs after the interiorization of the parasites and that they not only survive but multiply in these vacuoles. During the postinfection periods, reorientation of amastigotes in vacuolar space results in the appearance of three types of parasitophorous vacuoles (parasites in loose vacuoles, in tight-fitting vacuoles or abutting in part against the inner lining of vacuoles). The last category may be the predominant type giving rise to the variations observed. Exogenously introduced dense marker accumulated in these parasitophorous vacuoles of the macrophages infected for several days indicating a continuous accessibility of amastigotes to the ambient mestruum via phagosome-lysosome vacuolar system of the host cells. This finding may have significant implications in parasite nutrition, host immunity, and chemotherapy of leishmaniasis.     

Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide

Objectives

Mechanisms underlying contrast medium (CM)-induced nephropathy remain elusive, but recent attention has been directed to oxygen availability. The purpose of this study was to evaluate the effect of the low-osmolar CM iopromide and the iso-osmolar CM iodixanol on oxygen consumption (QO₂) in freshly isolated proximal tubular cells (PTC) from kidneys ablated from elderly humans undergoing nephrectomy for renal carcinomas and from normoglycemic or streptozotocin-diabetic rats.

Materials

PTC were isolated from human kidneys, or kidneys of normoglycemic or streptozotocin-diabetic rats. QO₂ was measured with Clark-type microelectrodes in a gas-tight chamber with and without each CM (10 mg I/mL medium). L-NAME was used to inhibit nitric oxide (NO) production caused by nitric oxide synthase.

Results

Both CM reduced QO₂ in human PTC (about –35%) which was prevented by L-NAME. PTC from normoglycemic rats were unaffected by iopromide, whereas iodixanol decreased QO₂ (–34%). Both CM decreased QO₂ in PTC from diabetic rats (–38% and –36%, respectively). L-NAME only prevented the effect of iopromide in the diabetic rat PTC.

Conclusions

These observations demonstrate that CM can induce NO release from isolated PTC in vitro, which affects QO₂. Our results suggest that the induction of NO release and subsequent effect on the cellular oxygen metabolism are dependent on several factors, including CM type and pre-existing risk factors for the development of CM-induced nephropathy.     

Disparities in prostate cancer incidence and mortality rates: Solvable or not?

Prostate cancer (PCa) is recognized as a disease possessing not only great variation in its geographic and racial distribution but also tremendous variation in its potential to cause morbidity and death and it, therefore, ought not to be considered a homogenous disease entity. Morbidity and death from PCa are disproportionately higher in men of African ancestry (MAA) who are generally observed to have more aggressive disease and worse outcomes following treatment compared to men of European ancestry (MEA). The higher rates of PCa among MAA relative to MEA appear to be multifactorial and related to inherent differences in biological aggressiveness; a continued lack of awareness of the disease and methods of prevention; a lower prevalence of screen-detected PCa; comparatively lower access to quality healthcare as well as systemic and institutionalized disparities in the administration of optimal care to MAA in developed countries such as the United States of America where high-quality care is available. Even when access to quality healthcare is assured in equal access settings, it appears that MAA still have worse outcomes after PCa treatment stage-for-stage and grade-for-grade compared to MEA, suggesting that, inherent racial, ethnic and biological differences are paramount in predicting poor outcomes. This review has explored the different contributing factors to the current disparities in PCa incidence and mortality rates with emphasis on the incongruence in how research has been conducted in understanding the disease towards developing therapies.     

Delayed embolization of ductal occluder device into the aorta with near-complete obstruction of the aorta and critical cardiac decompensation

Delayed embolization of ductal occluder device into the aorta after transcatheter closure of a patent ductus arteriosus (PDA) with almost complete obstruction of the aorta is extremely rare. Our patient had delayed migration of a ductal occluder device into the descending thoracic aorta (DTA) 6 months after its deployment. Because of critical biventricular dysfunction, urgent surgical removal of the device from the descending aorta was done via left posterolateral thoracotomy without using cardiopulmonary bypass. PDA was not closed because of doubt about the reversibility of pulmonary artery hypertension and severe right ventricular dysfunction so that it can act as an outlet to the decompensated right ventricle. The patient made an uneventful recovery. The patient was started on pulmonary vasodilators and is planned for right heart catheterization study after 2 months to check for the operability of PDA.     

Dextrocardia,situs solitus,inlet ventricular septal defect (VSD), and iatrogenic tricuspid regurgitation (TR)―A surgical perspective

Dextrocardia with situs solitus is a rare congenital anomaly, often associated with intra- or extracardiac malformations. A clear understanding of the spatial orientation of the chambers of the heart for planning surgical approach, is imperative. Access to the right side of the heart, especially for repair of the tricuspid valve can be challenging. We describe a case of dextrocardia, situs solitus, inlet ventricular septal defect (VSD) with iatrogenic tricuspid regurgitation (TR) in an adult patient, highlighting the surgical aspects essential for a successful outcome.     

Pulmonary valve neocuspidisation with glutaraldehyde-treated autologous pericardium—A novel technique in pulmonary valve endocarditis

Infective endocarditis (IE) is a serious condition leading to heart failure, persistent sepsis. The management of IE involving valve is mainly excision of the infected valve and replacement with a heart valve; which are also at the risk of prosthetic valve endocarditis. Hence repair of the valve with autologous pericardium is much more physiological. We had a 20-year-old male presented with features of heart failure and high-grade fever not responding to optimum medical management. Two-dimensional echocardiogram revealed vegetation on pulmonary valve cusps with the erosion of the left and right cusps. Neo cusps with autologous pericardium offered good hemodynamics with trivial regurgitation. The patient is doing well with normal pulmonary valve function 3 months after surgery. This technique is reliable, economic, and easily reproducible.     

Unusual presentation and rupture of left sinus of Valsalva into mitral-aortic intervalvular fibrosa

Ruptured sinus of Valsalva aneurysm from the left coronary sinus communicating through the mitral-aortic intervalvular fibrosa is rare. We report a 35-year-old patient who presented with only hemoptysis without any other cardiac complaint. The patient with this unusual diagnosis and presentation was managed successfully.     

Anomalous origin of left vertebral artery from descending thoracic aorta: A rare variant

We present a case of a 4-year-old child operated previously for cyanotic congenital heart disease where the follow-up computed tomography (CT) angiography revealed anomalous origin of the left vertebral artery from the descending thoracic aorta. This case also highlights the potential implications of this variant and the value of CT angiography in diagnosing this anomaly.