Participation of miR-200 in pulmonary fibrosis

Excessive extracellular matrix production by fibroblasts in response to tissue injury contributes to fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF). Epithelial-mesenchymal transition, involving transition of alveolar epithelial cells (AECs) to pulmonary fibroblasts, appears to be an important contributory process to lung fibrosis. Although aberrant expression of microRNAs (miRs) is involved in a variety of pathophysiologic processes, the role of miRs in fibrotic lung diseases is less well understood. In the present study, we found that miR-200a, miR-200b, and miR-200c are significantly down-regulated in the lungs of mice with experimental lung fibrosis. Levels of miR-200a and miR-200c were reduced in the lungs of patients with IPF. miR-200 had greater expression in AECs than in lung fibroblasts, and AECs from mice with experimental pulmonary fibrosis had diminished expression of miR-200. We found that the miR-200 family members inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition of AECs. miR-200 family members can reverse the fibrogenic activity of pulmonary fibroblasts from mice with experimental pulmonary fibrosis and from patients with IPF. Indeed, the introduction of miR-200c diminishes experimental pulmonary fibrosis in mice. Thus, the miR-200 family members participate importantly in fibrotic lung diseases and suggest that restoring miR-200 expression in the lungs may represent a novel therapeutic approach in treating pulmonary fibrotic diseases.     

Coinfection of Leptomonas seymouri and Leishmania donovani in Indian leishmaniasis

Leishmania donovani is considered the causative organism of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Testing of 4/29 DNA samples from VL and PKDL patients as well as 2/7 field isolates showed an aberrant internal transcribed spacer 1 (ITS1) restriction fragment length polymorphism (RFLP) pattern, which upon sequencing strongly matched Leptomonas seymouri, thus confirming its presence in Indian leishmaniasis.     

Colonization with vancomycin-intermediate Staphylococcus aureus strains containing the vanA resistance gene in a tertiary-care center in north India

A nasal carriage survey for methicillin-resistant Staphylococcus aureus (MRSA) in an intensive care unit detected four strains of MRSA with reduced susceptibility to vancomycin. The vanA gene was found in two of these vancomycin-intermediate Staphylococcus aureus (VISA) strains. The absence of selective vancomycin pressure might have resulted in reduced expression of the resistant gene.     

Pressure Overload Induces Early Morphological Changes in the Heart

Cardiac hypertrophy, whether pathological or physiological, induces a variety of additional morphological and physiological changes in the heart, including altered contractility and hemodynamics. Events exacerbating these changes are documented during later stages of hypertrophy (usually termed pathological hypertrophy). Few studies document the morphological and physiological changes during early physiological hypertrophy. We define acute cardiac remodeling events in response to transverse aortic constriction (TAC), including temporal changes in hypertrophy, collagen deposition, capillary density, and the cell populations responsible for these changes. Cardiac hypertrophy induced by TAC in mice was detected 2 days after surgery (as measured by heart weight, myocyte width, and wall thickness) and peaked by day 7. Picrosirius staining revealed increased collagen deposition 7 days after TAC; immunostaining and flow cytometry indicated a concurrent increase in fibroblasts. The findings correlated with angiogenesis in TAC hearts; a decrease in capillary density was observed at day 2, with recovery to sham-surgery levels by day 7. Increased pericyte levels, which were observed 2 days after TAC, may mediate this angiogenic transition. Gene expression suggests a coordinated response in growth, extracellular matrix, and angiogenic factors to mediate the observed morphological changes. Our data demonstrate that morphological changes in response to cardiovascular injury occur rapidly, and the present findings allow correlation of specific events that facilitate these changes.The process of cardiac remodeling is responsible for changes in cardiac morphology and function. Left ventricular hypertrophy, which is observed in response to a variety of pathophysiological signals, is a typical response to pressure overload or any disease state that increases cardiac wall stress and marks an adaptive response to compensate to the unfavorable conditions. Both mechanical and chemical stressors induce cardiac remodeling, and over time the adaptive response concedes to cardiac dilatation and the ensuing remodeling process becomes maladaptive, leading to dysfunction,¹ possibly as a result of enhanced catecholamine chemical signaling by monoamine oxidases.² Factors associated with cardiac remodeling include myocyte hypertrophy, increased extracellular matrix (ECM) deposition, and abnormalities of the coronary vasculature.^3,4 The latter two conditions often combine to create perivascular fibrosis, and previous studies have demonstrated that reducing myocardial fibrosis improves coronary hemodynamics.⁵ In addition, proliferation of nonmyocyte constituents (ie, fibroblasts, endothelial cells, immune cells, and smooth muscle cells) encourages disorganized tissue heterogeneity,⁴ which is initially adaptive but subsequent overcompensation induces pathological cardiac remodeling.⁶Two principal elements of pathological hypertrophic remodeling that lead to malfunction are accumulation of collagen and vascular remodeling.⁷ An increase in collagen deposition stiffens the heart, resulting in systolic and diastolic dysfunction,⁸ whereas insufficient angiogenesis deprives the hypertrophic myocardium of oxygenation because of low capillary density.^9–11 Numerous studies have attempted to alter these remodeling processes, with varying success. Some authors have identified a relationship between the degree of hypertrophy and prognosis: higher survival rates were observed in patients treated before left ventricular end systolic diameter reaches 40 mm,¹² thus illustrating the importance of early intervention. Others have succeeded in correlating markers of fibrosis with left ventricular hypertrophy and clinical heart failure,^13,14 indicating that the combination of hypertrophy and fibrosis results in cardiac dysfunction. In addition, it has been shown that treatment to increase capillary density after a pathological insult is accompanied by improved cardiac function, even if delayed treatment is unable to decrease myocardial infarct size,¹⁵ suggesting that capillary density may be more of a determining factor than is tissue remodeling.One overlooked aspect is the time course within which these changes take place after pathological insult and their progression in relation to each other. Mainly, studies have investigated only later time points (day 7 and later), when advanced stages of remodeling, adaption, and pathology have already manifested in the heart.¹⁶ Limited studies examining early responses to pathology have uncovered important, cell-specific acute responses,¹⁷ but additional research is needed for a better understanding of the immediate response by the heart to injury. In the present study, we analyzed the acute morphological response within the first week after pathological cardiac insult, to determine the early progression of cardiac remodeling and correlate these remodeling events to better understand the complex coordination and how it relates to cardiac function. Here, we illustrate immediate changes in cardiac hypertrophy, angiogenesis, fibrosis, and alterations in the cell populations contributing to these events. We also propose possible gene-specific changes that may guide these morphological changes.     

Management of calcaneal malunion

The potential for disabling malunion following calcaneal fracture is high, regardless whether a patient is treated nonsurgically or surgically. Fracture displacement typically results in loss of hindfoot height, varus heel position, and widening of the hindfoot, with possible subfibular impingement and irritation of the peroneal tendon and/or sural nerve. Frequently, the subtalar joint develops posttraumatic arthritis. In symptomatic patients with calcaneal malunion, systematic evaluation is required to determine the source of pain. Nonsurgical treatment, such as activity modification, bracing, orthoses, and injection, is effective in many patients. Surgical treatment may involve simple ostectomy, subtalar arthrodesis with or without distraction, or corrective calcaneal osteotomy. A high rate of successful arthrodesis and of patient satisfaction has been reported with surgical management.     

Human stem cell therapy in ischaemic stroke: a review

Stroke is a leading cause of death and disability. Globally, 15 million people suffer a stroke each year, of whom more than 5 million die, and a further 5 million are left permanently disabled. Current treatment options offer modest benefits, and there is a pressing need for new and effective treatments. Stem cell therapy is a well-established treatment modality for various haematological diseases, with its use now being explored in different disease processes, including various neurological diseases, as well as vascular conditions such as ischaemic heart disease and peripheral vascular disease. Promising results have been seen in animal models of stroke, with evidence of significant functional benefits. Translation to the bedside, however, is in its early stages. This review will discuss the scientific background to stem cell therapy in ischaemic stroke, including evidence from current clinical trials.     

Relation between the presence and extent of coronary lipid core plaques detected by near-infrared spectroscopy with postpercutaneous coronary intervention myocardial infarction

We aimed to examine whether an association exists between the presence and extent of coronary lipid core plaques (LCPs) detected by near-infrared spectroscopy (NIRS) performed before percutaneous coronary intervention (PCI) with postprocedural myocardial infarction (MI). NIRS was performed in the native coronary arteries of 30 patients before PCI. Angular extent of LCP, lesion segment lipid core burden index, and block chemogram were evaluated. Cardiac biomarkers were measured before and 16 to 24 hours after PCI to determine occurrence of postprocedural MI. Mean number of 2-mm yellow blocks within the stented lesion was 1.4 ± 2.1 and mean lesion lipid core burden index was 110.3 ± 99. Using a definition of creatine kinase-MB >1 time upper limit of normal (ULN), >2 times ULN, and >3 times ULN, MI after PCI occurred in 23%, 13%, and 10% of patients, respectively. Compared to patients who did not have MI after PCI, those who did had similar clinical characteristics but received more stents and had more blocks within the stented lesion. Creatine kinase-MB increase >3 times ULN was observed in 27% of patients with ≥1 yellow block versus in none of the patients without a yellow block within the stented lesion (p = 0.02). In conclusion, PCI of LCP-positive lesions as assessed by NIRS is associated with increased risk for MI after PCI. NIRS may allow lesion-specific risk stratification before PCI and optimization of PCI strategies for myocardial injury risk minimization.