An echocardiographic assessment of cardiovascular hemodynamics in patients with large pleural effusion

BackgroundThe close relationship between pleural space and pericardial space and the dependence of their pressure kinetics are well known. This study evaluates the effects of increased intra pleural pressure due to pleural effusion on cardiovascular system.MethodsForty patients above the age of 12 who had massive unilateral/bilateral pleural effusion due to non-cardiac etiology were included in the study. Therapeutic thoracocentesis was done for massive pleural effusion. The echocardiographic parameters measured before and after thoracocentesis were compared.ResultsMean age of the patients 46.6 years. Out of 40 patients 8 were females (20%). 7 patients had right atrial collapse on echo. 85% of patients had significant flow velocity changes across both tricuspid valve and mitral valve during phases of respiration.11 patients (47.82%) had IVC compressibility of <50% during inspiration. Mean flow velocity respiratory variations across tricuspid valve before thoracocentesis and after thoracocentesis E 45.04 ± 10.3,32 ± 11.3% (p value <0.001), A 53.71 ± 28%, 32.08 ± 12.5% (p < 0.001) across mitral valve E 32.30 ± 12%, 19.78 ± 7.8% (p < 0.001), A 26 ± 11.2%, 21 ± 9.3% (p 0.006) across pulmonary artery 42.63 ± 31.3%, 17.70 ± 6.2% (p < 0.001), across aorta 21.57 ± 11.4%, 14.08 ± 7.6% (p < 0.001).ConclusionLarge pleural effusion has a potential to cause adverse impact on the cardiovascular hemodynamics, which could manifest as tamponade physiology. Altered cardiac hemodynamics could be an important contributor in the mechanism of dyspnea in patients with large pleural effusion.     

Induction of cell proliferation, micronuclei and hyperdiploidy/polyploidy in the mammary cells of DDT- and DMBA-treated pubertal rats

The environmental estrogen, dichlorodiphenyltrichloroethane (DDT), and its metabolites have been implicated in the development of breast cancer through mechanisms that remain to be elucidated. It has been hypothesized that exposure to DDT and its metabolites, during critical periods of development, can contribute to an elevated risk for breast cancer in adults. In the present study, we have investigated the effect of o,p'-DDT on mammary gland cell proliferation and chromosomal alterations, in a rat mammary cancer model (commonly used to study human cancer), to gain insights into its potential role in the development of breast cancer. Twenty-one-day-old female Sprague-Dawley (SD) rats were administered o,p'-DDT, 7,12-dimethylbenz[a]anthracene (DMBA), genistein, DDT+DMBA, or DDT+DMBA+genistein, over a 14-day period. To determine changes in chromosome number and structure, we used the micronucleus assay as well as multicolor fluorescence in situ hybridization (FISH) region-specific DNA probes for rat chromosomes 4 and 19. Cell proliferation was evaluated using 5-bromo-2'-deoxyuridine (BrdU). Significant increases in BrdU-incorporated cells were seen in the rats treated with DDT+DMBA. Although micronucleus frequencies were somewhat elevated in several of the treatment groups, significant increases were not seen in any of them. Significant increases in numerical chromosomal aberrations were detected in all of the DDT- and DMBA-treated groups. Genistein significantly reduced BrdU incorporation and polyploidy in the DDT+DMBA-treated rats. These initial studies indicate that DDT and DMBA can induce cellular and chromosomal alterations in the rat mammary gland, which is consistent with the hypothesis that these agents can induce early events in mammary carcinogenesis.     

GDF 15 - A Novel Biomarker in the Offing for Heart Failure

Background:

Several diagnostic and prognostic biomarkers are being explored in heart failure. GDF-15 belongs to the transforming growth factor β (TGF-β) cytokine family that is highly up regulated in inflammatory conditions. We undertook this systematic review to summarize the current evidence on the utility of GDF-15 as a biomarker in heart failure.

Design and Methods:

Multiple electronic databases for studies that reported the association between GDF- 15 and heart failure were searched using different electronic databases such as MEDLINE, Science Direct, Springer Link, Scopus, Cochrane Reviews, and Google Scholar using pre-defined inclusion- exclusion criteria.

Results:

Twenty one original studies were identified that included data from 20,920 study participants. GDF 15 was found to be a strong prognosticator of all-cause mortality in heart failure patients. Several studies found the benefit of using GDF-15 as a component of a multi-biomarker strategy in prognosticating patients with heart failure.

Conclusion:

More studies are warranted to elucidate the molecular pathways involving GDF-15 and to see how knowledge about GDF-15 can be used to make therapeutic decisions in the clinic.     

Evaluation of hepatoprotective activity of Kyllinga nemoralis (Hutch & Dalz) rhizomes

Aim of study

In view of the use of rhizomes of Kyllinga nemoralis L., against hepatopathy in ethnomedicine the present study was aimed at evaluating the hepatoprotective activity of the rhizomes of Kyllinga nemoralis against carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats.

Materials and methods

Hepatotoxicity was induced in male Wistar rats by carbon tetrachloride and olive oil (50%, v/v). i.p. ethanolic and petroleum ether extracts of Kyllinga nemoralis rhizomes were administered to the experimental rats (100 and 200 mg/kg, p.o. for seven days). The hepatoprotective effect of these extracts was evaluated by the assay of liver function biochemical parameters and histopathological studies of the liver compared with silymarin.

Results

Both extracts showed significant hepatoprotection when compared to control, similar to standard silymarin. Histology of liver sections also revealed that the extracts protected liver from injury.

Conclusions

The study identified a plant with potential hepatoprotective constituents which will be isolated and characterized in future.     

Concussion and the adolescent athlete

Traumatic brain injury (TBI) is a complex and debilitating neurological injury that places a significant financial and emotional burden on both families and medical providers. Accumulating evidence suggests that mild TBI or concussion remains grossly underdiagnosed, as compared with more severe TBI, due to a poor understanding of the clinical signs and symptoms involved with a head injury. Notably, pediatric head injury may be associated with the subsequent development of serious, long-term neurological consequences, emphasizing the need for improved diagnosis and acute medical intervention. The purpose of this minireview is to summarize the association between participation in youth athletics and the occurrence of concussions, a primary source of mild TBI in the adolescent population, with the goal of increasing awareness within the nursing profession for this clinically important yet underdiagnosed form of brain injury.     

Sclerosing cholangitis and intracranial lymphoma in a child with classical Wiskott–Aldrich syndrome

Patients with Wiskott–Aldrich syndrome (WAS) are predisposed to malignancy and autoimmunity in addition to infections. We report a male child with WAS, who had presented with recurrent pneumonia, eczema, thrombocytopenia, autoimmune hemolytic anemia, and vasculitic skin lesions. Genetic analysis revealed a classical genotype WAS 155C>T; R41X. At 2 years of follow‐up, he developed persistent headache and progressive hepatomegaly. Brain imaging showed a mass in the right frontal region, which on histopathology was shown to be high‐grade non‐Hodgkin lymphoma. Magnetic resonance cholangiopancreatography showed features of sclerosing cholangitis. This report extends the clinical spectrum and highlights unusual manifestations of sclerosing cholangitis and intracranial lymphoma in a patient with WAS.     

Dendritic cells primed with HPV positive cervical tumor lysate are superior to unprimed DCs in migratory capacity and induce a potent Th1 response

In this study, we assessed the efficacy of tumor lysate primed and unprimed monocyte derived mature dendritic cells (DCs) to trigger an effective anti-tumor immune response in cervical cancer patients who tested positive for human papilloma virus (HPV) DNA. Lysate primed and unprimed DCs were assessed for the expression of CD80, CD86, CD40, HLADR and CD83. The ability of DCs to migrate in response to the chemokines CCL19 and 21 as well as their ability to secrete IL12p40 was investigated. Mixed lymphocyte proliferation assays were used to assess DC stimulatory capacity and their ability to generate a Th1 response. Our results showed no difference in phenotypic expression between primed and unprimed DCs but both had significantly increased expression of the activation marker CD83 when compared to immature DCs. Importantly, the primed DCs showed significant (P value = 0.03) IL-12p40 secretion and a superior migratory capacity towards CC19 and CCL21 (P value = 0.04) compared to unprimed DCs even after cytokine withdrawal. Primed DCs showed superior stimulation of T cell proliferation (allogeneic and autologous) and secretion of IFN gamma (IFN-γ) than the unprimed DCs. Hence whole tumor lysate primed mature DCs could be potent immunotherapeutic adjuvants to standard treatment for cervical cancer.     

Enhanced ubiquitination of cytoskeletal proteins in pressure overloaded myocardium is accompanied by changes in specific E3 ligases

Ubiquitin conjugation of proteins is critical for cell homeostasis and contributes to both cell survival and death. Here we studied ubiquitination of proteins in pressure overloaded (PO) myocardium in the context of cardiomyocyte survival. Analysis using a feline right ventricular pressure overload (RVPO) model revealed a robust and transient increase in ubiquitination of proteins present in the Triton X-100-insoluble fraction in 24 to 48 h PO myocardium, and confocal micrographs indicate this increase in ubiquitination occurs subsarcolemmaly near the intercalated disc area of cardiomyocytes. The ubiquitination was accompanied by changes in E3 ligases including Cbl, E6AP, Mdm2 and cIAP in the same period of PO, although atrophy-related E3 ligases, MuRF1 and MuRF3 were unaltered. Furthermore, Cbl displayed a substantial increase in both levels of expression and tyrosine phosphorylation in 48 h PO myocardium. Confocal studies revealed enrichment of Cbl at the intercalated discs of 48 h PO cardiomyocytes, as evidenced by its colocalization with N-cadherin. Although apoptosis was observed in 48 h PO myocardium by TUNEL staining, cardiomyocytes showing ubiquitin staining were not positive for TUNEL staining. Furthermore, 48 h PO resulted in the phosphorylation of inhibitor of nuclear factor kappa B (IkappaB), suggesting its ubiquitin-mediated degradation and the nuclear localization of NFkappaB for the expression of specific cell survival factors such as cIAPs. Together these data indicate that increased levels of E3 ligases that regulate cell homeostasis and promote cell survival could ubiquitinate multiple cytoskeletal protein targets and that these events that occur during the early phase of PO may contribute to both cardiomyocyte survival and hypertrophy.