Clinical features and outcomes of acute kidney injury among patients with acute hepatitis A

Background

Although acute hepatitis A is usually self-limited, the clinical manifestations can vary from mild to severe liver dysfunction. However, little is known about risk factors for and outcomes of acute kidney injury (AKI) in acute hepatitis A.

Objectives

To identify the risk factors for and outcomes of AKI in acute hepatitis A.

Study design

We identified 396 patients with acute hepatitis A, which registered between January 2006 and June 2009 at a tertiary care university hospital. Retrospective case-control studies were conducted in order to identify risk factors for AKI.

Results

Thirty patients (7.6%) developed AKI. On multivariate analysis, fulminant hepatitis, leukocytosis, and elevated CRP were independent risk factors for AKI associated with hepatitis A, and higher total bilirubin, leukocytosis, and elevated CRP were independent risk factor for AKI within nonfulminant hepatitis A. Of the 30 patients with AKI, 23 (76.7%) patients fully recovered, 2 patients maintained hemodialysis after hospital discharge and 5 patients died due to hepatic failure without recovery from AKI. Among 20 patients with AKI in nonfulminant subgroup, 19 patients (95%) recovered without hemodialysis.

Conclusions

AKI is not a rare complication of acute hepatitis A and severity of hepatitis and hepatic injury influence the development of AKI in acute hepatitis A.     

Designing new β-lactams: implications from their targets, resistance factors and synthesizing enzymes

Penicillins and cephalosporins are β-lactam antibiotics widely used to treat bacterial infectious diseases. They mainly target the cell wall biosynthesis pathway to inhibit bacterial growth. The targets, known as penicillin-binding proteins, are enzymes involved in the polymerization of glycan chains, cross-linking them during bacterial cell wall formation. However, the dispensation of these antibiotics has been concomitant with increasing incidence of resistance to them. Reportedly, this is due to the evolvement of two resistance mechanisms in the bacterial pathogens. One is the production of β -lactamases that cleave the β -lactam rings of penicillin and cephalosporin antibiotics, rendering them ineffective against the pathogens. Another is the modification of the targets, resulting in their inability to bind β -lactam antibiotics. Nevertheless, β -lactam antibiotics remain clinically relevant due to their high target specificity in bacteria and low toxicity to humans. Thus, to overcome the continuing emergence of resistance in pathogens, more efficacious β -lactams have to be developed and cephalosporins are often preferred over penicillins due to two alkyl sites in the cephalosporin core structure amenable for modification. Transformed β -lactams are expected to have improved antimicrobial spectra and pharmacokinetics. This is illustrated by the development of two cephalosporins, namely ceftobiprole and ceftaroline, which have shown good antimicrobial activities and are currently undergoing clinical trials. This review will discuss computer-aided studies of three enzymes closely related to cephalosporins: (1) its synthesizing enzyme, deacetoxycephalosporin C synthase, (2) its targets, the penicillin-binding proteins, and (3) its degrading enzyme, the β -lactamases, and their implications in the development of new cephalosporins.     

Differential effects of amisulpride and haloperidol on dopamine D2 receptor-mediated signaling in SH-SY5Y cells

Dopamine D₂ receptors (D₂R) are the primary target of antipsychotic drugs and have been shown to regulate Akt/glycogen synthase kinase-3β (GSK-3β) signaling through scaffolding protein β-arrestin 2. Amisulpride, an atypical antipsychotic drug, and haloperidol, a typical antipsychotic drug, are both potent D₂R antagonists, but their therapeutic effects differ. In the present study, we compared the effects of amisulpride and haloperidol on the β-arrestin 2-mediated Akt/GSK-3β pathway in SH-SY5Y cells. To determine whether these drugs affected neuronal morphology in SH-SY5Y cells, we investigated the effects of amisulpride and haloperidol on neurite outgrowth using immunostaining. We examined the effects of these drugs on Akt and GSK-3β and its well-known downstream regulators, cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and Bcl-2 levels using Western blot analysis. Amisulpride, but not haloperidol, was found to enhance neurite outgrowth. Small interfering RNA (siRNA) for β-arrestin 2 knockdown blocked the increase in amisulpride-induced neurite outgrowth. Furthermore, amisulpride increased the levels of Akt and GSK-3β phosphorylation, while haloperidol had no effect. The elevation of Akt phosphorylation induced by amisulpride was reduced by β-arrestin 2 siRNA. Moreover, amisulpride effectively increased the levels of phospho-CREB, BDNF, and Bcl-2. However, haloperidol had no effect on the levels of these proteins. Additionally, wortmannin, a phosphatidylinositol 3-kinase (PI3 K) inhibitor, blocked the stimulatory effect of amisulpride on phosphorylated Akt. Together, these results suggest that regulation of the β-arrestin 2-dependent pathway via blockade of the D₂R in SH-SY5Y cells is one mechanism underlying the neuroprotective effect of amisulpride, but not haloperidol.     

Red Liriope platyphylla contains a large amount of polyphenolic compounds which stimulate insulin secretion and suppress fatty liver formation through the regulation of fatty acid oxidation in OLETF rats

Red Liriope platyphylla (RLP) manufactured by two repeated steps (steaming and drying) stimulates the insulin secretion ability and glucose receptor signaling pathway in an animal model for type I diabetes. This study examined the levels of glucose and lipid metabolism-related factors in a useful animal model for type II diabetes with obesity following RLP treatment for 3 weeks to determine if RLP treatment affects the glucose concentration, insulin secretion and fatty acid oxidation. The following results were obtained: i) RLP contained a large amount of polyphenolic compounds; ii) insulin secretion was induced in RLP-treated OLETF rats, although there were no significant differences in body weight, glucose tolerance test and glucose concentration; iii) the RLP-treated OLETF rats showed a significant increase in adiponectin concentration but the concentration of triglyceride and LDL decreased compared to the vehicle-treated rats; iv) although the abdominal fat mass and adipocyte size did not change with RLP treatment, expression of the adipocyte marker genes and β-oxidation genes in fat tissue was recovered to the level of the LETO rats; v) fatty liver formation was reduced dramatically in the liver of the RLP-treated group compared to the vehicle-treated group; vi) the expression of adipocyte marker genes and the β-oxidation gene in the liver tissue were generally similar to those of the abdominal fat but PPAR-γ showed a reverse pattern in the RLP- and vehicle-treated OLETF rats. These results suggest that RLP may stimulate insulin secretion and a decrease in lipid in serum, and may also suppress fatty liver formation through the regulation of fatty acid oxidation. The data presented here highlight the possibility that RLP can be considered a candidate for the prevention or alleviation of obesity-related diseases.     

Adjunctive memantine therapy for cognitive impairment in chronic schizophrenia: a placebo-controlled pilot study

Objective

To investigate the effects of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, on cognitive impairments in patients with chronic schizophrenia.

Methods

A 12-week, placebo-controlled trial was conducted to determine the effectiveness of memantine as an adjunctive treatment with conventional antipsychotic medications in 26 patients with chronic schizophrenia. The subjects were evaluated with the Korean version of the Mini-Mental State Examination (K-MMSE), the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), and a standard neuropsychological screening test.

Results

Memantine treatment was not associated with significantly improved cognitive test scores compared with the placebo control treatment. An improvement in the scores on the PANSS negative subscale was noted with memantine, but it was not significant.

Conclusion

Adjunctive memantine treatment did not improve cognitive functioning or affect psychopathology in patients with chronic schizophrenia in the present study. Memantine, however, was tolerated well and did not exacerbate positive symptoms in patients with chronic schizophrenia.     

Prognostic significance of different subgroup classifications of critical illness-related corticosteroid insufficiency in patients with septic shock

The purpose of this study was to evaluate the prognostic significance of classification of patients with septic shock into different critical illness-related corticosteroid insufficiency subgroups. A retrospective observational study was conducted in patients with septic shock who underwent a short corticotropin stimulation test within 72 h of the onset of shock. Patients were classified into normal adrenal function (NOM), low basal cortisol (LBC) (basal cortisol, <10 μg/dL), or low Δ cortisol (LDC) (basal cortisol, ≥10 μg/dL; cortisol, <9 μg/dL) groups. A total of 168 septic shock patients were recruited. Forty-two patients (25%) were assigned to the NOM group, 39 (23.2%) to the LBC group, and 87 (51.8%) to the LDC group. All of the patients received hydrocortisone therapy. Patients in the LDC group had significantly higher Simplified Acute Physiology Score 3 (P < 0.001) and Sequential Organ Failure Assessment score (P < 0.001) than did patients in the NOM group. The 28-day mortalities of the NOM, LBC, and LDC groups were 40.5%, 38.5%, and 63.2%, respectively (P = 0.007). Classification into the LDC group significantly increased the odds of 28-day mortality (odds ratio, 2.717; 95% confidence interval, 1.452-5.082; P = 0.002) and remained an independent risk factor for mortality even after controlling for all the other potential risk factors identified (odds ratio, 3.638; 95% confidence interval, 1.418-9.028; P = 0.006). Classification into the LDC group is an independent risk factor for mortality in hydrocortisone-treated septic shock patients.     

Searching for the noninvasive biomarker holy grail: are urine proteomics the answer?

Recently, biobehavioral nursing scientists have focused their attention on the search for biomarkers or biological signatures to identify patients at risk for various health problems and poor disease outcomes. In response to the national impetus for biomarker discovery, the measurement of biological fluids and tissues has become increasingly sophisticated. Urine proteomics, in particular, may hold great promise for biobehavioral focused nursing scientists for examination of symptom-and syndrome-related research questions. Urine proteins are easily accessible secreted proteins that provide direct and indirect windows into bodily functions. Advances in proteomics and biomarker discovery provide new opportunities to conduct research studies with banked and fresh urine to benefit diagnosis, prognosis, and evaluation of outcomes in various disease populations. This article provides a review of proteomics and a rationale for utilizing urine proteomics in biobehavioral research. It addresses as well some of the challenges involved in data collection and sample preparation.