Ischemia Modified Albumin in Normal Pregnancy and Preeclampsia

Objective. Ischemia-modified albumin (IMA) has emerged as a new biomarker of myocardial ischemia. Currently, no information is available on maternal IMA levels during normal and complicated pregnancy. Preeclampsia is associated with ischemia and increased formation of free radicals in the placenta. We therefore hypothesized that production of IMA may occur in women with preeclampsia. Methods. Serum IMA and albumin concentrations were assessed in 12 patients with preeclampsia, 12 normal pregnant controls, and 12 nonpregnant controls. IMA levels were compared between groups and corrected for albumin by multivariate regression analysis. Results. Mean IMA levels were elevated in normal pregnant controls (107.3 U/mL; 95% CI, 102.5 to 112.01), compared with nonpregnant controls (94.5 U/mL; CI, 89.4 to 99.6; p = 0.015). In patients with preeclampsia, IMA levels were similar to those in normal pregnant controls (109.7 U/mL; CI, 102.2 to 117.2; p = 0.65). Also, no difference in IMA levels was observed between women with preeclampsia who delivered small-for-gestational-age (SGA) infants (99.0 U/mL; CI, 87.9 to 110.1; p = 0.13) and women with preeclampsia but without SGA. Conclusion. Serum IMA, which has been advocated as a clinical marker of cardiac ischemia, appears to be elevated during normal pregnancy. We found no significant relationship between IMA levels and preeclampsia, in women with or without SGA infants.     

Time in brace: where are the limits and how can we improve compliance and reduce negative psychosocial impact in patients with scoliosis? A retrospective analysis

Background

Brace treatment for adolescent idiopathic scoliosis (AIS) is generally prescribed for 18–23 hours per day, but the minimal time of brace wear per day to stop progression of AIS is still unclear. Compliance of patients with AIS with brace treatment is reported to be between 27% and 47% of the prescribed time, brace wear especially at school is often described as embarrassing by adolescent patients. It has been reported that a higher rate of compliance leads to a significantly lower rate of curve progression. Theoretically, prescribing brace treatment 16 hours instead of 23 hours per day (patients are allowed to attend school free of their brace) could lead to a higher rate of compliance, and subsequently reduce progression rate of patients with AIS.

The fractionation of adipose tissue procedure to obtain stromal vascular fractions for regenerative purposes

Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be obtained by dissociation of adipose tissue, either enzymatically or mechanical. Enzymatic dissociation procedures are time‐consuming and expensive. Therefore, we developed a new inexpensive mechanical dissociation procedure to obtain the stromal vascular fraction from adipose tissue in a time sparing way, which is directly available for therapeutic injection. This mechanical dissociation procedure is denoted as the fractionation of adipose tissue (FAT) procedure. The FAT procedure was performed in eleven patients. The composition of the FAT‐stromal vascular fraction was characterized by immunohistochemistry. Adipose derived stromal cells isolated from the FAT‐stromal vascular fraction were compared with adipose derived stromal cells isolated from nondissociated adipose tissue (control) for their CD‐surface marker expression, differentiation and colony forming unit capacity. Case reports demonstrated the therapeutic effect of the FAT‐stromal vascular fraction. The FAT‐stromal vascular fraction is an enrichment of extracellular matrix containing a microvasculature and culturable adipose derived stromal cells. Adipose derived stromal cells isolated from FAT‐stromal vascular fraction did not differ from adipose derived stromal cells isolated from the control group in CD‐surface marker expression, differentiation and colony forming unit capacity. The FAT procedure is a rapid effective mechanical dissociation procedure to generate FAT‐stromal vascular fraction ready for injection with all its therapeutic components of adipose tissue: it contains culturable adipose derived stromal cells embedded in their natural supportive extracellular matrix together with the microvasculature.     

Genetic alterations in sporadic renal-cell carcinoma: molecular analyses of tumor suppressor gene harboring chromosomal regions 3p, 5q,and 17p

Summary On a genetic level, renal-cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3 (3p), which suggests the inactivation of a tumor suppressor gene. One tumor suppressor gene at 3p, the von Hippel-Lindau disease gene, is implicated in tumor development of a whole spectrum of hereditary neoplasms, including renal-cell carcinoma. It is not clear whether the same tumor suppressor gene accounts for all, i.e., hereditary and sporadic, renal-cell carcinomas. Analysis of 28 patients with sporadic renal-cell carcinomas for loss of heterozygosity was performed at chromosomal regions that contain known tumor suppressor genes so as to assess their potential involvement during renal tumorigenesis. We focused on chromosome 3p because it contains the von Hippel-Lindau (VHL) disease gene, on 5q because it harbors tumor suppressor genes involved in colorectal carcinoma, and on 17p because it includes a tumor suppressor gene involved in breast, colon, and lung carcinoma. Loss of alleles at 3p affected 96% of the evaluable patients, with frequencies being highest in the VHL region in 3p25-26 and at loci in 3p21. These data confirm the importance of a 3p defect early during tumorigenesis; however, the question as to the existence of a second renal-cell carcinoma gene remains unresolved. Changes at 5q were 53% and those at 17p were 35%, suggesting that these loci may not contribute to the initiation of the disease but rather may represent accumulating genetic defects associated with progression and malignancy.     

Rapid changes in serum, plasma and erythrocyte lipid compositions, and serum transaminase levels during continuous enteral hyperalimentation by carbohydrates alone

Twelve normal men received twice their estimated basal energy requirement by a carbohydrate solution via a nasogastric catheter during 48 hours, followed by a seven-hour fast. Subsequently, in nine of them 0.5 mg epinephrine was given subcutaneously under ongoing fasting. During hyperalimentation, serum triglycerides, phospholipids, total and free cholesterol, phospholipids/free cholesterol ratio, and plasma free fatty acids decreased, whereas the percentage of free cholesterol increased. During fasting and subsequent epinephrine administration triglycerides and free fatty acids rose without reaching basal levels. Plasma and red blood cell (RBC) fatty acid composition already changed from two hours after the start of the feeding. Most markedly, a steady decrease in RBC 18:2c, omega 6, amounting to more than 17% of the basal value at the end of the observation period was found. Neither in plasma, nor in RBC a concomitant appearance of 20:3c, omega 9 was seen. In RBC, the relative amounts of the saturated fatty acids increased, whereas those of monounsaturated and polyunsaturated fatty acids decreased. RBC content of total fatty acids decreased and that of cholesterol increased. The ratios 16:1c, omega 7/16:0 and 18:3c, omega 6/18:2c, omega 6 in plasma, and 20:3c, omega 6/18:2c, omega 6 in plasma and RBC increased, whereas those of 18:1c, omega 7/16:1c, omega 7 and 20:3c, omega 6/18:3c, omega 6 in plasma decreased. After 48 hours feeding serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels were moderately increased and rose further during fasting. Thus, continuous enteral hyperalimentation by carbohydrates alone rapidly induces profound changes in serum-, plasma-, and RBC lipid compositions and serum parameters of hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators

Although androgen receptor (AR)-mediated signaling is central to prostate cancer, the ability to modulate AR signaling states is limited. Here we establish a chemical genomic approach for discovery and target prediction of modulators of cancer phenotypes, as exemplified by AR signaling. We first identify AR activation inhibitors, including a group of structurally related compounds comprising celastrol, gedunin, and derivatives. To develop an in silico approach for target pathway identification, we apply a gene expression-based analysis that classifies HSP90 inhibitors as having similar activity to celastrol and gedunin. Validating this prediction, we demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR. Broadly, this work identifies new modes of HSP90 modulation through a gene expression-based strategy.