The cerebral microvasculature of the rat: structure and luminal surface properties during early development

The development of the cerebral microvasculature of the rat was studied during three successive postnatal periods, namely: 1) neonatal period, i.e., 1 to 9 days after birth (capillary sprouting period); 2) myelinization period, i.e., 10 to 20 days; and 3) young adult period, i.e., 2 to 3 months. The survey covered structural aspects and distribution of binding sites for anionic or cationic probes and for albumin-gold complexes on the luminal surface of the microvascular endothelium. The salient results are: a) an extensive development of the endoplasmic reticulum of endothelial cells during the first period (presumably in relation with the production of basement membrane components); b) the high surface density of coated pits and coated vesicles that peaks during the myelinization period; c) the paucity of plasmalemmal vesicle and their differential distribution (their volume density is higher in the endothelium of arterioles than in that of capillaries and venules); d) the existence of an extensive smooth surface tubular system in the cytoplasm of endothelial cells, whose structural connections and functional significance remains to be established; and e) the presence of pericytes with elaborate interactions with endothelia in the early developmental periods. Labeling by perfused tracers indicates an uneven patchy distribution of binding sites for cationic ferritin (generally limited to the plasmalemma proper) and a more even distribution of binding sites for cationic and anionic hemeundecapeptides. Binding patterns did not change during the developmental periods studied. No binding sites were detected for albumin-gold complexes.     

Analyzing the learning curves of a novice and an experienced urologist for transrectal magnetic resonance imaging-ultrasound fusion prostate biopsy

BackgroundThe aim of the current study was to evaluate and compare the learning curves of transrectal magnetic resonance imaging-ultrasound fusion biopsy for two urologists with different backgrounds (Operator 1: experienced, self-trained and Operator 2: novice, trained by a mentor/MRI reading courses).MethodsA cohort of 400 patients who underwent fusion prostate biopsy in our department was analyzed. The learning curves were assessed in terms of overall and clinically significant prostate cancer (PCa) detection rates, percentage of positive biopsy cores/targeted and the percentage of PCa tissue on positive targeted cores.ResultsIncreasing trends were observed for both urologists in terms of all biopsy outcomes during the study time. For the novice urologist, a significant increase was observed for overall PCa detection rate, but not for clinically significant disease (25.44%, P=0.04/15%, P=0.145). Operator 1 showed an increasing diagnosis yield of clinically significant disease up to 104 cases. Similar cancer detection rates were observed when comparing the first and last biopsies performed by both operators. Multivariate analysis adjusted for age, PSA, prostate volume, lesion diameter and PIRADS score showed an increase of PCa detection with 51% for every 52 biopsies performed (P=0.022).ConclusionsWhen starting with magnetic resonance imaging-ultrasound fusion prostate biopsy, mentoring and prostate magnetic resonance imaging reading training allow a novice urologist to demonstrate a good initial PCa detection rate. After about 52 cases, he reached a stable PCa and clinically significant PCa detection rate, that was similar to that of an experienced urologist.     

Cardiomyocytes express albumin binding proteins.

We investigated whether cardiomyocytes express specific albumin binding proteins (ABP) which may function in the dissociation of fatty acids from their non-covalent complexes with albumin. The experiments were performed on rat neonatal cardiomyocytes (freshly isolated and up to 3 days in culture) and on an enriched sarcolemmal fraction isolated from adult rabbit ventricular myocardium. Three types of experiments were conducted: (a) identification of ABP on electroblots of cardiomyocytes and sarcolemmal extracts reacted with [125I]-bovine serum albumin ([125I]Alb); (b) kinetic assays of [125I]Alb interaction with cardiomyocytes (at 37 degrees C), and with a sarcolemmal fraction (at 4 degrees C); (c) affinity isolation of ABP from solubilized radioiodinated sarcolemmal proteins interacted with an albumin-agarose matrix. The investigation showed that: first, two pairs of polypeptides (ABP of M(r) 18 and 31 kDa) in either cardiomyocytes or sarcolemmal fraction reacted on electroblots with [125I]Alb; second, the binding of the latter to cardiomyocytes was saturable and competed by unlabeled albumin: 50 microM albumin reduced by approximately 90% the binding of radiolabeled albumin. The sarcolemmal fraction bound [125I]Alb with a Kd of 3.66 x 10(-7) M. Thirdly, among the sarcolemmal proteins retained by the albumin-agarose matrix (18 and 31 kDa), the most prominent was the lower band (approximately 16 kDa) of the 18 kDa pair of ABP. The observations revealed that albumin interacts with relatively high affinity with specific binding sites on cardiomyocyte sarcolemma. This interaction may be a recognition step for subsequent fatty acid dissociation and translocation.     

Advances and perspectives in the genetics of inflammatory bowel diseases.

Several clinical and biological phenotypes define complex diseases such as inflammatory bowel disease (IBD). There is a critical role of the caspase recruitment domain protein 15/nucleotide-binding oligomerization protein 2-dependent (CARD15-NOD2) sensing of bacterial cell wall components in health and disease. The current etiologic model for IBD emphasizes an interaction between susceptibility and modifier genes along with environmental factors. Together, these lead to disease progression. However, further work should clarify the pathophysiological mechanisms leading to IBD and how innate immune signaling confers susceptibility to intestinal inflammation. This is a prerequisite for rational clinical management of IBD. Genetic, functional, serologic testing and development of therapeutics in IBD are discussed.     

WNT Signaling and Cartilage: Of Mice and Men

In adult articular cartilage, the extracellular matrix is maintained by a balance between the degradation and the synthesis of matrix components. Chondrocytes that sparsely reside in the matrix and rarely proliferate are the key cellular mediators for cartilage homeostasis. There are indications for the involvement of the WNT signaling pathway in maintaining articular cartilage. Various WNTs are involved in the subsequent stages of chondrocyte differentiation during development, and deregulation of WNT signaling was observed in cartilage degeneration. Even though gene expression and protein synthesis can be activated upon injury, articular cartilage has a limited ability of self-repair and efforts to regenerate articular cartilage have so far not been successful. Because WNT signaling was found to be involved in the development and maintenance of cartilage as well as in the degeneration of cartilage, interfering with this pathway might contribute to improving cartilage regeneration. However, most of the studies on elucidating the role of WNT signaling in these processes were conducted using in vitro or in vivo animal models. Discrepancies have been found in the role of WNT signaling between chondrocytes of mouse and human origin, and extrapolation of results from mouse models to the human situation remains a challenge. Elucidation of detailed WNT signaling functions will provide knowledge to improve cartilage regeneration.     

Grading of complications and risk factor evaluation in laparoscopic colorectal surgery

Background

A grading system for postoperative complications is important for quality control and comparison among investigations. The objective of the current study was to evaluate complications associated with laparoscopic colorectal surgery according to a standardized grading system, and to examine risk factors associated with different complication grades.

Methods

Data of all patients who underwent elective laparoscopic colorectal surgery at two medical centers between September 2003 and January 2011 were collected prospectively. Complications were graded retrospectively into five categories based on a previously proposed grading system for colorectal operations. Age, gender, BMI, Charlson comorbidity score, indication for surgery, pathology site, conversion rate, learning curve, operative times, previous abdominal surgery, concurrent surgical procedures performed, and length of hospital stay were evaluated as risk factors and outcome measures for complications.

Results

A total of 501 patients were included in the study. Of them, 30.5 % suffered at least one complication and 6.5 % more than one. Complications that were mainly medical or surgical site infections requiring minor intervention (grades 1 and 2) occurred in 22.9 % of patients. Surgical complications requiring invasive interference (grades 3 and 4) occurred in 7.4 % of patients and mortality (grade 5) occurred in 0.2 % (1 patient). Length of hospital stay was directly related to complication grade. Average hospital stay was 6.8 ± 3.5, 10.5 ± 5.1, and 20.2 ± 12.3 days for patients with no complications, grade 1–2 complications, and grade 3–4 complications, respectively (p < 0.01). Minor complications (grades 1–2) were associated with conversion (p < 0.01), high Charlson score (p = 0.004), and additional surgical procedures (p = 0.04). Major complications (grades 3–4) were associated solely with conversion (p < 0.01) and rectal pathology (p < 0.01).

Conclusion

This study demonstrates the use of a uniform grading system for complications in laparoscopic colorectal surgery. Conversion was found to be associated with all grades of complications.