Plasma proteomics for the assessment of acute renal transplant rejection.

Renal transplant is the best treatment for patients with chronical kidney disease however acute graft rejection is the major impediment to success in renal transplantation leading to loss of the organ the first year after transplantation. The aim of this study was to identify plasma proteins that may be early biomarkers of acute rejection of renal allograft, developing a diagnostic model that avoids the loss of the transplanted organ. Shotgun proteomics (LC-MS/MS) method was used to analyze a set of thirty-one plasma samples, including 06 from patients with acute graft rejection after transplantation (rejection group/Rej-group) and twenty-five from renal transplant patients with stable renal graft function (control group/Ct-group). As results nineteen proteins were upregulated in the rejection group compared to the control group, and two proteins were downregulated; and three were present exclusively in the rejection group. After analysis, we selected four proteins that were related to the acute phase response and that were strongly associated with each other: they are alpha-1 antitrypsin (A1AT), alpha-2 antiplasmin (A2AP), serum amyloid A (SAA) and apolipoprotein CIII (APOC3). We think that simultaneous monitoring of SAA and APOC3 can provide insights into a broad profile of signaling proteins and is highly valuable for the early detection of a possible acute renal graft rejection. STATEMENT OF SIGNIFICANCE OF THE STUDY: In this study we did plasma shotgun patients with and without acute rejection of renal allograft. In a clinical setting an acute rejection is typically suspected upon an increase in plasma creatinine and renal biopsy. But these methods are late and unspecific; sometimes the rejection process is already advanced when there is an increase in serum creatinine. Therefore, it is necessary to find proteins that can predict the allograft rejection process. In our study were able to identify changes in the concentration of plasma protein belonging to a network of protein interaction processes the acute phase response. We believe, therefore, that development of a routine diagnosis of these proteins can detect early acute rejection of renal allograft process, thus preventing its loss.

Clinical relevance of diagnostic hysteroscopy with concurrent endometrial biopsy in the accurate assessment of intrauterine alterations.

PURPOSE: The aim of this retrospective observational study was to evaluate the reliability of diagnostic hysteroscopy, routinely performed along with endometrial biopsy, by analyzing and comparing both hysteroscopic and histopathological outcomes in asymptomatic infertile patients, previously to their IVF cycle. METHODS: The study included 84 consecutive infertile patients who underwent diagnostic hysteroscopy followed by endometrial biopsy. Four-micrometer sections were stained with hematoxylin and eosin and examined microscopically. The data evaluated the frequency and characteristics of endometrial abnormalities found in the biopsies of patients with normal hysteroscopy outcome. Descriptive data are presented as percentages, and the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of hysteroscopy for diagnosis of endometrial alterations were calculated on the basis of pathologic reports. RESULTS: The hysteroscopy evaluation showed 50.0 % of patients with a normal uterine cavity, 40.5 % with endometrial polyps, 6.0 % with endometrial hyperemia, and 3.5 % with other endometrial abnormalities. Among the 42 patients with a normal uterine cavity at hysteroscopic examination, 60.0 % also had a normal biopsy outcome, but in other 40.0 % of patients at least one histopathological abnormal aspect was diagnosed at biopsy. The sensitivity (67.3 %), specificity (80.6 %), PPV (85.4 %) and NPV (59.5 %) of diagnostic hysteroscopy were calculated on the basis of histopathological findings. CONCLUSIONS: Our results show that diagnostic hysteroscopy demonstrated intrauterine alterations in half of infertile patients; histopathological endometrial alterations suggest high rate of false-negative outcomes. Therefore, diagnostic hysteroscopy and concurrent endometrial biopsy should be used as complementary diagnostic and therapeutic approach, especially for patients with previous IVF failures.

Cardiovascular autonomic dysfunction in non-obese diabetic mice.

It is known that diabetes is associated with autonomic dysfunction; however, data about autonomic function in non-obese diabetic mice (NOD) remain scarce. We evaluated the autonomic profile of NOD mice. Female mice, 24-28 week old, were divided in two groups: NOD (n = 6) and control (n = 6, Swiss mice). NOD mice with glycemia ≥ 300 mg/dl were used. Heart rate variability (HRV) and arterial pressure variability (APV) in time and frequency domains, symbolic analysis of heart rate (HR) and baroreflex sensitivity were evaluated. HR and arterial pressure (AP) were similar between the groups; however, HRV (total variance of RR interval: NOD=21.07 ± 3.75 vs. C = 42.02 ± 6.54 ms(2)) and the vagal modulation index RMSSD were lower in NOD group (4.01 ± 0.32 vs. 8.28 ± 0.97 ms). Moreover, the absolute and normalized low-frequency (LF) components were also enhanced in NOD (normalized = 61.0 ± 4.0%) as compared to control mice (normalized = 20.0 ± 4.0%). Both the absolute and normalized high-frequency (HF) components were lower in NOD (normalized = 39.0 ± 4.0%) when compared to the control group (normalized = 80.0 ± 4.0). In the symbolic analysis the 0V pattern, an indication of sympathetic activity, was higher in NOD and 2 LV pattern, an indication of parasympathetic activity, was lower in the NOD than in the control group. Both bradycardic and tachycardic responses were decreased in NOD (3.01 ± 0.72 vs. 4.54 ± 0.36 bpm/mmHg and 2.49 ± 0.31 vs. C = 3.43 ± 0.33 bpm/mmHg) when compared to the control group. Correlation analysis showed negative correlations between vagal indexes (RMSSD, %HF and 2LV) and glycemic levels. In conclusion, NOD mice develop severe diabetes correlated with autonomic dysfunction.