Sagittal split ramus osteotomy-related biomechanical properties.

Sagittal split ramus osteotomy (SSRO) is one of the most common maxillofacial operations, and the technique relies on a directed fracture involving different biomechanical variables. The aim of this study was to find out the biomechanical characteristics involved during each step of sagittal split osteotomy. We sampled eight fully dentate human mandibles and used the right side for hardness tests and the left side for a traction-to-fracture test within an unfinished SSRO. Right sides were sampled in five parts underlying the corticotomy course and tested with a hardness testing automatic machine. The mean hardness measures ranked to 21.5HV (Hardness Vickers Unit): 17.8HV; 27.4HV; 22.7HV; 28.7HV; for the lingual, diagonal, vestibular, full ramus, and full body samples, respectively. Left sides were cut using Epker's technique, and split with an electromechanical testing machine. The higher values reached before fracture in the traction-to-fracture tests ranked to 99.1N/6.7mm; 137.2N/10.8mm; 36.2N/4.2mm; 93.0N/7.3mm; 74.0N/8.1mm; 78.1N/4.5mm; 90.9N/10.6mm; and 64.7N/4.1mm, respectively, for specimens I, II, III, IV, V, VI, VII and VIII. This study provides to our knowledge the first biomechanical characteristics of SSRO and proposes a reproducible method for evaluation.

Implanted Dental Pulp Cells Fail to Induce Regeneration in Partial Pulpotomies.

Cell-based partial pulp regeneration is one of the promising approaches to obtain newly formed functional dentin-pulp complex. It relies on the preservation of the healthy tissue while regenerating the damaged pulp. The aim of this study was to investigate whether this regenerative process could be achieved by implanting porcine dental pulp cells (pDPCs) in pulp defects in the minipig. By split-mouth model, self-assembling injectable nanopeptide hydrogel, with and without pDPCs, was implanted after cameral pulpotomy in premolars and molars. At day 21 after surgery, 3-dimensional morphometric characterization, Masson's trichrome staining, and immunolabeling for DSP and BSP (dentin sialoprotein and bone sialoprotein) were performed on treated teeth. This study demonstrated no pulp regeneration but systematic reparative dentinogenesis. In fact, regardless of the presence of pDPCs in the scaffold, an osteodentin bridge-the microarchitecture of which significantly differed from the native dentin-was systematically obtained. Furthermore, the presence of pDPCs significantly affected the microstructure of the dentin bridges. In the radicular area of each treated tooth, hyperemia in the remaining pulp and external root resorptions were observed. Under the conditions tested in this work, pulp regeneration was not achieved, which highlights the need of further investigations to develop favorable regenerative microenvironment.

Fungemia due to Saprochaete capitata in a non-neutropenic patient hospitalized in an intensive care unit after cardiac surgery.

The majority of invasive fungal infections observed in non-neutropenic patients hospitalized in an intensive care unit are caused by Candida spp and current guidelines recommend echinocandins as the first-line treatment. Fungemias caused by filamentous or arthrosporic fungi such as Saprochaete capitata (previously named Geotrichum capitatum) are extremely rare. In fact, invasive infections due to S. capitata have been reported almost exclusively in neutropenic oncohematological patients. In this report, we describe a case of fungemia caused by S. capitata in a non-neutropenic patient hospitalized in an intensive care unit after aortic valve replacement. The prompt identification of S. capitata is extremely important because of its intrinsic resistance to echinocandins.

[Micro RNA-155 expression in hemodialysis PBMC]. / Espressione del micro rna-155 nelle PBMC di pazienti in emodialisi cronica.

INTRODUCTION: MicroRNAs (miR) are fragments of non-coding RNA acting at post-transcriptional level, which modulate gene expression, and play a key role in several pathophysiological pathways. The aim of this study is to analyze the expression of miR-155 in basal Peripheral Blood Mononuclear Cells (PBMC) of chronic hemodialysis (HD) patients, before and after standard 4 -hour sessions, and after PHA stimulation compared with PBMC from healthy subjects. METHODS: miR-155 was isolated from chronic HD patients' PBMC and from PBMC derived from healthy subjects. Expression levels were quantified with Real-Time PCR; PCR reactions were performed using a specific thermocycler and cycle threshold levels were calculated using dedicated software. Blood samples were taken from HD patients after the long inter-dialytic interval. Data were expressed as MSE and statistical differences were calculated with t-test. RESULTS: Relative quantity (RQ) of pre-dialysis MiR-155 was 3.770.62 times higher than the control group (P=0,003). There was no significant difference before and after hemodialysis sessions. Pre-dialysis mir-155 RQ in PHA PBMC was 1.790.59 times higher than non stimulated PBMC (P=0.019). CONCLUSIONS: these preliminary data show a significant miR-155 up-regulation of HD PBMC when compared to PBMC from healthy individuals. An additional up-regulation was observed in HD PHA PBMC. Similar miR-155 expression was found in HD PBMC comparing pre and post-hemodialysis sessions.

Pretransplant and protocol biopsies may help in defining short and mid-term kidney transplant outcome.

Although many variables may affect long-term graft survival no biomarker is available to identify donor kidney with poor quality and with inadequate short and long-term outcome. While in marginal donors pre-transplant renal biopsies are commonly performed to establish if donor kidneys are suitable for transplantation they are not performed in standard donors. In this study we assessed the relevance of pre-transplant morphological features on post-transplant renal function and evaluated the association between perioperative parameters with posttransplant histological and clinical findings. Kidney transplant recipients undergone pre-transplant and post transplant protocol biopsies at 1, 6, and 12 months were enrolled in the study. Perioperative and posttransplant clinical and biochemical parameters were recorded. Semiquantitative analysis of PAS stained kidney sections was used to determine the degree of lesions. Glomerular volume was measured by computed morphometry. A strong inverse correlation was found between donor age and renal graft function at 1, 6, and 12 months after transplantation. A prompt functional recovery was associated with a better renal function at 6 months and one year. Kidneys with higher glomerular volume demonstrated a lower serum creatinine at 1 month. Higher tubulo-interstitial grading at protocol biopsies was associated with a poor renal function at 1 month. Our findings confirm the importance of donor age in kidney transplant long-term outcome and demonstrate that pretransplant and protocol biopsies are valid options to determine graft outcome and to define therapeutic strategies and tailor immunosuppressive regimen for each patient.

Sirolimus prevents short-term renal changes induced by ischemia-reperfusion injury in rats.

BACKGROUND: Ischemia-reperfusion (I/R) is present at various degrees in kidney transplants. I/R plays a major role in early function and long-term survival of renal allograft. The purpose of our study was to determine if immunosuppressants modulate I/R in a model that separates I/R from all immune responses. METHODS: Sprague-Dawley rats with monolateral renal I/R received daily cyclosporine (A), tacrolimus (B), sirolimus (C) or saline (D). Sham-operated rats received saline (E). After 30 days, glomerular filtration rate for each kidney was measured by inulin clearance. Kidney injury was examined, and TGF-ß, fibronectin and metalloproteases were evaluated by real-time PCR, Western blot and zymography. RESULTS: Sirolimus, but not cyclosporine and tacrolimus, prevented a glomerular filtration rate decrease in I/R kidneys (403 ± 303 vs. 1,006 ± 484 µl/min, p < 0.05; 126 ± 170 vs. 567 ± 374 µl/min, p < 0.05; 633 ± 293 vs. 786 ± 255; A, B and C group, respectively, I/R vs. contralateral kidneys). Sirolimus reduced ED-1+ cell infiltrate, interstitial fibrosis and intimal thickening of small vessels observed in I/R kidneys of controls and calcineurin inhibitor-treated rats. Tacrolimus and cyclosporine increased fibronectin and TGF-ß expression and matrix deposition. Only sirolimus increased metalloprotease activity. CONCLUSIONS: Sirolimus but not calcineurin inhibitors prevented I/R-induced kidney injury.

The epidemic of chronic kidney disease: looking at ageing and cardiovascular disease through kidney-shaped lenses.

In recent years, a 'silent' chronic kidney disease (CKD) epidemic has been proposed by many authors. The 'outbreak' is because of the inclusion of a large proportion of the elderly population within stage 3 CKD according to the Kidney Disease Outcomes Quality Initiative staging system. Unfortunately, this does not take into account the fact that renal function normally declines with age; in addition, the Modification of Diet in Renal Disease formula used to calculate glomerular filtration rate underestimates renal function in the elderly. Because population preventive strategies need a precise definition of the target for screening, a more accurate tool to detect CKD in the general population is required. Considerable interest in CKD has been generated by the evidence that predialysis CKD is associated with increased risk of cardiovascular disease (CVD). Such an association per se does not imply that CKD is a causal determinant of CVD. As CKD has been detected particularly in elderly individuals, it is tempting to speculate that an association may exist between age and cardiovascular outcomes in patients with CKD. Furthermore, the definition of CKD is a nosographic simplification that includes diseases with different causes and pathogenetic mechanisms. The aetiologies of renal diseases can affect cardiovascular outcomes, and the two major causes of end-stage renal disease, diabetes mellitus and hypertension, indeed do so. These findings point to a need for a better definition of CKD to optimize the allocation of healthcare resources and to clarify the nature of the association between CKD and CVD.

Effects of sirolimus on human mesangial cells.

Mesangial cell (MC) proliferation and production of extracellular matrix or loss of MC are both central findings in a number of renal proteinuric diseases. However, the role of MC as components of the glomerular filtration barrier and whether MC alterations induce changes in the glomerular filtration barrier leading to proteinuria are still matters of debate. The effects of Sirolimus (SRL) in proteinuric nephropathies is controversial: some papers have indicated a reduction and others, an increase in proteinuria after sirolimus treatment. Considering the pivotal role of MC in the pathogenesis of many chronic nephropathies, we evaluated the effect of SRL on cultured human MC. We treated primary human MC cultures with SRL, or platelet-derived growth factor (PDGF) or SRL + PDGF, or dimethylsulfoxide, the SRL vehicle, as a control. PDGF was used to activate MC. After 48 hours treatment, MC showed a significant growth increase that was significantly reduced by SRL (P < .01). Apoptosis, determined by the TUNEL assay and flow cytometry, was not modified by the treatments at 24 hours. SRL treatment increased significantly the number of alpha-smooth muscle actin-positive cells compared with controls (P < .05). Cells treated with SRL and SRL + PDGF showed significant changes in morphology with increased mean cell surface, perimeter, and maximum diameter (P < .01) but not protein content. Furthermore, MC treated with SRL showed decreased migration through polycarbonate membranes. The changes induced by SRL may help to explain some of the in vivo effects observed in SRL-treated patients.

Increased asymmetric dimethylarginine serum levels are associated with acute rejection in kidney transplant recipients.

Asymmetric dimethylarginine (ADMA) has been identified as a marker of endothelial dysfunction and an independent risk factor for cardiovascular events in uremic subjects. This study evaluated ADMA plasma levels in kidney transplant recipients. ADMA levels were serially measured during the first year posttransplantation in 41 recipients treated with cyclosporine regimen (CY), sirolimus (SIR), or low-dose cyclosporine plus everolimus (E). Homocysteine, C reactive protein (CRP), nitric oxide (NO), and standard routine laboratory analyses were determined serially. ADMA significantly increased at 6 months posttransplantation, but was significantly lower among patients on SIR or E. NO was only slightly reduced in patients with increased ADMA levels. Interestingly, ADMA was significantly increased during the first 4 days posttransplantation in patients who experienced acute rejection during the first 6 months after transplantation. The same group of patients demonstrated higher levels of CRP and systolic blood pressure before transplantation. Our results demonstrated that ADMA was increased in patients on CY at 6 months. When increased soon after transplantation ADMA may be associated with episodes of acute rejection in kidney transplant recipients. The presence of elevated systolic blood pressure, as well as CRP and ADMA levels, suggested a role for endothelial dysfunction in the development of acute rejection episodes among deceased donor kidney transplant recipients.

The improvement of ischemia/reperfusion injury by erythropoetin is not mediated through bone marrow cell recruitment in rats.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure in kidney transplantation; however, the mechanisms of kidney damage and repair are not yet clear. So far no treatment has been effective to prevent I/R injury. In the present study we evaluated the effect of erythropoetin (EPO) in I/R injury in rats. We investigated the role of bone marrow cells (BMC) in kidney repair and the effect of EPO on BMC recruitment. MATERIALS AND METHODS: Female Sprague Dawley rats transplanted with male BMCs underwent I/R injury. In the treatment group rats received 5000 IU of EPO 30 minutes before renal ischemia. At 2 and 4 weeks after I/R, rats were humanely killed and we measured creatinine clearance (glomerular filtration rate [GFR]), proteinuria, and body weight (BW). Renal tissue was harvested for histologic and molecular analysis. Fluorescein in situ hybridization (FISH) and TUNEL were used to determined the presence of male cell chimerism and apoptosis in renal tissue. RESULTS: At 4 weeks after I/R, EPO significantly improved GFR (1.8 +/- 0.2 vs 1.2 +/- 0.14 mL/min; P < .05). No significant differences between EPO and control rats were observed in proteinuria, BW, and hemoglobin levels at 2 and 4 weeks. After death, the kidney showed only minimal tubulointerstitial changes, which were more marked in control rats. FISH analysis demonstrated a low degree of microchimerism, not significantly different between EPO and control rats. Apoptosis decreased between 2 and 4 weeks after I/R, in both EPO and control groups. CONCLUSION: EPO improved GFR and injury at 4 weeks after I/R; however, it did not enhance the recruitment of BMC.

Rapamycin reduces proteinuria and renal damage in the rat remnant kidney model.

Rapamycin is an immunosuppressive drug used to prevent acute allograft rejection in solid organ transplantation. It shows less nephrotoxicity than calcineurin inhibitors. We evaluated the effect of rapamycin in rats undergoing 5/6 nephrectomy, a model of proteinuric and progressive renal failure. Fourteen days after surgery rats were randomized either to receive rapamycin or to remain untreated (control). Rats were humanely killed on day 91; serum creatinine, creatinine clearance, and proteinuria were assessed. Renal sections were stained with periodic acid-Schiff to evaluate glomerular volume (Gv), glomerulosclerosis (GS) and tubulointerstitial damage (TIS); we evaluated GS and TIS by Sirius red staining (SR). Epithelial-to-mesenchymal transition (EMT) was assessed by immunohistochemistry. Rapamycin affected neither serum creatinine nor creatinine clearance; it reduced Gv (controls, 5.9 +/- 3.1 x 10(6); rapamycin, 1.3 +/- 0.7 x 10(6) microm(3)) and proteinuria (control, 349 +/- 146; rapamycin, 56 +/- 27 mg/24 h; P < .05); rapamycin ameliorated GS (control, 78 +/- 7; rapamycin, 36 +/- 7%; P < .05; SR: control, 13.2 +/- 3.5; rapamycin, 3.8 +/- 1.0%; P < .05), and TIS (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05; SR: control, 29 +/- 3; rapamycin, 11 +/- 3%; P < .05). Rapamycin reduced alphaSMA (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05), VIM (control, 3.5 +/- 0.6; rapamycin, 1.0 +/- 1.4; P < .05), and CD68(+) cells infiltration (control, 110 +/- 43; rapamycin, 24 +/- 1 cells; P < .05). Rapamycin slows the progression of renal damage in the rat remnant kidney and may represent a novel approach to the treatment of chronic kidney disease.

[Use of Valtrac in digestive surgery. Initial clinical experience]. / L'uso del Valtrac in chirurgia digestiva. Iniziale esperienza clinica.

Stapling instruments are being currently used for digestive or colorectal anastomoses with definite advantages. The authors report their initial clinical experience about BAR utilization to restore intestinal continuity after upper digestive and colorectal resections. The authors have been carried out 20 anastomoses on 18 patients: 11 males and 7 females. Eleven (61.1%) of them were affected with malignant neoplasms and in 9 cases were performed an urgency procedure. The colorectal and jejunal-jejunal anastomoses were performed, respectively, in 8 cases; gastric-jejunal and ileo-colic anastomoses, respectively, in 2. The satisfactory results obtained seem to demonstrate that the biofragmentable anastomotic ring constitutes a "safe" method of bowel junction of the whole digestive apparatus.

[Non-ketosic hyperosmolar hyperglycemic coma. Case reports and therapeutic consideration]. / Il coma iperglicemico iperosmolare non chetosico. Contributo casistico e considerazioni terapeutiche

Non-ketonic hyperosmolar hyperglycaemic coma (N.K.H.H.C.) is by no means uncommon in diabetes. Its picture includes sensorial depression, hyperglycaemia, hyperazotemia, marked dehydration and plasma hyperosmolarity. It is mostly found in elderly subjects with non-serious diabetes. Reference is made to 6 personal cases observed during a period of 14 months. The incidence of N.K.H.H.C. noted during this period was 2.2%; this was higher than that of ketoacidotic coma. Two patients died from hypovolaemic shock and one from septic complications. Three survived the episode. Treatment was based on three main points: high doses of insulin, though less than those employed for equal blood sugar levels in cases of ketoacidotic coma, hypotonic saline solutions, and correction of electrolyte imbalance. It is hoped that improved knowledge of the syndrome and, more particularly, earlier diagnosis and treatment, with lead to a reduction in the ta 50% mortality present associated with the disease.