Post-cooling sperm processing can rescue sperm quality of cooled-stored stallion semen.

Poor sperm quality in cooled-shipped semen has been related to subpar fertility in horses. Therefore, this study aimed to evaluate the ability of post-cooling sperm processing to improve sperm parameters of cooled-stored stallion semen for artificial insemination. For all experiments, ejaculates were collected, processed, and diluted in skimmed milk-based (SM) medium and stored at 5 °C/24h. In all experiments an aliquot of unprocessed cooled semen was used as a control. In the first experiment (Exp 1.), cooled-stored semen from 16 stallions (n = 32) was processed by SpermFilter or centrifugation (600×g/10min) and resuspended in an egg yolk-based freezing medium containing permeating cryoprotectants (EY-C) for cryopreservation. Sperm recovery and motility parameters were immediately assessed after sperm resuspension in both groups and compared with unprocessed (Unp) samples. In Exp 2., cooled semen samples from six stallions (n = 18) were processed using SpermFilter and resuspended in SM or EY-C. Motility parameters and plasma membrane integrity were assessed in all groups (Unp, SM, and EY-C). In Exp 3, cooled semen from four stallions (n = 20) was processed by SpermFilter, resuspended in SM, EY-C, or egg yolk-based medium without cryoprotectants (EY-nC); and submitted to a thermoresistance test (37 °C/3h). Motility parameters, plasma membrane integrity and stability, mitochondrial membrane potential, mitochondrial superoxide generation, and DNA fragmentation index were evaluated in all groups. Finally, in Exp 4, 39 estrous cycles of 11 mares were inseminated with unprocessed (n = 6) cooled-stored semen or semen cooled at 5 °C/24h and then processed by SpermFilter and resuspended in SM (n = 5), EY-C (n = 11), EY-nC (n = 11), or centrifuged and resuspended in EY-C (n = 6). Overall, semen processing and resuspension in EY mediums (EY-C and EY-nC) improved sperm parameters compared with those of unprocessed semen (P < 0.05). Centrifugation (91 ± 5 %) recovered more sperm than SpermFilter (84 ± 9 %; P < 0.05). Sperm resuspended in EY-nC maintained better sperm parameters throughout the thermoresistance test than those in the other groups (P < 0.05). The fertility rates were similar between all groups (P > 0.05). In conclusion, processing and resuspension in EY medium can improve sperm parameters in post-cooled-stored stallion semen.

A simple method for purification of Strongyloides venezuelensis eggs from rat faeces.

The aim of this study was to develop a simple method to purify Strongyloides eggs from rat faeces using a sucrose gradient centrifugal-flotation technique. This procedure is simple, rapid and possesses a high efficiency in recovering Strongyloides eggs without faecal detritus in less than one hour, thus eliminating the use of complex apparatus and different chemical substances. The possibility of working with pure and live Strongyloides eggs opens up a wide range of future studies on the biology of this parasite. This study constitutes the first report in the scientific literature on purifying Strongyloides eggs using a sucrose density gradient.

Insulin resistance negatively affects bone quality not quantity: the relationship between bone and adipose tissue.

The present study suggests that insulin resistance has no association with bone quantity, but quality. INTRODUCTION: The literature has contradictory results concerning the influence of insulin resistance on bone. The present study sought to evaluate the association of insulin resistance and adipose tissue with either bone mineral density or the trabecular bone score. METHODS: The study included 56 individuals (36 women and 20 men): age = 46.6 ± 14.2 years, weight = 67.8 ± 10.9 kg, height = 1.65 ± 0.10 m and BMI = 24.8 ± 3.9 kg/m2. The investigational protocol included biochemical determinations and bone assessment by dual X-ray absorptiometry for evaluation of bone mineral density and trabecular bone score. Magnetic resonance was employed to estimate visceral, subcutaneous and bone marrow adipose tissues, as well as intrahepatic lipids. RESULTS: The bone mineral density of the lumbar spine, femoral neck and total hip were not associated with insulin resistance-related parameters [visceral adipose tissue, intrahepatic lipids and homeostatic model assessment of insulin resistance (HOMA-IR)]. In contrast, there was a negative relationship between the trabecular bone score and all these components. The association between the trabecular bone score and HOMA-IR was reinforced after adjustment for age and BMI. Marrow adipose tissue was negatively associated with both bone mineral density and trabecular bone score. CONCLUSIONS: The present study shows that the trabecular bone score is negatively associated with marrow adipose tissue, insulin resistance, visceral adipose tissue and intrahepatic lipid measurements. Additionally, there was a negative relationship between saturated lipids in marrow adipose tissue and the trabecular bone score. These results encourage further studies to investigate the role of the trabecular bone score exam in the clinical evaluation of osteoporosis in conditions of insulin resistance.

Renal developmental disturbances and their long-term consequences in female pups from vitamin D-deficient mothers: involved mechanisms.

The mechanisms involved in kidney disturbances during development, induced by vitamin D3 deficiency in female rats, that persist into adulthood were evaluated in this study. Female offspring from mothers fed normal (control group, n=8) or vitamin D-deficient (Vit.D-, n=10) diets were used. Three-month-old rats had their systolic blood pressure (SBP) measured and their blood and urine sampled to quantify vitamin D3 (Vit.D3), creatinine, Na+, Ca+2 and angiotensin II (ANGII) levels. The kidneys were then removed for nitric oxide (NO) quantification and immunohistochemical studies. Vit.D- pups showed higher SBP and plasma ANGII levels in adulthood (P<0.05) as well as decreased urine osmolality associated with increases in urinary volume (P<0.05). Decreased expression of JG12 (renal cortex and glomeruli) and synaptopodin (glomeruli) as well as reduced renal NO was also observed (P<0.05). These findings showed that renal disturbances in development in pups from Vit.D- mothers observed in adulthood may be related to the development of angiogenesis, NO and ANGII alterations.

Salivary proteomics in lichen planus: A relationship with pathogenesis?

OBJECTIVES: Oral lichen planus is a chronic, T-cell-mediated, inflammatory disease that affects the oral cavity. The oral lichen planus pathogenesis is still unclear, however, the main evidence is that the mechanisms of activation of different T lymphocyte pathway induce apoptosis with an increase in Th1 and Th17 subtypes cells, triggered by the release of cytokines. This study analysed saliva proteomics to identify protein markers that might be involved in the pathogenesis and development of the disease. MATERIAL AND METHODS: Proteins differentially expressed by oral lichen planus and healthy controls were screened using mass spectrometry; the proteins found in oral lichen planus were subjected to bioinformatics analysis, including gene ontology and string networks analysis. The multiplex analysis validation allowed the correlation between the proteins identified and the involved cytokines in Th17 response. RESULTS: One hundred and eight proteins were identified in oral lichen planus, of which 17 proteins showed a high interaction between them and indicated an association with the disease. Expression of these proteins was correlated with the triggering of cytokines, more specifically the Th17 cells. CONCLUSION: Proteins, such as S100A8, S100A9, haptoglobin, can trigger cytokines and might be associated with a pathological function and antioxidant activities in oral lichen planus.

Relationship between Hammett's parameters and in silico density functional with tandem mass ESI-CID fragmentation: Dihydropyridines as prototypes.

Over the years, with the instrumental analysis evolution, the relationships between the carried-out results with the data of theoretical analysis in silico and the Hammett's parameters have been reported. They have been very useful for chemical characterization of small organic molecules. Thus, this work aims at showing the feasibility and limitations for Hammett's and density functional theory applications in electrospray ionization-collision-induced dissociation (ESI-CID) fragmentation provision. For this, 13 dihydropyrimidinones para, meta, and orto monosubstituted were studied using ESI and CID in positive mode. As a result, it was observed that the main fragmentation includes the isocyanate and ethanol loses at low energy. Nevertheless, at higher energies, radical ions formed by McLafferty rearrangement were observed. The Hammett plots were correlated fragmentation profiles, showing good linearity for the [M + H]+ , which does not occur to radical ions and carbocation's. These tendencies had demonstrated that the stability of protonate and activation energy of secondary ions changes with the pKa. The density functional theory studies indicated that, both nitrogen atoms in the dihydropyrimidinone's prototypes are capable of being protonated. However, the activation energy of fragmentation products is not changed. Therefore, this work has shown information, which can be useful to understand tandem mass spectrometry in ESI-CID conditions for small organic molecules series. This is the first step for normalization of fragmentation pathway.

Reduced bone mass and preserved marrow adipose tissue in patients with inflammatory bowel diseases in long-term remission.

Bone marrow adipose tissue has not been studied in patients with inactive inflammatory bowel disease. We found that these patients have preserved marrow adiposity even with low bone mass. Factors involved in bone loss in active disease may have long-lasting effects but do not seem to affect bone marrow adiposity. INTRODUCTION: Reduced bone mass is known to occur at varying prevalence in patients with inflammatory bowel diseases (IBD) because of inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in these patients as the result of an imbalanced relationship between osteoblasts and adipocytes in bone marrow. This study aimed to evaluate for the first time bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD patients characterized by long-term, steroid-free remission. METHODS: Patients with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment. RESULTS: Both the CD and UC subgroups showed significantly higher proportions of patients than controls with Z-score ≤-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%; p = 0.02), but not at other sites. The proportions of CD patients with a T-score ˂-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C 16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There were no statistically significant differences between IBD patients and controls regarding BMAT at L3 (C 28.62 ± 8.15%; CD 29.81 ± 6.90%; UC 27.35 ± 9.80%; p = 0.67). CONCLUSIONS: IBD patients in long-term, steroid-free remission may have a low bone mass in spite of preserved BMAT. These findings confirm the heterogeneity of bone disorders in IBD and may indicate that factors involved in bone loss in active disease may have long-lasting effects on these patients.

Jumping exercise preserves bone mineral density and mechanical properties in osteopenic ovariectomized rats even following established osteopenia.

The effects of jump training on bone structure before and after ovariectomy-induced osteopenia in rats were investigated. Jumping exercise induced favorable changes in bone mineral density, bone mechanical properties, and bone formation/resorption markers. This exercise is effective to prevent bone loss after ovariectomy even when osteopenia is already established. INTRODUCTION: The present study investigated the effects of jump training on bone structure before and after ovariectomy-induced osteopenia in 80 10-week-old Wistar rats. METHODS: Forty rats (prevention program) were randomly allocated to one of four equal groups (n = 10): sham-operated sedentary (SHAM-SEDp), ovariectomized (OVX) sedentary (OVX-SEDp), sham-operated exercised (SHAM-EXp), and OVX exercised (OVX-EXp). SHAM-EXp and OVX-EXp animals began training 3 days after surgery. Another 40 rats (treatment program) were randomly allocated into another four groups (n = 10): sham-operated sedentary (SHAM-SEDt), OVX sedentary (OVX-SEDt), sham-operated exercised (SHAM-EXt), and OVX exercised (OVX-EXt). SHAM-EXt and OVX-EXt animals began training 60 days after surgery. The rats in the exercised groups jumped 20 times/day, 5 days/week, to a height of 40 cm for 12 weeks. At the end of the experimental period, serum osteocalcin, follicle-stimulating hormone (FSH) dosage, dual X-ray absorptiometry (DXA), histomorphometry, and biomechanical tests were analyzed. RESULTS: The OVX groups showed higher values of FSH and body weight (p < 0.05). DXA showed that jump training significantly increased bone mineral density of the femur and fifth lumbar vertebra (p < 0.05). The stiffness of the left femur and fifth lumbar vertebra in the exercised groups was greater than that of the sedentary groups (p < 0.05). Ovariectomy induced significant difference in bone volume (BV/TV, percent), trabecular separation (Tb.Sp, micrometer), and trabecular number (Tb.N, per millimeter) (p < 0.05) compared to sham operation. Jump training in the OVX group induced significant differences in BV/TV, Tb.Sp, and Tb.N and decreased osteoblast number per bone perimeter (p < 0.05) compared with OVX nontraining, in the prevention groups. Osteocalcin dosage showed higher values in the exercised groups (p < 0.05). CONCLUSIONS: Jumping exercise induced favorable changes in bone mineral density, bone mechanical properties, and bone formation/resorption markers. Jump training is effective to prevent bone loss after ovariectomy even when osteopenia is already established.

Canonical correlation analysis to identify the semen characteristics used to forecast the freeze survival of Curimba (Prochilodus lineatus) spermatozoa.

　　OBJECTIVE: To identify which sperm characteristics were able to predict more accurately the quality of curimba (Prochilodus lineatus) semen upon freezing using canonical correlation analysis. METHODS: Eleven fish breeders with initial mean weight of 705.21 ± 111 g were used. For cryopreservation, 200 µL of semen were taken from each animal and diluted in the cryoprotectant solution (10% dimethyl sulfoxide and 5% Beltsville Thawing Solution Minitub) in a 1:4 ratio and placed into 0.5-mL straws. Sperm characteristics (motility, sperm abnormalities, total antioxidant activity and lipid peroxidation) were evaluated. A randomized block design with duplicate samples per treatment (fresh and frozen semen) was used. The block factor was the animals, and the experimental unit the ejaculates. Canonical correlation was used to evaluate the association between sperm characteristics of fresh semen and thawed semen. RESULT: There was a significant association (P = 0.10) among the variables measured in fresh semen with the variables measured in thawed semen, and 78.6% of the difference observed in the thawed semen can be attributed to variation of variables measured in fresh semen. Sperm motility, motility duration and antioxidant activity of the thawed semen showed an inverse relationship with those of the fresh semen; whereas the minor sperm abnormalities, major sperm abnormalities and lipid peroxidation showed a direct relationship with those of the fresh semen. Only the rate and motility duration of the thawed semen presented high correlation (-0.63 and -0.73, respectively) with the canonical variable represented by the sperm characteristics of fresh semen. CONCLUSIONS: The rate and motility duration of fresh semen may be used to predict the quality of the thawed sperm in Prochilodus lineatus.

Inflammatory response in chronic degenerative endometritis mares treated with platelet-rich plasma.

Degenerative changes of the endometrium are directly related to age and fertility in mares. Chronic degenerative endometritis (CDE) is correlated with uterine fluid retention and reduced ability to clear uterine inflammation. Recent research in the areas of equine surgery and sports medicine has shown that platelet-rich plasma (PRP) treatment acts as an immunomodulator of the inflammatory response. Therefore, the aim of this study was to determine if the uterine infusion of PRP could modulate the local inflammatory response and modify the intrauterine NO concentrations after artificial insemination (AI) in both normal mares and those with CDE. Thirteen mares with endometrium classified as grade III on the histology (mares with CDE) and eight mares with endometrial histological classification I or II-a normal mares were selected to investigate the effect of PRP therapy. The mares were inseminated with fresh semen in two consecutive cycles in a crossover study design. Thereby, each mare served as its own control and the treatment was performed with intrauterine PRP infusion four hours after AI. The percentage of neutrophils in uterine cytology (CIT, %), uterine fluid accumulation observed on ultrasonography (FLU, mm) and nitric oxide concentration of uterine fluid (NO, µM) were analyzed before and 24 hours after AI. The results reported that mares with CDE (CIT, 68.3 ± 3.27, FLU, 10.7 ± 1.61) have a higher (P < 0.05) intrauterine inflammatory response after AI than normal mares (CIT, 24.4 ± 3.56, FLU, 0), but NO concentrations did not differ (P > 0.05) between categories of mares. In treated cycles with PRP, the intrauterine inflammatory response decrease (P < 0.05) in CDE mares (CDE: CIT, 31.4 ± 6.48, FLU, 5.5 ± 1.28; normal mares: CIT, 13.5 ± 4.31, FLU, 0) when compared with nontreated cycle (CDE: CIT, 68.3 ± 3.27, FLU, 10.7 ± 1.61; NM: CIT, 24.4 ± 3.56, FLU, 0), but did not modify NO concentrations in uterine fluid. Thus, we can conclude that PRP was effective in modulating the exacerbated uterine inflammatory response to semen in mares with CDE but did not reduce NO concentrations in intrauterine fluid.

Outcomes and Mortality in Renal Transplant Recipients Admitted to the Intensive Care Unit.

INTRODUCTION: In the intensive care unit (ICU), mortality is considered higher among renal transplant recipients than among nontransplantation patients. However, data regarding severe complications after kidney transplantation are scarce. MATERIALS AND METHODS: In this study, we evaluated all consecutive renal transplant recipients admitted to our ICU between July 2012 and July 2013 (n = 70), comparing their outcomes with those of a control group of nontransplantation patients admitted during the same period (n = 153). Among the transplant recipients, we compared survivors and nonsurvivors to identify predictors of ICU mortality. RESULTS: The mean age of the transplant recipients was 52 ± 13 years. Of the 70 transplant recipients, 18 (25%) required mechanical ventilation, 28 (40%) required inotropic support, and 27 (39%) required hemodialysis, all of which are factors that worsen the prognosis significantly. Twenty-two (31%) of the transplant recipients died in the ICU and 17 (24%) died within 30 days after ICU discharge, rates similar to those observed for the control group. CONCLUSIONS: We observed similar mortality between recipient and control groups, albeit the mortality was higher in the clinical group. In the multivariate model, the need for mechanical ventilation and the need for hemodialysis were independently associated with mortality.

Proposed ratios and cutoffs for the assessment of lipodystrophy in HIV-seropositive individuals.

OBJECTIVES: To propose objective ratios using anthropometry and dual-energy X-ray absorptiometry (DXA) and to suggest cutoff points for them in order to classify lipodystrophy in male patients. METHODS: It is a cross-sectional study. DXA was applied and anthropometric measurements were performed in 100 men on highly active antiretroviral therapy. Receiver operating characteristic curves were used to propose cutoffs. Individuals were divided in without (lipo-) or with (lipo+) lipodystrophy and their metabolic parameters were compared. RESULTS: The following ratios were proposed: fat mass ratio by DXA (FMR), waist thigh ratio (WTR), waist calf ratio (WCR), and arm to trunk ratio (ATR). The best cutoffs observed for FMR, WTR and ATR were 1.26, 1.74 and 2.08, respectively. Using the proposed cutoff for FMR, we observed worse metabolic profile, with increased tryglicerides, fasting serum glucose and more hypercholesterolemia in the lipo+ group. WTR and ATR showed a significant correlation with FMR. CONCLUSIONS: Anthropometric ratios (WTR/ATR) and FMR can be used to aid the diagnosis of lipodystrophy in order to contribute to a more accurate and earlier diagnosis permitting intervention and even preventing metabolic disturbances.

The osteogenic effects of swimming, jumping, and vibration on the protection of bone quality from disuse bone loss.

We assessed and compared the effects of swimming, jumping, and vibration therapies on the prevention of bone loss because of unloading. Eighty Wistar rats were randomly divided into eight groups: S, permanent hind limb-suspended rats; CON, control rats; S + Swim, unloading interrupted by swimming exercise; S + C(Swim), suspension interrupted by regular weight-bearing with the same duration as in the S + Swim protocol; S + Jump, unloading interrupted by jumping exercise; S + C(Jump), suspension interrupted for regular weight-bearing as in the S + Jump group; S + Vibr, unloading interrupted by vibration; and S + C(Vibr), suspension with interruptions for regular weight-bearing with the same protocol as that used for the S + Vibr rats. At the end of the experiment, the bone mineral density, bone strength, histomorphometric parameters, and serum levels of the bone markers were analyzed. The hind limb-suspended rats exhibited bone quality loss. In contrast, the trained rats showed a significant increase in bone mass, bone strength, bone formation, and serum levels of bone markers compared with the respective controls. Although we did not find a significant difference among the three physical exercises, the osteogenic effect of vibration was slightly lower than that of swimming and jumping. Thus, all physical exercises were efficient in preventing bone loss because of unloading and preserving bone quality.

Resistance to thyroid hormone due to mutations in the THRB gene impairs bone mass and affects calcium and phosphorus homeostasis.

CONTEXT: Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone, which is usually due to mutations in the thyroid hormone receptor ß gene (THRB). Few studies have been conducted to investigate bone and mineral metabolism in RTH. OBJECTIVE: The objective of the study was to evaluate the clinical and biochemical parameters related to bone and mineral metabolism in RTH due to mutations in the THRB gene (RTHß). DESIGN AND PARTICIPANTS: We conducted a cross-sectional study on 14 patients with RTHß (RTHG), eight adults and six children, and 24 control subjects (CG). OUTCOMES: Serum measures included total calcium (TCa), inorganic phosphate (iP), alkaline phosphatase (AP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), osteocalcin (OC), carboxyterminal telopeptide (CTX), and fibroblast growth factor 23 (FGF-23). We estimated the renal threshold phosphate concentration (TmPO4/GFR) and assessed bone mass using dual X-ray absorptiometry. RESULTS: Adults and children with RTH showed higher serum levels of TCa than controls (P=.029 and, P=.018 respectively). However, only children with RTH exhibited lower serum levels of iP than controls (P=.048). FGF-23 was higher in RTHß children (P=.04). RTHß adults had lower whole-body (P=.01) and lumbar spine (P=.01) bone mineral density than control subjects. The same pattern was observed when the results were expressed as Z-scores between groups, with a lower value in RTHG than in CG for the lumbar spine of adults (P=.03). No difference was observed between groups in PTH, 25OHD, AP, OC, and CTX. CONCLUSION: Biochemical abnormalities are seen in children with RTH (Low iP, high FGF23), while high calcium (with normal UCa) is seen in RTH subjects of all ages, and later on, in adult life, low BMD is seen. Considering that the TRα1 isoform is the predominant TR in the skeleton, we hypothesize that probably these patients may exhibit enhanced calcium flux from bone to circulation. Our data represent a challenge for new studies to unveil the control of calcium and phosphorus homeostasis and fracture risk in these patients.

Pneumocystis jirovecii pneumonia with an atypical granulomatous response after kidney transplantation.

Pneumocystis jirovecii pneumonia (PCP) continues to be a leading cause of morbidity and mortality in kidney transplant recipients. Granulomatous PCP is an unusual histological presentation that has been described in a variety of immunosuppressive conditions. Previous studies have demonstrated an association between granulomatous disorders and hypercalcemia, the purported mechanism of which is extrarenal production of 1,25-dihydroxyvitamin D by activated macrophages. Here, we report a case of granulomatous formation in a kidney transplant recipient with PCP who presented with hypercalcemia and suppressed parathyroid hormone, both of which resolved after successful treatment of the pneumonia. In immunocompromised patients, pulmonary infection associated with hypercalcemia should raise the suspicion of PCP and other granulomatous disorders.

De novo thrombotic microangiopathy after kidney transplantation: clinical features, treatment, and long-term patient and graft survival.

INTRODUCTION: Posttransplant thrombotic microangiopathy (TMA)/hemolytic uremic syndrome (HUS) can occur as a recurrent or de novo disease. METHODS: A retrospective single-center observational study was applied in order to examine the incidence and outcomes of de novo TMA/HUS among transplantations performed between 2000 and 2010. Recurrent HUS or antibody-mediated rejections were excluded. RESULTS: Seventeen (1.1%) among 1549 kidney transplant recipients fulfilled criteria for de novo TMA. The mean follow-up was 572 days (range, 69-1769). Maintenance immunosuppression was prednisone, tacrolimus (TAC), and mycophenolic acid in 14 (82%) patients. Mean age at onset was 40 ± 15 years, and serum creatinine was 6.1 ± 4.1 mg/dL. TMA occurred at a median of 25 days (range, 1-1755) after transplantation. Nine (53%) patients developed TMA within 1 month of transplantation and only 12% after 1 year. Clinical features were anemia (hemoglobin < 10 g/dL) in 9 (53%) patients, thrombocytopenia in 7 (41%), and increased lactate dehydrogenase in 12 (70%). Decreased haptoglobin was observed in 64% and schistocytes in 35%. Calcineurin inhibitor (CNI) withdrawal or reduction was the first step in the management of 10/15 (66%) patients, and 6 (35%) received fresh frozen plasma (FFP) and/or plasmapheresis. TAC was successfully reintroduced in six patients after a median of 17 days. Eight (47%) patients needed dialytic support after TMA diagnosis and 75% remained on dialysis. At 4 years of follow-up, death-censored graft survival was worse for TMA group (43.0% versus 85.6%, log-rank = 0.001; hazard ratio = 3.74) and there was no difference in patient survival (53.1% versus 82.2%, log-rank = 0.24). CONCLUSION: De novo TMA after kidney transplantation is a rare but severe condition with poor graft outcomes. This syndrome may not be fully manifested, and clinical suspicion is essential for early diagnosis and treatment, based mainly in CNI withdrawal and FFP infusions and/or plasmapheresis.

Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats.

Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

New insights into osteoporosis: the bone-fat connection.

Osteoporosis and obesity are chronic disorders that are both increasing in prevalence. The pathophysiology of these conditions is multifactorial and includes genetic, environmental and hormonal determinants. Although it has long been considered that these are distinct disorders rarely found in the same individual, emerging evidence from basic and clinical studies support an important interaction between adipose tissue and the skeleton. It is proposed that adiposity may influence bone remodelling through three mechanisms: (i) secretion of cytokines that directly target bone, (ii) production of adipokines that influence the central nervous system thereby changing sympathetic impulses to bone and (iii) paracrine influences on adjacent skeletal cells. Here we focus on the current understanding of bone-fat interactions and the clinical implications of recent studies linking obesity to osteoporosis.

Protective effect of the APOE-e3 allele in Alzheimer’s disease

Although several alleles of susceptibility to Alzheimer’s disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitória, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95 percentCI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46, 95 percentCI = 0.30-0.67; P < 0.0001). This study may provide a new insight into the role of the APOE-e3 allele in the etiology of AD and might help to estabilish a profile of risk for AD in the population from Vitória, ES.

Protective effect of the APOE-e3 allele in Alzheimer's disease.

Although several alleles of susceptibility to Alzheimer's disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitória, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95%CI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46, 95%CI = 0.30-0.67; P < 0.0001). This study may provide a new insight into the role of the APOE-e3 allele in the etiology of AD and might help to establish a profile of risk for AD in the population from Vitória, ES.