Differences in cerebral oxygenation during exercise in patients with idiopathic pulmonary fibrosis with and without exertional hypoxemia: does exercise intensity matter?

INTRODUCTION AND OBJECTIVES: Patients with idiopathic pulmonary fibrosis (IPF) present respiratory derangements at rest and during exercise, accompanied by exercise intolerance. Some patients may develop profound exertional desaturation even without resting hypoxemia. Evidence suggests the involvement of reduced cerebral-oxygenation in exercise intolerance. We aimed to examine (i) differences in cerebral-oxygenation during exercise between IPF patients with and without isolated exertional desaturation, (ii) whether the impairments in cerebral-oxygenation are detected at similar exercise intensity, and (iii) correlations between cerebral-oxygenation indices, disease severity, and 6-min walk test (6MWT). MATERIALS AND METHODS: Patients with IPF (n = 24; 62.1 ± 9.3 years) without resting hypoxemia underwent cardiopulmonary exercise testing (CPET) with cerebral-oxygenation monitoring via near-infrared-spectroscopy (NIRS). Βased on their pulse-oxymetry saturation (SpO2) during CPET, patients were divided into the "exertional-desaturators" group (SpO2nadir≤89% and ≥6% drop in SpO2) and the "non-exertional-desaturators" group (SpO2nadir≥90% and ≤5% drop). RESULTS: During CPET, the "exertional-desaturators" group exhibited lower oxygenated-hemoglobin (-0.67 ± 1.48 vs. 0.69 ± 1.75 µmol/l; p < 0.05) and higher deoxygenated-hemoglobin (1.67 ± 1.13 vs. 0.17 ± 0.62 µmol/l; p < 0.001) than the "non-exertional-desaturators" group. A different pattern (p < 0.01) in cerebral-oxygenation responses was observed in the two groups. In exertional-desaturators oxygenated-hemoglobin declined below baseline even at low/moderate-intensity exercise (p < 0.05), whereas, in non-exertional-desaturators cerebral-oxygenation declined (p < 0.05) at high-intensity exercise. Cerebral-NIRS indices correlated (p < 0.05) with CPET-duration, dyspnea, diffusion capacity, and 6MWT. CONCLUSIONS: During incremental exercise, patients with IPF and exertional desaturation present a significant decline in cerebral-oxygenation even during low-intensity exercise. Our findings support the implementation of longer-duration rehabilitation programs in IPF so that lower intensity exercise can be applied at the initial stages. (NCT03683082).

Extraperitoneal Spread of Anorectal Abscess: A Case Report and Literature Review.

Supralevator abscess is a rare form of anorectal disease responsible for very rare but morbid manifestations, one of which is superior spread through fascial planes. We present a rare case of a spreading anorectal abscess in a patient who presented with only diffuse abdominal pain, and we review similar cases in the literature according to anatomical considerations, presentation, diagnostic procedures, and treatment options. We identified 7 previously reported cases of spreading anorectal abscesses. Most abscesses had a horseshoe morphology, and all patients presented or developed abdominal pain. All patients had perianal swelling and pain. Five out of 7 patients were previously mistreated. Only 2 abscesses spread through both the pre- and retroperitoneal planes. Abdominal pain is a dominant feature of extraperitoneal inflammation originating from anorectal abscesses. The absence of perianal signs is rare, and proper inspection of the patient along with the medical history can lead to quicker diagnosis and decisive treatment.

Colonization and Infection With Extensively Drug Resistant Gram-Negative Bacteria in Liver Transplant Recipients.

BACKGROUND: Infections due to extensively drug resistant Gram-negative bacteria (GNB) after solid organ transplantation are increasing in prevalence and are associated with high morbidity and mortality. Surveillance culture (SC) seems to be an important tool for extensively drug resistant GNB control. The aim of this study was to evaluate colonization rates and subsequent infections by XDR-GNB in liver transplant recipients. MATERIAL AND METHODS: This was a prospective cohort study in patients who underwent liver transplantation (LT) between January 2016 and January 2018. Data on demographics, extensively drug resistant colonization, and 3-month clinical outcomes were obtained. Colonization was defined as a positive surveillance culture (SC-perirectal) immediately before transplantation, once weekly after LT, and after intensive care unit discharge, with emphasis to carbapenem-resistant Gram-negative bacteria (CR-GNB). RESULTS: Forty-four patients who underwent LT were included in the study. Ten patients (22.72%) were colonized with CR-GNB prior to transplantation, and 7/10 (70%) developed infection due to the same pathogen (5 patients bloodstream infections, 2 patients pneumonia) during the study period. Intensive care unit length of stay was significantly longer in colonized with CR-GNB patients (P < .05). Mortality rate was higher in colonized patients (30%) than in noncolonized (11.76%) (P = .2). CONCLUSION: Our study results suggest an overall 70% risk of CR-GNB infection among colonized patients. Given the high mortality rate and the difficulty in treating these infections, further research to investigate and develop strategies to eliminate the colonization is needed.

Perioperative Chemoprophylaxis οr Treatment for Extensively Drug Resistant Gram-Negative Bacteria in Patients Undergoing Liver Transplantation Based on Preoperative Donor/Recipient Surveillance Cultures: A Prospective Study.

INTRODUCTION: The importance of preoperative donor/recipient colonization or donor infection by extensively drug-resistant Gram-negative bacteria (XDR-GNB) and its relation to serious post-transplantation infection pathogenicity in liver transplantation (LT) patients has not been clarified. AIM: Prevention of postoperative infection due to XDR-GNB with the appropriate perioperative chemoprophylaxis or treatment based on preoperative donor/recipient surveillance cultures in LT patients, as well as their outcome. MATERIALS AND METHOD: Twenty-six patients (20 male, 6 female) were studied (average preoperative Model for End-Stage Liver Disease score ≈15, range: 8-29) from January 2017 to January 2018. In all patients, blood, urine, and bronchial secretions culture samples as well as a rectal colonization culture were taken pre- and postoperatively, once weekly after LT, and after intensive care unit discharge. Recipients with positive XDR-GNB colonization and patients receiving a transplant from a donor with an XDR-GNB positive culture or colonization received the appropriate chemoprophylaxis one half hour preoperatively according to culture results. De-escalation of the antibiotic regimen was done in 2 to 5 days based on the colonization/culture results of the donor and recipient and their clinical condition. Evaluation for serious infection was done at 1 week and at 28 days for outcome results. RESULTS: Fourteen out of 26 recipients (53.8%) were positive for XDR-GNB colonization preoperative, with 2/14 (14.28%) presenting serious infection due to the same pathogen. Intensive care unit length of stay was significantly longer in colonized with XDR-GNB patients (P < .0001). The outcome of colonized patients was 6/14 (42.8%) expired, but only in 2/14 (14.2%) was mortality attributable to infection. CONCLUSION: Administering appropriate perioperative chemoprophylaxis and treatment may limit the frequency of XDR-GNB infections and intensive care unit length of stay and may improve the outcome in LT recipients.

The involvement of phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and MYPT1 isoform expression in NO/cGMP mediated differential vasoregulation of cerebral arteries compared to systemic arteries.

AIM: Constitutive release of NO blunts intrinsic and stimulated contractile activity in cerebral arteries (CA). Here, we explored whether phosphorylation and expression levels of the PKG-sensitive, leucine zipper positive (LZ+ ) splice variants of the regulatory subunit of myosin phosphatase (MYPT1) are involved and whether its expression is associated with higher cGMP sensitivity. METHODS: Vascular contractility was investigated by wire myography. Phosphorylation of MYPT1 was determined by Western blotting. RESULTS: Constitutive phosphorylation of MYPT1-T696 and T853 was lower and that of S695 and S668 was higher in cerebral arteries from the circulus arteriosus (CA-w) than in femoral arteries (FA), while total MYPT1 expression was not different. In CA-w but not in FA, L-NAME lowered phosphorylation of S695/S668 and increased phosphorylation of T696/T853 and of MLC20 -S19, plus basal tone. The increase in basal tone was attenuated in CA-w and basilar arteries (BA) from heterozygous MYPT1-T696A/+ mice. Compared to FA, expression of the LZ+ -isoform was ~2-fold higher in CA-w coincident with a higher sensitivity to DEA-NONOate, cinaciguat and Y27632 in BA and 8-Br-cGMP (1 µmol/L) in pre-constricted (pCa 6.1) α-toxin permeabilized CAs. In contrast, 6-Bnz-cAMP (10 µmol/L) relaxed BA and FA similarly by ~80%. CONCLUSION: Our results indicate that (i) regulation of the intrinsic contractile activity in CA involves phosphorylation of MYPT1 at T696 and S695/S668, (ii) the higher NO/cGMP/PKG sensitivity of CAs can be ascribed to the higher expression level of the LZ+ -MYPT1 isoform and (iii) relaxation by cAMP/PKA pathway is less dependent on the expression level of the LZ+ splice variants of MYPT1.

Serum free ß-human chorionic gonadotropin in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

OBJECTIVE: To define the contribution of maternal variables which influence the measured level of maternal serum free ß-human chorionic gonadotropin (ß-hCG) in screening for pregnancy complications. METHODS: Maternal characteristics and medical history were recorded and serum free ß-hCG was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of free ß-hCG were determined from a linear mixed-effects multiple regression. RESULTS: Serum free ß-hCG was measured in 94 985 cases in the first trimester, 7879 in the second trimester and 8424 in the third trimester. Significant independent contributions to serum free ß-hCG were provided by gestational age, maternal weight, age and racial origin, cigarette smoking, method of conception, diabetes mellitus and family history of pre-eclampsia (PE) in the mother of the patient. The effects of some variables were similar and those for others differed in each trimester. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum free ß-hCG and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates both in pregnancies that developed PE and in those without this pregnancy complication. CONCLUSIONS: A model was fitted to express measured serum free ß-hCG across the three trimesters of pregnancy as MoMs after adjusting for variables from maternal characteristics and medical history that affect this measurement.

Serum pregnancy-associated plasma protein-A in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

OBJECTIVE: To define the contribution of maternal variables which influence the measured level of maternal serum pregnancy-associated plasma protein-A (PAPP-A) in screening for pregnancy complications. METHODS: Maternal characteristics and medical history were recorded and serum PAPP-A was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of PAPP-A were determined from a linear mixed-effects multiple regression. RESULTS: Serum PAPP-A was measured in 94,966 cases in the first trimester, 7785 in the second trimester and 8286 in the third trimester. Significant independent contributions to serum PAPP-A were provided by gestational age, maternal weight, height, racial origin, cigarette smoking, diabetes mellitus, method of conception, previous pregnancy with or without pre-eclampsia (PE) and birth-weight Z-score of the neonate in the previous pregnancy. The effects of some variables were similar and those for others differed in the three different trimesters. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum PAPP-A and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed PE and in those without this pregnancy complication. CONCLUSIONS: A model was fitted to express the measured serum PAPP-A across the three trimesters of pregnancy as MoMs, after adjusting for variables from maternal characteristics and medical history that affect this measurement.

Impact of the Model for End-stage Liver Disease (MELD) score on liver transplantation in Greece.

INTRODUCTION: The impact of preoperative Model for End-stage Liver Disease (MELD) score in postoperative mortality remains unclear. The assumption that patients with a higher MELD score will have a higher mortality rate is not confirmed and studies are contradictory. AIM: The study of the clinical course of patients with a higher MELD score and its impact in immediate and later mortality in comparison with patients with a lower MELD score in the only liver transplantation center in Greece. METHOD: We retrospectively studied 71 patients who underwent orthotopic liver transplantation (OLT) in the time period between 1-1-2011 and 31-12-2013. The patients were divided into 2 groups: Group A with a MELD score ≥23 and Group B with a MELD score <23. RESULTS: In the patients with a MELD score ≥23 the duration of mechanical ventilation and length of stay in the ICU were prolonged (P = .013 and .009, respectively), the transfusions were more (P = .005), and the rates of ICU readmissions (22.5% vs 7.31%, P = .001) and infections (42.5% vs 17.5%, P = .011) were higher. Thirty-day mortality did not differ between the 2 groups (P = .420), but there was a statistically significant difference in morbidity and in 180-day mortality. CONCLUSION: The patients with a higher MELD score have more complex pathophysiology. This score seems to affect morbidity and late, but not early, mortality.

Bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae among intensive care unit patients after orthotopic liver transplantation: risk factors for infection and impact of resistance on outcomes.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as an important cause of bloodstream infections in intensive care units (ICUs). The aim of this study was to determine risk factors for bloodstream infections caused by CRKP as well as risk factors for CRKP-associated mortality among ICU patients after orthotopic liver transplantation (LT). METHODS: The study cohort of this observational study comprised 17 ICU patients after LT with CRKP bloodstream infections. The data from these patients were matched with 34 ICU patients (1:2) after LT without CRKP infections. The 2 groups were compared to identify risk factors for development of CRKP infection and risk factors for mortality. RESULTS: Seventeen CRKP bloodstream infections occurred in ICU patients after LT from January 1, 2008, to December 31, 2011. In univariate analysis, primary liver disease and especially hepatitis C virus infection or hepatocellular cancer were significant factors for development of CRKP. Acute Physiology and Chronic Health Evaluation (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score as well as CRKP bloodstream infection were predictors for ICU death (P < .05) in univariate analysis. CONCLUSIONS: CRKP bloodstream infections affect immunocompromised post-transplantation patients more. Bloodstream infections with CRKP along with APACHE and SOFA scores were predictors of death in ICU patients after LT.

Comparison of RIFLE and AKIN criteria in the evaluation of the frequency of acute kidney injury in post-liver transplantation patients.

BACKGROUND: Acute renal dysfunction is presented quite often after orthotopic liver transplantation (LT), with a reported incidence of 12-64%. The "RIFLE" criteria were introduced in 2004 for the definition of acute kidney injury (AKI) in critically ill patients, and a revised definition was proposed in 2007 by the Acute Kidney Injury Network (AKIN), introducing the AKIN criteria. The aim of this study was to record the incidence of AKI in patients after LT by both classifications and to evaluate their prognostic value on mortality. METHODS: We retrospectively evaluated the records of patients with LT over 2 years (2011-2012) and recorded the incidence of AKI as defined by the RIFLE and AKIN criteria. Preoperative and admission severity of disease scores, duration of mechanical ventilation, intensive care unit length of stay, and 30- and 180-day survivals were also recorded. RESULTS: Seventy-one patients were included, with an average age of 51.78 ± 10.3 years. The incidence of AKI according to the RIFLE criteria was 39.43% (Risk, 12.7%; Injury, 12.7%; Failure, 14.1%), whereas according to the AKIN criteria it was 52.1% (stage I, 22.5%; stage II, 7%; stage II 22.55%). AKI, regardless of the classification used, was related to the Model for End-Stage Liver Disease score, the volume of transfusions, the duration of mechanical ventilation, and survival. The presence of AKI was related to higher mortality, which rose proportionally with the severity of AKI as defined by the stages of either the RIFLE or the AKIN criteria. CONCLUSIONS: AKI classifications according to the RIFLE and AKIN criteria are useful tools in the recognition and classification of the severity of renal dysfunction in patients after LT, because they are associated with higher mortality, which rises proportionally with the severity of renal disease.

Tigecycline for treatment of carbapenem-resistant Klebsiella pneumoniae infections after liver transplantation in the intensive care unit: a 3-year study.

BACKGROUND: This 3-year prospective, observational, single-center study was undertaken to describe prescription, microbiology findings, tolerance, and efficacy of tigecycline for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections after liver transplantation in the intensive care unit (ICU). METHODS: All patients after liver transplantation treated with tigecycline for ≥3 days for CRKP infections in our ICU from January 1, 2010, to December 31, 2012, were studied. Patient characteristics, indication of treatment, bacteriology, and ICU mortality were collected. The main end points were clinical and microbiologic efficacy and tolerance of tigecycline. RESULTS: Over the study period, 8 men and 2 women (18 CRKP isolates), aged 54.3 ± 7.7 years, were included in the study. Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores on ICU admission were 13.7 ± 2.7 and 10 ± 2.2, respectively. In 7 isolates, tigecycline was prescribed for CRKP blood stream infection (BSI), in 6 for complicated intra-abdominal infection (IAI), in 2 for ventilator-associated pneumonia (VAP), in 2 for surgical site infection, and in 1 for urinary tract infection. In 4 cases, tigecycline was prescribed for secondary BSI followed by VAP and/or IAI. All isolates were susceptible to tigecycline, 83.4% to colistin, 44.5% to gentamicin, and 27.8% to amikacin. In 2 patients, tigecycline was prescribed as monotherapy. Three patients had clinical failure. The microbiologic response rate was 70%. Superinfection was detected in 5 patients, and Pseudomonas aeruginosa was the most frequently isolated pathogen. Tigecycline was generally well tolerated. The ICU mortality rate was 60% with attributable mortality rate 30%. CONCLUSIONS: Our pilot study suggests that tigecycline shows a good safety and tolerance profile in patients with CRKP infections in the ICU after orthotopic liver transplantation. Limited therapeutic options for such infections leave physicians no choice but to use tigecycline for off-label indications such as urinary tract and blood stream infections.

Causes and incidence of renal replacement therapy application in orthotopic liver transplantation patients: our experience.

BACKGROUND: Renal dysfunction is commonly found in patients with end-stage liver disease, as well as after liver transplantation, and it often needs renal replacement therapy (RRT) with the application of continuous or intermittent methods. The aim of this study was the recording of the patients who underwent continuous venovenous hemodiafiltration (CVVHDF) in the early postoperative period, as well as the recording of mortality and risk factors. METHODS: We retrospectively examined 71 patients who underwent orthotopic liver transplantation during a 2-year period (2011-2012). We recorded the incidence of acute kidney injury (AKI), according to the Acute Kidney Injury Network criteria, and we distinguished 2 groups of patients. Group A included those who needed RRT during the 1st 7 days after transplantation, and group B included the patients who did not require RRT. The RRT method of choice was CVVHDF. RESULTS: In group A, the population of patients who presented AKI reached 52.1%, and 22.5% of the them underwent RRT. The mean Model for End-Stage Liver Disease and Acute Physiology and Chronic Health Evaluation scores were higher in group A, who also presented greater hemodynamic instability and more frequent infections and required more transfusions. The transfusion of >10 units of red blood cells was recognized as a risk factor for RRT (P = .024; odds ratio, 1.15; 95% confidence interval, 1.8-7.53). CONCLUSIONS: Patients who required RRT immediately after surgery had a significantly higher rate of mortality and it seemed that the number of transfusions played an important role in this.

Fam40b is required for lineage commitment of murine embryonic stem cells.

FAM40B (STRIP2) is a member of the striatin-interacting phosphatase and kinase (STRIPAK) complex that is involved in the regulation of various processes such as cell proliferation and differentiation. Its role for differentiation processes in embryonic stem cells (ESCs) is till now completely unknown. Short hairpin RNA (shRNA)-mediated silencing of Fam40b expression in ESCs and differentiating embryoid bodies (EBs) led to perturbed differentiation to embryonic germ layers and their derivatives including a complete abrogation of cardiomyogenesis. Pluripotency factors such as Nanog, Oct4 and Sox2 as well as epigenetic factors such as histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3-ß (Dnmt3b) were highly upregulated in Fam40b knockdown EBs as compared with control and scrambled EBs. To examine the relevance of Fam40b for development in vivo, Fam40b was knocked down in developing zebrafish. Morpholino-mediated knockdown of Fam40b led to severe abnormalities of the cardiovascular system, including an impaired expression of ventricular myosin heavy chain (vmhc) and of cardiac myosin light chain 2 (cmlc2) in the heart. We identified the gene product of Fam40b in ESCs as a perinuclear and nucleolar protein with a molecular weight of 96 kDa. We conclude that the expression of Fam40b is essential for the lineage commitment of murine embryonic stem cells (mESCs) into differentiated somatic cells via mechanisms involving pluripotency and epigenetic networks.

Differential effects of RGK proteins on L-type channel function in adult mouse skeletal muscle.

Work in heterologous systems has revealed that members of the Rad, Rem, Rem2, Gem/Kir (RGK) family of small GTP-binding proteins profoundly inhibit L-type Ca(2+) channels via three mechanisms: 1), reduction of membrane expression; 2), immobilization of the voltage-sensors; and 3), reduction of Po without impaired voltage-sensor movement. However, the question of which mode is the critical one for inhibition of L-type channels in their native environments persists. To address this conundrum in skeletal muscle, we overexpressed Rad and Rem in flexor digitorum brevis (FDB) fibers via in vivo electroporation and examined the abilities of these two RGK isoforms to modulate the L-type Ca(2+) channel (CaV1.1). We found that Rad and Rem both potently inhibit L-type current in FDB fibers. However, intramembrane charge movement was only reduced in fibers transfected with Rad; charge movement for Rem-expressing fibers was virtually identical to charge movement observed in naïve fibers. This result indicated that Rem supports inhibition solely through a mechanism that allows for translocation of CaV1.1's voltage-sensors, whereas Rad utilizes at least one mode that limits voltage-sensor movement. Because Rad and Rem differ significantly only in their amino-termini, we constructed Rad-Rem chimeras to probe the structural basis for the distinct specificities of Rad- and Rem-mediated inhibition. Using this approach, a chimera composed of the amino-terminus of Rem and the core/carboxyl-terminus of Rad inhibited L-type current without reducing charge movement. Conversely, a chimera having the amino-terminus of Rad fused to the core/carboxyl-terminus of Rem inhibited L-type current with a concurrent reduction in charge movement. Thus, we have identified the amino-termini of Rad and Rem as the structural elements dictating the specific modes of inhibition of CaV1.1.

The effect of Antithrombin-III on routine hematological and biochemical parameters in an experimental animal model of skeletal muscle ischemia-reperfusion injury.

BACKGROUND: Antithrombin III (AT-III) has been shown to attenuate the local and systemic harmful effects of skeletal muscle ischemia-reperfusion (I-R) injury. The aim of the present study was to monitor the fluctuation of routine hematological and biochemical parameters in an experimental animal model of tourniquet-induced skeletal muscle I-R injury and to investigate how these are influenced by the protective administration of AT-III. METHODS: Sixty male Wistar rats were submitted to a 6-hour, tourniquet-induced, complete ischemia of the right hind-limb. Animals were divided into those receiving AT-III (dose, 250 IU/kg) 30 minutes before the reperfusion (group A, n=30) and those receiving placebo (group B, n =30). Another 10 animals were sham-operated (group C). White blood cell (WBC) and platelet (PLT) count, aspartate and alanine aminotransferases (AST and ALT), alkaline phosphatase (ALP), and γ-glutamyl transferase (γ-GT) were estimated in blood samples taken from the inferior vena cava at 3 different time points post-reperfusion (at baseline, at 30 minutes and at 4 hours) and groups A and B were compared using the Mann-Whitney U test. RESULTS: There were no statistically significant differences between the AT-III and the placebo groups at 0, 30 minutes and 4 hours with regard to the WBC, ALT and γ-GT levels, however, there was a significant decrease of AST levels 4 hours post-reperfusion in the AT-III group compared to the placebo group (p=0.002). An increased PLT count and ALP levels 30 minutes post-reperfusion were also noted in the AT-III group compared to placebo (p<0.001; and p=0.001, respectively). CONCLUSIONS: Of the routine hematological and biochemical parameters tested, AST was found to be significantly suppressed at 4 hours in the AT-III-treated animals, suggesting a possible beneficial effect of AT-III in mouse skeletal muscle I-R injury. The effect of AT-III on PLTs and ALP levels merits further investigation. Hippokratia 2014; 18 (3): 234-239.

Potent inhibition of L-type Ca2+ currents by a Rad variant associated with congestive heart failure.

Ca(2+) influx via L-type voltage-gated Ca(2+) channels supports the plateau phase of ventricular action potentials and is the trigger for excitation-contraction (EC) coupling in the myocardium. Rad, a member of the RGK (Rem, Rem2, Rad, Gem/Kir) family of monomeric G proteins, regulates ventricular action potential duration and EC coupling gain through its ability to inhibit cardiac L-type channel activity. In this study, we have investigated the potential dysfunction of a naturally occurring Rad variant (Q66P) that has been associated with congestive heart failure in humans. Specifically, we have tested whether Rad Q66P limits, or even eliminates, the inhibitory actions of Rad on CaV1.2 and CaV1.3, the two L-type channel isoforms known to be expressed in the heart. We have found that mouse Rad Q65P (the murine equivalent of human Rad Q66P) inhibits L-type currents conducted by CaV1.2 or CaV1.3 channels as potently as wild-type Rad (>95% inhibition of both channels). In addition, Rad Q65P attenuates the gating movement of both channels as effectively as wild-type Rad, indicating that the Q65P substitution does not differentially impair any of the three described modes of L-type channel inhibition by RGK proteins. Thus, we conclude that if Rad Q66P contributes to cardiomyopathy, it does so via a mechanism that is not related to its ability to inhibit L-type channel-dependent processes per se. However, our results do not rule out the possibility that decreased expression, mistargeting or altered regulation of Rad Q66P may reduce the RGK protein's efficacy in vivo.

Operative treatment of gynaecologic diseases in puberty: seven years of experience.

PURPOSE OF INVESTIGATION: The aim of this study is to present the incidence and surgical management of gynaecologic pathology in adolescence in the 1st Obstetrics and Gynecology Department of Aristotle University of Thessaloniki. METHODS: After a retrospective review of the medical records of over a seven year period (2004-2011), 32 adolescent patients with reported surgical gynaecologic procedures were identified and analysed. RESULTS: Fourteen out of the 16 adolescents with ovarian masses (eight neoplastic and eight non-neoplastic) were treated by laparoscopy. Congenital anomalies were diagnosed in seven patients and only one of them was treated by laparotomy. The rest were surgically treated for uterine leiomyoma (1), ectopic pregnancy (2), pelvic abscess (1), mesosalpingeal cysts (2), mesenterian cyst (1) and investigation of chronic pelvic pain. DISCUSSION: Although benign ovarian cysts and congenital anomalies represent the major indication for operative treatment of gynaecologic diseases in puberty, laparoscopy and/or hysteroscopy should be the gold standard procedure after careful preoperative investigation.

Reduced metaboreflex control of blood pressure during exercise in individuals with intellectual disability: a possible contributor to exercise intolerance.

The aim was to investigate the hemodynamic responses to isometric handgrip exercise (HG) and examine the role of the muscle metaboreflex in the exercise pressor response in individuals with intellectual disability (IID) and non-disabled control subjects. Eleven males with mild-moderate intellectual disabilities and eleven non-disabled males performed a testing protocol involving 3-min periods of baseline, HG exercise (at 30% MVC), circulatory occlusion, and recovery. The same protocol was repeated without occlusion. At baseline, no differences were detected between groups in beat-to-beat mean arterial pressure (MAP), heart rate (HR), stroke volume, and peripheral resistance. IID were able to sustain an exercise MAP response at comparable levels to the control group exerting similar peripheral resistance; however, IID exhibited a blunted chronotropic response to HG and a diminished exercise vagal withdrawal compared to controls. During occlusion, IID exhibited a lower pressor response than their control peers, associated with a lower increase in peripheral resistance during this task. In conclusion, although intellectual disabilities can be the consequence of many different genes, IID share common deficits in the chronotropic response to exercise and a blunted metaboreflex-induced pressor response.