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- Stress Responsive Biochemical Anabolic/Catabolic Ratio and Telomere Length in Older Adults. [JOURNAL ARTICLE]
- Biodemography Soc Biol 2014; 60(2):174-184.
It has been hypothesized that chronic psychological stress is associated with shorter telomere length; however, the mechanisms that link stress and telomere length are not well understood. To examine the interplay between biochemical factors related to stress arousal and cellular aging, we investigate the association between anabolic/catabolic (A/C) imbalance and leukocyte telomere length (LTL) in the Social Environment and Biomarkers of Aging Study (SEBAS), conducted in Taiwan (N = 925). SEBAS participants aged 54 and older (mean age 68.3) with values for two anabolic hormones (serum dehydroepiandrosterone sulfate [DHEAS] and insulin growth factor [IGF]-1), four catabolic hormones (cortisol, epinephrine, norepinephrine, and interleukin-6 [IL-6]), and LTL were examined. We found that high IL-6 was associated with short LTL (≤ 0.88 T/S ratio; odds ratio [OR] 1.41, 95% confidence interval [CI] = 1.04-1.92). Neither DHEAS/cortisol nor IGF-1/cortisol ratio was associated with telomere length; however, a high A/C imbalance summary score was associated with greater odds of having a short LTL relative to long LTL (OR 1.19, 95% CI = 1.05-1.35). These results indicate that our A/C imbalance score, defined by several anabolic and catabolic biochemical factors, may be one mechanism through which psychological stress is associated with short LTL and possibly cellular senescence.
- Elastin-Derived Peptides Are New Regulators of Thrombosis. [JOURNAL ARTICLE]
- Arterioscler Thromb Vasc Biol 2014 Oct 23.
Elastin is the major structural extracellular matrix component of the arterial wall that provides the elastic recoil properties and resilience essential for proper vascular function. Elastin-derived peptides (EDP) originating from elastin fragmentation during vascular remodeling have been shown to play an important role in cell physiology and development of cardiovascular diseases. However, their involvement in thrombosis has been unexplored to date. In this study, we investigated the effects of EDP on (1) platelet aggregation and related signaling and (2) thrombus formation. We also characterized the mechanism by which EDP regulate thrombosis.We show that EDP, derived from organo-alkaline hydrolysate of bovine insoluble elastin (kappa-elastin), decrease human platelet aggregation in whole blood induced by weak and strong agonists, such as ADP, epinephrine, arachidonic acid, collagen, TRAP, and U46619. In a mouse whole blood perfusion assay over a collagen matrix, kappa-elastin and VGVAPG, the canonical peptide recognizing the elastin receptor complex, significantly decrease thrombus formation under arterial shear conditions. We confirmed these results in vivo because both kappa-elastin and VGVAPG significantly prolonged the time for complete arteriole occlusion in a mouse model of thrombosis and increased tail bleeding times. Finally, we demonstrate that the regulatory role of EDP on thrombosis relies on platelets that express a functional elastin receptor complex and on the ability of EDP to disrupt plasma von Willebrand factor interaction with collagen.These results highlight the complex nature of the mechanisms governing thrombus formation and reveal an unsuspected regulatory role for circulating EDP in thrombosis.
- Severe Adverse Drug Reaction Following Crotalidae Polyvalent Immune Fab (Ovine) Administration for Copperhead Snakebite. [JOURNAL ARTICLE]
- Ann Pharmacother 2014 Oct 23.
To present the case of a severe anaphylactic/anaphylactoid reaction to Crotalidae Polyvalent Immune Fab (Ovine) in a patient bitten by a copperhead snake.A 68-year-old man presented with progressive envenomation after receiving a copperhead snakebite on each hand. Crotalinae Fab antivenom was administered. While the initial and only dose was partially infusing, the patient developed an adverse drug reaction (ADR) of urticaria and hypotension, which resolved with cessation of the infusion, recurred with resumption of the infusion, and ultimately was completed with supportive care. An additional episode of hypotension, urticaria, and angioedema occurred shortly after antivenom therapy completion. Epinephrine was administered, resolving the reaction with complete patient recovery. The event received a Naranjo score of 10, indicating a definite ADR.Treating copperhead snakebites with antivenom is a matter of debate. Concern over adverse events and cost induce some physicians to manage copperhead bites without antivenom because they are generally milder in severity.As demonstrated in this case, severe ADR can occur with Crotalinae Fab antivenom, and its efficacy for copperhead envenoming needs to be better established via placebo-controlled, randomized trials.
- Reduced thrombosis in Klkb1-/- mice is mediated by increased Mas receptor, prostacyclin, Sirt1 and KLF4 and decreased tissue factor. [JOURNAL ARTICLE]
- Blood 2014 Oct 22.
The precise mechanism for reduced thrombosis in prekallikrein null mice (Klkb1(-/-)) is unknown. Klkb1(-/-) mice have delayed carotid artery occlusion times on the rose bengal and ferric chloride thrombosis models. Klkb1(-/-) plasmas have long activated partial thromboplastin times and defective contact activation-induced thrombin generation that partially corrects upon prolonged incubation. However, in contact activation-induced pulmonary thromboembolism by collagen/epinephrine or long chain polyphosphate, Klkb1(-/-) mice, unlike F12(-/-) mice, do not have survival advantage. Klkb1(-/-) mice have reduced plasma BK levels and renal B2R mRNA. They also have increased expression of the renal receptor Mas and plasma prostacyclin. Increased prostacyclin is associated with elevated aortic vasculoprotective transcription factors Sirt1 and KLF4. Treatment of Klkb1(-/-) mice with the Mas antagonist A-779, COX-2 inhibitor nimesulide, or Sirt1 inhibitor splitomicin lowers plasma prostacyclin and normalizes the arterial thrombosis times. Treatment of normal mice with the Mas agonist AVE0991 reduces thrombosis. Klkb1(-/-) mice have reduced aortic tissue factor (TF) mRNA, antigen and activity. In sum, Klkb1(-/-) mice have a novel mechanism for thrombosis protection in addition to reduced contact activation. This pathway arises when bradykinin delivery to vasculature is compromised and it is mediated by increased receptor Mas, prostacyclin, Sirt1 and KLF4 leading to reduced vascular TF.
- Pathophysiological, cardiovascular and neuroendocrine changes in hypertensive patients during the hemodialysis session. [JOURNAL ARTICLE]
- J Hum Hypertens 2014 Oct 23.
The pathophysiological mechanisms of arterial hypertension during hemodialysis (HD) in patients with end-stage renal disease (ESRD) are still poorly understood. The aim of this study is to investigate physiological, cardiovascular and neuroendocrine changes in patients with ESRD and its correlation with changes in blood pressure (BP) during the HD session. The present study included 21 patients with ESRD undergoing chronic HD treatment. Group A (study) consisted of patients who had BP increase and group B (control) consisted of those who had BP reduction during HD session. Echocardiograms were performed during the HD session to evaluate cardiac output (CO) and systemic vascular resistance (SVR). Before and after the HD session, blood samples were collected to measure brain natriuretic peptide (BNP), catecholamines, endothelin-1 (ET-1), nitric oxide (NO), electrolytes, hematocrit, albumin and nitrogen substances. The mean age of the studied patients was 43±4.9 years, and 54.6% were males. SVR significantly increased in group A (P<0.001). There were no differences in the values of BNP, NO, adrenalin, dopamin and noradrenalin, before and after dialysis, between the two groups. The mean value of ET-1, post HD, was 25.9 pg ml(-1) in group A and 13.3 pg ml(-1) in group B (P=<0.001). Patients with ESRD showed different hemodynamic patterns during the HD session, with significant BP increase in group A, caused by an increase in SVR possibly due to endothelial dysfunction, evidenced by an increase in serum ET-1 levels.Journal of Human Hypertension advance online publication, 23 October 2014; doi:10.1038/jhh.2014.93.
- Postoperative pain after bupivacaine supplementation in mandibular third molar surgery: splint-mouth randomized double blind controlled clinical trial. [JOURNAL ARTICLE]
- Oral Maxillofac Surg 2014 Oct 23.
Efficacy of anesthetic supplementation with bupivacaine to control both pain and the number of analgesics ingested after surgery has been proposed; however, no report was found in the literature regarding supplemental use of bupivacaine. Thus, the aim of this study was to evaluate the clinical efficacy of bupivacaine in appeasing postoperative pain, when used as supplemental anesthesia at the end of surgeries to extract mandibular third molars.Eighty surgeries were performed in 40 healthy ASA I patients of mandibular bilateral, semi-enclosed, and symmetrical third molars, in a randomized, double-blind, placebo-controlled, and split-mouth clinical trial. Two procedures were performed. In one case, a preoperative anesthetic block was performed with bupivacaine (0.5 %) and epinephrine (1:200,000). Supplementation with the same anesthetic composition was used at the end of the surgery (test group). In the second case (control group), the procedure was identical to that used in the test group, but was supplemented in a randomized double-blind trial with saline (placebo), using the split-mouth method. Postoperative pain (measured with a visual analog scale) was the primary variable studied, and analgesic consumption was the secondary variable. Nonparametric analysis of variance (Wilcoxon test) and a two-tailed test to determine the ratio was used. P value was set at 0.05.No statistically significant difference (P > 0.05) was found in the variables studied. An adverse effect related to the anesthetic under study was not observed.There is no appreciable value to the second injection regarding pain and analgesia use, but there was a difference regarding patient acceptance in surgeries of mandibular semi-enclosed and impacted third molars.
- Ultrasound-guided saphenous nerve block - within versus distal to the adductor canal: a proof-of-principle randomized trial. [JOURNAL ARTICLE]
- Can J Anaesth 2014 Oct 22.
Reliable saphenous nerve blockade is a desirable complement to popliteal sciatic nerve blockade for foot and ankle surgery. We compared two promising ultrasound-guided techniques, the supine adductor canal (AC) technique and the prone peri-saphenous branch of the descending genicular artery (Peri-SBDGA) technique, using 8 mL of 2% lidocaine with epinephrine 1:400,000.Following Research Ethics Board approval, we conducted a randomized single-blinded parallel-group trial in 102 patients undergoing foot and ankle surgery at a single centre. The primary endpoint was saphenous nerve ease of visualization (0 = not visible; 1 = visible with difficulty; and 2 = easily visible). Other endpoints included vascular landmark visualization (0 = not visible; 1= visible with colour flow Doppler; 2 = visible without colour flow Doppler), block success, onset, and complications.Ninety-one patients were eligible for analysis. Saphenous nerve visibility was not different between the groups (visibility score = 2: AC group, n = 24/49 [49%] vs Peri-SBDGA group, 20/42 [48%]; P = 1.00). Vascular landmark visibility was better in the AC group than in the Peri-SBDGA group (visibility score = 2: 41/49 [84%] vs 25/42 [60%], respectively; P = 0.018). Block success rates were similar (AC group, 41/49 [84%] vs Peri-SBDGA group, 34/42 [81%]; P = 0.79), as were median [interquartile range] onset times (AC group, 5 [5-10] min vs Peri-SBDGA group, 8 [5-11] min; P = 0.38).In this randomized trial, we found no differences in nerve visibility, block success rate, or onset between the AC and Peri-SBDGA techniques of ultrasound-guided saphenous nerve blockade, although the former technique provided superior vascular landmark visibility. Neither technique produced a sufficiently high success rate to provide reliable surgical anesthesia per se.
- Thrombopathy induced by selective serotonin reuptake inhibitors: a case report. [JOURNAL ARTICLE]
- Ann Biol Clin (Paris) 2014 Oct 1; 72(5):607-611.
We report the case of a 20 years old man presenting two episodes of hematemesis. The patient was known to suffer from depression and was treated with sertraline (Zoloft®) for 6 months at the dosage of 100 mg/day. No endoscopic and radiological abnormality was found. The haemostasis report was normal. Exploration of platelet function was in favor of an abnormality of platelet secretion as evidenced by low epinephrine-induced aggregation, a slightly reduced aggregation for following agonists: TRAP, ADP 5 μM and 10 μM, and a longer latency to collagen. The diagnosis of an acquired platelet disorder was strongly suspected and in particular an acquired platelet disorder induced by selective serotonin reuptake inhibitors that is known to interfere with platelet activation pathways involving serotonin.
- Combined use of clips and nylon snare ("tulip-bundle") as a rescue endoscopic bleeding control in a mallory-weiss syndrome. [Journal Article]
- Case Rep Gastrointest Med 2014.:972765.
Mallory-Weiss syndrome (MWS) accounts for 6-14% of all cases of upper gastrointestinal bleeding. Prognosis of patients with MWS is generally good, with a benign course and rare recurrence of bleeding. However, no strict recommendations exist in regard to the mode of action after a failure of primary endoscopic hemostasis. We report a case of an 83-year-old male with MWS and rebleeding after the initial endoscopic treatment with epinephrine and clips. The final endoscopic control of bleeding was achieved by a combined application of clips and a nylon snare in a "tulip-bundle" fashion. The patient had an uneventful postprocedural clinical course and was discharged from the hospital five days later. To the best of our knowledge, this is the first case report showing the "tulip-bundle" technique as a rescue endoscopic bleeding control in the esophagus.
- Citalopram Overdose: a Fatal Case. [JOURNAL ARTICLE]
- J Med Toxicol 2014 Oct 18.
Citalopram is a selective serotonin reuptake inhibitor (SSRI) with cardiac and neurologic toxicities as well as the potential for serotonin syndrome. In most instances, patients recover fully from toxic ingestions of SSRIs. We describe a fatal case of a citalopram overdose.A 35-year-old woman presented to the emergency department after having witnessed seizures at home. An empty citalopram prescription bottle was located, and an intentional overdose was suspected. At the scene, she was found to be in cardiac arrest with pulseless electrical activity and underwent cardiopulmonary resuscitation, including intravenous epinephrine and bicarbonate. In the emergency department, her physical exam was notable for cough and gag reflexes and movement in all extremities with increased muscle tone and tachycardia. Her initial postresuscitation ECG showed sinus rhythm with QRS 92 ms and QTc 502 ms. Her temperature was initially normal, but she rapidly became febrile to 41.8 °C shortly after admission. She was treated symptomatically and with cyproheptadine for suspected serotonin syndrome (SS) but became increasingly hemodynamically unstable over the next 6 h and then developed torsades des pointes (TdP) progressing to pulseless, wide complex tachycardia. She underwent cardiopulmonary resuscitation (CPR) for approximately 50 min but ultimately expired. Postmortem serum analysis revealed a citalopram concentration of 7300 ng/mL (therapeutic range 9-200 ng/mL) and THC, but no other non-resuscitation drugs or substances.Citalopram overdoses often have only mild to moderate symptoms, particularly with ingestions under 600 mg in adults. However, with higher doses, severe manifestations have been described, including QTc prolongation, TdP, and seizures. Serotonin syndrome has also been described in SSRI overdose, and our patient exhibited signs consistent with SS, including increased muscle tone and autonomic dysregulation. Our patient's serum concentration suggests a massive overdose, with major clinical effects, possible SS, and death.Although most patients recover from citalopram overdose, high-dose ingestions can produce severe effects and fatalities may occur. In this case, it is likely that the patient's delayed presentation also contributed significantly to her death. The clinician must be aware of the potential for large ingestions of citalopram to produce life-threatening effects and monitor closely for the neurologic, cardiovascular, and other manifestations that, in rare cases, can be fatal.