Carnitine in Alcohol Use Disorders: A Scoping Review

Recent studies in alcohol use disorders (AUDs) have demonstrated some connections between carnitine metabolism and the pathophysiology of the disease. In this scoping review, we aimed to collate and examine existing research available on carnitine metabolism and AUDs and develop hypotheses surrounding the role carnitine may play in AUD. A scoping review method was used to search electronic databases in September 2019. The database search terms used included “alcohol, alcoholism, alcohol abuse, alcohol consumption, alcohol drinking patterns, alcohol-induced disorders, alcoholic intoxication, alcohol-related disorders, binge drinking, Wernicke encephalopathy, acylcarnitine, acetyl-l-carnitine, acetylcarnitine, carnitine and palmitoylcarnitine.” The inclusion criteria included English language, human-based, AUD diagnosis and measured blood or tissue carnitine or used carnitine as a treatment. Of 586 studies that were identified and screened, 65 underwent abstract review, and 41 were fully reviewed. Eighteen studies were ultimately included for analysis. Data were summarized in an electronic data extraction form. We found that there is limited literature available. Alcohol use appears to impact carnitine metabolism, most clearly in the setting of alcoholic cirrhosis. Six studies found carnitine to be increased in AUD, of which 5 were conducted in patients with alcoholic cirrhosis. Only 3 placebo-controlled trials were identified and provide some support for the use of carnitine in AUD to decrease cravings, anhedonia, and withdrawal and improve cognition. The increase in plasma carnitine in alcoholic cirrhosis may be related to disordered fatty acid metabolism and oxidative stress that occurs in AUD. The multiple possible therapeutic effects carnitine could have on ethanol metabolism and the early evidence available for carnitine supplementation as a treatment for AUD provide a foundation for future randomized control trials of carnitine for treating AUD.     

Donor‐specific anti‐HLA antibodies in pediatric renal transplant recipients with creeping creatinine: Prevalence,histological correlations,and impact on patient and graft survival

Donor‐specific anti‐HLA antibodies (DSA) causing CAMR are responsible for a high proportion of long‐term graft failures after RTX. We studied the prevalence of DSA in RTX children biopsied for creeping Cr, its relationship with NA, and patient and graft survival according to histopathology. Between 2008 and 2013, 92 children were biopsied at a median of 38 months post‐RTX. At biopsy, the prevalence of DSA was 49% and C4d 70%. NA rate was 45%, higher in adolescents (60%). Most frequent diagnoses were CAMR (72%) and interstitial fibrosis with tubular atrophy (IFTA) (28%). Forty‐five of 66 patients with CAMR (68%) had detectable DSA. Twenty‐one DSA‐negative patients with CAMR had histological damage (IFTA + C4d positivity). C4d was detected in 64 of 66 biopsies with CAMR. Recipients with IFTA alone had neither C4d, nor detectable DSA, and were adherent. Graft survival at five yr was 89% in patients with CAMR, 79% in those with CAMR + TCMR Banff I, 33% in those with CAMR + TCMR Banff II, and 96% in those with IFTA. ABMR and complement activation were frequent in children biopsied for creeping Cr. Recipients with DSA were more likely to be non‐adherent and have CAMR or CAMR + TCMR and worse graft survival.     

Primary lymphoma of the heart: three-dimensional reconstruction

Primary cardiac lymphoma is defined as a lymphoma of the heart and pericardium with little or no extracardiac or local involvement such as mediastinal lymph nodes or pleural effusion. Most cases are diagnosed only post mortem (1). If this disease could be diagnosed earlier, therapy with chlorpropamide, doxorubicin, vincristine and prednisone (CHOP) could bring about a remission (2,3,4). Transoesophageal echocardiography with three-dimensional acquisition is a new technique which can allow earlier diagnosis, and facilitate guided transvenous biopsy (5,6). We here report an example of the pre-mortem diagnosis of cardiac lymphoma by these techniques.     

Improving residents’ confidence in using psychosocial skills

OBJECTIVE: To evaluate an intensive training program’s effects on residents’ confidence in their ability in, anticipation of positive outcomes from, and personal commitment to psychosocial behaviors. DESIGN: Controlled randomized study. SETTING: A university- and community-based primary care residency training program. PARTICIPANTS: 26 first-year residents in internal medicine and family practice. INTERVENTION: The residents were randomly assigned to a control group or to one-month intensive training centered on psychosocial skills needed in primary care. MEASUREMENTS: Questionnaires measuring knowledge of psychosocial medicine, and self-confidence in, anticipation of positive outcomes from, and personal commitment to five skill areas: psychological sensitivity, emotional sensitivity, management of somatization, and directive and nondirective facilitation of patient communication. RESULTS: The trained residents expressed higher self-confidence in all five areas of psychosocial skill (p<0.03 for all tests), anticipated more positive outcomes for emotional sensitivity (p=0.05), managing somatization (p=0.03), and nondirectively facilitating patient communication (p=0.02), and were more strongly committed to being emotionally sensitive (p=0.055) and managing somatization (p=0.056), compared with the untrained residents. The trained residents also evidenced more knowledge of psychosocial medicine than did the untrained residents (p<0.001). CONCLUSIONS: Intensive psychosocial training improves residents’ self-confidence in their ability regarding key psychosocial behaviors and increases their knowledge of psychosocial medicine. Training also increases anticipation of positive outcomes from and personal commitment to some, but not all, psychosocial skills. Presented at the annual meeting of the Society of General Internal Medicine, Washington, DC, April 27–29, 1994. Supported by the Fetzer Institute in Kalamazoo, MI.     

Abnormal regulation of Mg2+ transport via Na/Mg exchanger in sickle erythrocytes

Erythrocyte magnesium (Mg2+) deficiency has been demonstrated in sickle cell disease to contribute to erythrocyte dehydration, K loss, and thus sickling. No studies have assessed the functional properties of the Na/Mg exchanger in sickle cell disease. Using Mg(2+)-loaded erythrocytes, we measured Mg2+ efflux induced by extracellular Na+. We estimated that the Na/Mg exchanger had higher maximal velocity, higher affinity for Na+, and lower cooperativity for Mg2+ in sickle than in normal erythrocytes. The activity of the exchanger was markedly decreased by hypotonic and hypertonic conditions in normal erythrocytes but not in sickle erythrocytes. Studies of density-separated erythrocytes showed that the activity of the exchanger decreased as the mean cellular hemoglobin concentration increased in normal but not in sickle erythrocytes. Inhibition of protein kinase C (PKC) activity by calphostin C and chelerythrine increased the activity of the exchanger in normal but not in sickle erythrocytes. Inhibition of serine/threonine phosphatases did not affect the activity of the exchanger in either normal or sickle erythrocytes. Altogether, these data indicate that the Na/Mg exchanger is abnormally regulated in sickle erythrocytes. Therefore, Mg2+ depletion in sickle erythrocytes might be mediated by an up-regulated Na/Mg exchanger, possibly by dephosphorylation of the transporter or a closely associated regulator.     

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

It has been shown that mice with complete deficiency of all 4.1R protein isoforms (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology (spherocytosis) and decreased membrane stability. Here, we characterized the Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice. Compared with wild-type, the Gardos channel of 4.1-/- erythrocytes showed an increase in Vmax (9.75 +/- 1.06 vs 6.08 +/- 0.09 mM cell x minute; P < .04) and a decrease in Km (1.01 +/- 0.06 vs 1.47 +/- 1.02 microM; P < .03), indicating an increased sensitivity to activation by intracellular calcium. In vivo function of the Gardos channel was assessed by the oral administration of clotrimazole, a well-characterized Gardos channel blocker. Clotrimazole treatment resulted in worsening of anemia and hemolysis, with decreased red cell survival and increased numbers of circulating hyperchromic spherocytes and microspherocytes. Clotrimazole induced similar changes in 4.2-/- and band 3+/- mice, indicating that these effects of the Gardos channel are shared in different models of murine spherocytosis. Thus, potassium and water loss through the Gardos channel may play an important protective role in compensating for the reduced surface-membrane area of hereditary spherocytosis (HS) erythrocytes and reducing hemolysis in erythrocytes with cytoskeletal impairments.     

Prognostic factors associated with postoperative complications in liver transplant]

OBJECTIVES: the postoperative evolution of patients submitted to orthotopic liver transplant (OLT) is frequently associated with the appearance of different types of complications such as renal failure, graft rejection, infections, and neurological disorders. These complications are the most significant causes of early morbidity and mortality in patients undergoing OLT. The purpose of the present study was the identification of factors related to the different postoperative complications after OLT. Experimental design: a prospective study was carried out. PATIENTS: seventy-eight variables were analyzed in 32 consecutive patients undergoing OLT. The factors independently associated with the appearance of postoperative complications were identified using a stepwise logistic regression analysis. RESULTS: the multivariate analysis showed that malondialdehyde and creatinine pretransplant serum levels were associated with the development of renal dysfunction. The pretransplant levels of haemoglobin and the units of platelets administered during surgery were prognostic factors of infections. Acute graft rejection was predicted by ?-glutamyl transpeptidase and total bilirubin serum levels. The pretransplant sodium and glutaredoxin levels in serum were associated with neurological complications. CONCLUSIONS: we propose these markers for the identification of high-risk patients allowing an early surveillance and/or treatment to improve morbidity and survival in patients submitted to OLT.