Medical complications of anorexia nervosa.

Anorexia nervosa is a mental illness characterized by self-starvation, marked weight loss, and malnutrition. As the illness worsens, numerous medical complications develop throughout the body. Some of these resolve with effective nutritional rehabilitation and weight gain, whereas others can lead to permanent damage.

Melatonin improves hyperglycemia induced damages in rat brain.

BACKGROUND: Diabetes mellitus is an endocrine disorder which is characterized by the development of resistance to the cellular activity of insulin or inadequate insulin production. It leads to hyperglycemia, prolonged inflammation, and oxidative stress. Oxidative stress is assumed to play an important role in the development of diabetic complications. Melatonin is the hormone that interacts with insulin in diabetes. Therefore, in this study, the effects of melatonin treatment with or without insulin were examined in diabetic rat brain. METHODS: Rats were divided into five groups as control, diabetes, diabetes + insulin, diabetes + melatonin, and diabetes + melatonin + insulin. Experimental diabetes was induced by streptozotocin (60 mg/kg, i.p.). Twelve weeks after diabetes induction, rats were decapitated. Malondialdehyde, glutathione, sialic acid and nitric oxide levels, superoxide dismutase, catalase, glutathione-S-transferase, myeloperoxidase, and tissue factor activities were determined in brain tissue. RESULTS: Melatonin alone showed its antioxidant effect by increasing brain glutathione level, superoxide dismutase, catalase, and glutathione-S-transferase activities and decreasing malondialdehyde level in experimental diabetes. Although insulin did not have a significant effect on glutathione and glutathione-S-transferase, its effects on lipid peroxidation, superoxide dismutase, and catalase were similar to melatonin; insulin also decreased myolopeoxidase activity and increased tissue factor activity. Combined melatonin and insulin treatment mimicked the effects of insulin. CONCLUSION: Addition of melatonin to the insulin treatment did not change the effects of insulin, but the detailed role of melatonin alone in the treatment of diabetes merits further experimental and clinical investigation.

Protective effect of hydroxytyrosol in arsenic-induced mitochondrial dysfunction in rat brain.

The present study was planned to investigate the protective effect of hydroxytyrosol (HT) against arsenic (As)-induced mitochondrial dysfunction in rat brain. Rats exposed to sodium arsenite (25 ppm for 8 weeks) showed decreased mitochondrial complexes (I, II, IV) activities, mitochondrial superoxide dismutase (MnSOD), and catalase activities in brain mitochondria. As-treated rats showed reduced mRNA expression of complex I (ND-1, ND-2), IV (COX-1, COX-4) subunits, and uncoupling protein-2 (UCP-2). In addition to this, As exposure downregulated the protein expression of MnSOD. Administration of HT with As restored the enzymatic activities of mitochondrial complexes, MnSOD and catalase, increased the mRNA levels of complexes subunits and UCP-2 as well as proteins level of MnSOD. These results suggest that HT efficiently restores mitochondrial dysfunction in As neurotoxicity and might be used as potential mitoprotective agent in future.

The Protective Effect of Radix Polygoni Multiflori on Diabetic Encephalopathy via Regulating Myosin Light Chain Kinase Expression.

Currently there has been no effective treatment of diabetic encephalopathy. Radix Polygoni Multiflori, a famous traditional Chinese medicine, is widely used in antiaging treatment, especially in prevention and treatment of Alzheimer's diseases. In this study we tried to explore the effect of Radix Polygoni Multiflori on cognitive function among diabetic rats with demonstrated cognitive impairment. SD rats were divided into group A (control group), group B (diabetes), group C (treated with Radix Polygoni Multiflori at the dose of 2 g/kg/d), and group D (treated with same drug at the dose of 1 g/kg/d). The results showed that 8 weeks of Radix Polygoni Multiflori treatment could improve the cognitive dysfunction of diabetic rats (P < 0.01), recover the ultrastructure of hippocampal neurons, and increase the number of synapses in a dose-dependent manner. Further experiment also suggested that the neuroprotective effect of Radix Polygoni Multiflori was partly achieved by downregulating MLCK expression in hippocampus via ERK signaling.

Therapeutic intravascular normothermia reduces the burden of metabolic crisis.

BACKGROUND: We aim to investigate whether therapeutic-induced normothermia (TIN) ≤ 37.5 °C, by means of intravascular cooling devices is more efficacious than standard medical therapy (MED) in alleviating metabolic crisis (MC) acutely following traumatic brain injury (TBI). METHODS: We retrospectively analyzed data from 62 patients with severe TBI, GCS ≤ 8. We divided the cohort into two groups. (1) Patients who had temperature controlled via standard medical therapies (n = 52), (2) TIN group (n = 10). For each group, we analyzed the percent time spent in normothermia, and in MC. Furthermore, we focused the investigation on pre-TIN versus post-TIN comparing temp, intracranial pressure (ICP), sedation, and MC before and after intravascular cooling. RESULTS: TIN patients had a better temperature control than MED group (60.72 ± 19.53 vs 69.75 ± 24.98 %, p < 0.001) and spent shorter time in MC (22.60 ± 20.45 vs 32.17 ± 27.25 %, p < 0.001). Temperature control was associated with reduced incidence of MC in TIN (OR 0.51, CI 0.38-0.67, p < 0.001, p < 0.001) but not in MED (OR 0.97, CI 0.87-1.1, p = 0.63). Within TIN group analysis, following TIN both temperature and incidence of MC improved from 37.62 ± 0.34 versus 36.69 ± 0.90 °C (p < 0.005) and 41.95 ± 27.74 % before to 8.35 ± 9.78 % (p = 0.005) after, respectively. ICP was well controlled both before and after intravascular cooling (13.07 vs 15.83 mmHg, p = 0.20). CONCLUSION: Therapeutic normothermia, using intravascular cooling, results in a reduction in the burden of MC. This differential effect occurs despite equivalent control of ICP in both TIN and MED treatments. These results demonstrate proof of concept of normothermia, when applied in a controlled manner, being neuroprotective.

[Delirium in the clinical practice of a therapist].

Delirium is a neuropsychiatric condition that may complicate any visceral disease. Its rate is especially high among patients with inflammatory diseases or metabolic disturbances and in the elderly. Brain injury concurrent with an abnormal stress response underlies the development of delirium. The clinical picture of delirium is characterized by clouding of consciousness accompanied by global cognitive and behavioral changes. According to the nature of changes in motor behavior, delirium is divided into hyperactive, hypoactive, and mixed subtypes. Special scales, such as Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), are used to identify delirium. Management of delirium includes specific therapy for the underlying disease and adequate care. Low-dose neuroleptics, haloperidol in particular, are recommended to correct behavioral changes.

Epidermal growth factor receptor transactivation is necessary for glucagon-like peptide-1 to protect PC12 cells from apoptosis.

AIM: Patients with long-standing diabetes commonly develop diabetic encephalopathy, which is characterized by cognitive impairment and dementia. To identify potential treatments for diabetic encephalopathy, we focused on the protective action of glucagon-like peptide-1 (GLP-1) against neural cell apoptosis. In this study, we evaluated whether exposure of cells to GLP-1 leads to epidermal growth factor receptor (EGFR) transactivation and signaling through the PI3K/Akt/mTOR/GCLc/redox pathway, which we previously reported. METHODS: We monitored the phosphorylation of EGFR and Akt in PC12 cells exposed to MG and GLP-1 that had been first incubated in the presence or absence of various inhibitors of EGFR transactivation. RESULTS: DAPI staining revealed that pretreatment of cells with BiPS, HB-EGF and anti-TGF-α neutralization antibodies or AG1478 abrogated the ability of GLP-1 to rescue cells from MG-induced apoptosis. We show that exposure of PC12 cells to GLP-1 induces EGFR phosphorylation and that this effect was inhibited by prior exposure of the cells to BiPS, HB-EGF and anti-TGF-α neutralization antibodies or AG1478. Interestingly, these agents also diminished the capacity of GLP-1 to protect cells from MG-induced apoptosis. Moreover, these agents reduced GLP-1-induced phosphorylation of Akt. EGF itself also protected the cells from MG-induced apoptosis and induced phosphorylation of Akt, which was inhibited by LY294002. CONCLUSION: The neuroprotective effects of GLP-1 against MG-induced apoptosis are mediated by EGFR transactivation, which signals through the PI3K/Akt/mTOR/GCLc/redox pathway in PC12 cells.

Neuroprotective properties of aucubin in diabetic rats and diabetic encephalopathy rats.

In this study, we determined the neuroprotective effect of aucubin on diabetes and diabetic encephalopathy. With the exception of the control group, all rats received intraperitoneal injections of streptozotocin (STZ; 60 mg/kg) to induce type 1 diabetes mellitus (DM). Aucubin (1, 5, 10 mg/kg ip) was used after induction of DM (immediately) and diabetic encephalopathy (65 days after the induction of diabetes). The diabetic encephalopathy treatment groups were divided into short-term and long-term treatment groups. Treatment responses to all parameters were examined (body weight, plasma glucose, Y-maze error rates and proportion of apoptotic cells). In diabetic rats, aucubin controlled blood glucose levels effectively, prevented complications, and improved the quality of life of diabetic rats. In diabetic encephalopathy, aucubin significantly rescued neurons in the hippocampal CA1 subfield and reduced working errors during behavioral testing. The significant neuroprotective effect of aucubin could be seen not only in the short term (15 days) but also in the long term (45 days), which was a highly encouraging finding. These data suggest that aucubin may be a potential neuroprotective agent.

Pathology supported genetic testing and treatment of cardiovascular disease in middle age for prevention of Alzheimer's disease.

Chronic, multi-factorial conditions caused by a complex interaction between genetic and environmental risk factors frequently share common disease mechanisms, as evidenced by an overlap between genetic risk factors for cardiovascular disease (CVD) and Alzheimer's disease (AD). Single nucleotide polymorphisms (SNPs) in several genes including ApoE, MTHFR, HFE and FTO are known to increase the risk of both conditions. The E4 allele of the ApoE polymorphism is the most extensively studied risk factor for AD and increases the risk of coronary heart disease by approximately 40%. It furthermore displays differential therapeutic responses with use of cholesterol-lowering statins and acetylcholinesterase inhibitors, which may also be due to variation in the CYP2D6 gene in some patients. Disease expression may be triggered by gene-environment interaction causing conversion of minor metabolic abnormalities into major brain disease due to cumulative risk. A growing body of evidence supports the assessment and treatment of CVD risk factors in midlife as a preventable cause of cognitive decline, morbidity and mortality in old age. In this review, the concept of pathology supported genetic testing (PSGT) for CVD is described in this context. PSGT combines DNA testing with biochemical measurements to determine gene expression and to monitor response to treatment. The aim is to diagnose treatable disease subtypes of complex disorders, facilitate prevention of cumulative risk and formulate intervention strategies guided from the genetic background. CVD provides a model to address the lifestyle link in most chronic diseases with a genetic component. Similar preventative measures would apply for optimisation of heart and brain health.

The development of a global program for the elimination of brain damage due to iodine deficiency.

Iodine deficiency is the most common preventable cause of brain damage with more than 2 billion people from 130 countries at risk. The global problem of iodine deficiency has been redefined by a readily transmitted population concept, with an easy acronym - the concept of the iodine deficiency disorders (IDD) - referring to all the effects of iodine deficiency in a population, that can be totally prevented by correction of iodine deficiency with special emphasis on brain damage and not just to goitre and cretinism (1983). This was followed by the creation of the International Council for Control of Iodine Deficiency Disorders (ICCIDD) supported by WHO and UNICEF with 700 multidisciplinary professionals from more than 100 countries, committed to providing technical assistance to national programs for the elimination of IDD (1986). The WHO policy of Universal Salt Iodization (USI) has been widely adopted which requires iodization of all food for human and animal consumption by the use of iodized salt (25-40 mg I/kilo). Simple practical methods for monitoring - by the measurement of salt iodine and urine iodine were developed and promoted on a large scale with the technical assistance of the ICCIDD.

Avoid adding insult to injury - correct management of sick female endurance athletes.

OBJECTIVES: To evaluate the efficacy of Ringer's lactate, isotonic saline and hypertonic saline on the clinical and biochemical recovery of athletes with exercise-associated hyponatraemic encephalopathy caused by fluid overload. METHODS: We retrospectively reviewed serial blood sodium concentrations (Na+) and qualitative signs of recovery and time to recovery in two healthy menstruant females hospitalised with dilutional exercise-associated hyponatraemic encephalopathy after withdrawal from the 2011 Comrades Marathon (89 km) and Argus Cycle Tour (109 km). RESULTS: Improvements in blood Na+ did not occur with intravenous administration of Ringer's lactate solution, but did occur with administration of isotonic and hypertonic saline. Qualitative improvements in mental status were not quantitatively related to the biochemical value of blood Na+ or subsequent return to normonatraemia. CONCLUSIONS; Hyponatraemia should be suspected in all female athletes presenting to the medical area of endurance races with vomiting, altered mental status and a history of high fluid intake. If a diagnosis of exercise-associated hyponatraemia with cerebral encephalopathy is confirmed, the treatment of choice is administration of an intravenous bolus of hypertonic saline. Administration of Ringer's lactate should be discouraged, as this does not correct Na+ and appears to delay recovery.

[Bio-ecological control of chronic liver disease and encephalopathy]. / Controllo bio-ecologico della cirrosi epatica e dell'encefalopatia.

Minimal encephalopathy was originally associated with chronic liver disease but is increasingly associated with most other chronic diseases and particularly with diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and with obesity. It is increasingly with dramatically increased and more or less permanent increase in systemic inflammation, most likely a result of Western lifestyle. Frequent physical exercise and intake of foods rich in vitamins, antioxidants, fibres, lactic acid bacteria etc in combination with reduction in intake of refined and processed foods is known to reduce systemic inflammation and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei, lb plantarum and pediococcus pentosaceus have proven effective to reduce inflammation and eliminate encephalopathy. Significant reduction in blood ammonia levels and endotoxin levels were reported in parallel to improvement of liver disease. Subsequent studies with other lactic acid bacteria seem to demonstrate suppression of inflammation and one study also provides evidence of clinical improvement.

New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children.

Hyponatremia is the most common electrolyte abnormality encountered in children. In the past decade, new advances have been made in understanding the pathogenesis of hyponatremic encephalopathy and in its prevention and treatment. Recent data have determined that hyponatremia is a more serious condition than previously believed. It is a major comorbidity factor for a variety of illnesses, and subtle neurological findings are common. It has now become apparent that the majority of hospital-acquired hyponatremia in children is iatrogenic and due in large part to the administration of hypotonic fluids to patients with elevated arginine vasopressin levels. Recent prospective studies have demonstrated that administration of 0.9% sodium chloride in maintenance fluids can prevent the development of hyponatremia. Risk factors, such as hypoxia and central nervous system (CNS) involvement, have been identified for the development of hyponatremic encephalopathy, which can lead to neurologic injury at mildly hyponatremic values. It has also become apparent that both children and adult patients are dying from symptomatic hyponatremia due to inadequate therapy. We have proposed the use of intermittent intravenous bolus therapy with 3% sodium chloride, 2 cc/kg with a maximum of 100 cc, to rapidly reverse CNS symptoms and at the same time avoid the possibility of overcorrection of hyponatremia. In this review, we discuss how to recognize patients at risk for inadvertent overcorrection of hyponatremia and what measures should taken to prevent this, including the judicious use of 1-desamino-8d-arginine vasopressin (dDAVP).

Defectos de creatina cerebral: ¿cómo poder diagnosticar estas enfermedades y cambiar su evolución? / Brain creatine defects: how can these uncommon diseases be diagnosed and their evolution changed?

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Low incidence of neurologic events during long-term support with the HeartMate XVE left ventricular assist device.

Neurologic events during left ventricular assist device (LVAD) support are associated with significant morbidity and death. To evaluate this problem, we analyzed neurocognitive function and the frequency and incidence of neurologic events in 21 consecutive patients who were undergoing long-term support with the HeartMate XVE LVAD (Thoratec Corporation; Pleasanton, Calif). The mean duration of LVAD support was 531 days (range, 55-1, 309 d); the cumulative support time was 11,188 days (30.7 yr). No patients received anticoagulant therapy, and most received aspirin. None experienced strokes or transient ischemic attacks. Twenty patients were discharged from the hospital; 2 were later readmitted because of transient changes in neurologic status (metabolic encephalopathy) that ultimately resolved. Neurologic function, as measured by the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Score (MRS), was abnormal before LVAD implantation but normal 6 and 12 months after (mean NIHSS, 23.6 before vs 0 after; mean MRS, 0.68 before vs 0.18 after). Neurocognitive function, as evaluated by the Boston Naming Test, Trail Making Test part B, and Block Design Test, also improved during LVAD support. Together, these findings indicate that few neurologic events occur during long-term HeartMate XVE LVAD support in the absence of anticoagulation therapy. They also suggest that modifications made to the HeartMate LVAD since the REMATCH trial have resulted in fewer complications, and that better patient selection and supportive care have improved outcomes.

Long-term non-surgical therapy of severe persistent congenital hyperinsulinism with glucagon.

BACKGROUND: Congenital hyperinsulinism (CHI) is characterized by severe hypoglycemia caused by dysregulated insulin secretion. The long-term outcome is dependent on prevention of hypoglycemic episodes to avoid the high risk of permanent brain damage. Severe cases are usually resistant to diazoxide or nifedipine. In addition, somatostatin analogues are ineffective in a subgroup of patients to achieve stable euglycemia. In these infants the only remaining long-term option has been subtotal pancreatectomy with high risk of diabetes mellitus. Intravenous infusions of glucagon are used as immediate treatment to stabilize euglycemia in affected newborns. The rationale of this treatment comes from the observation of an increased glycogen content of the liver when glycogenolysis is inhibited by insulin. OBJECTIVE: To review the efficacy and safety of long-term subcutaneous glucagon infusion as a potential therapeutic option for blood glucose stabilization in infants with severe CHI without the need of additional intravenous glucose or immediate surgical intervention. METHOD: Retrospective review of 9 children with CHI who received continuous subcutaneous infusion of glucagon for weeks or months. Glucagon was added to octreotide to replace octreotide-induced suppression of endogenous glucagon secretion, thereby liberating glucose by stimulation of hepatic glycogenolysis. In 3 cases, a stabilized formulation of glucagon was used to prevent glucagon crystallization that frequently occurs in smaller volumes. RESULTS: Introduction of glucagon allowed the reduction or discontinuation of central glucose infusion in all children studied. In 2 patients, glucagon was introduced due to recurrent hypoglycemia despite subtotal pancreatectomy. Six out of 9 children were discharged home on this treatment, which their parents were able to continue without further symptomatic hypoglycemia, convulsions or unconsciousness. In 3 children, subcutaneous glucagon was continuously administered for 1-4 years leading to stable euglycemia. However, 2 children with diffuse type still required subtotal pancreatectomy. As a possible side effect, 2 children developed erythema necrolyticum, which resolved after discontinuation of the glucagon infusion. This has been described before in glucagonoma. CONCLUSION: In this retrospective series, combination therapy of low-dose octreotide and subcutaneous glucagon infusion has been effective in preventing hypoglycemic episodes in severe CHI. We propose this may serve as a therapeutic option in place of high rates of glucose infusion through a central venous catheter and as an alternative to subtotal pancreatectomy in diffuse type of CHI.

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children.

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.

Aprotinin to improve cerebral outcome after hypothermic circulatory arrest: a study in a surviving porcine model.

BACKGROUND: Aprotinin is a serine protease inhibitor, which is usually used during cardiac surgery to reduce blood loss. There is evidence that aprotinin has neuroprotective effects during ischemia. We planned this study to evaluate its potential neuroprotective efficacy during hypothermic circulatory arrest (HCA). METHODS: Twenty piglets with a median weight of 25.7 kg (interquartile range, 23.9-26.6) were randomly assigned to receive aprotinin or placebo prior to a 75-minute period of HCA at 18 degrees C. Brain microdialysis parameters and neurological and histological scores were the primary outcome measures. RESULTS: Changes in brain metabolic parameters and histopathological findings were favorable in the aprotinin group. Brain lactate concentrations were significantly lower in the aprotinin group during the experiment (P = .02) along with blood lactate concentrations in the aprotinin group (P = .023). Brain glucose was significantly higher during the experiment (P = 0.02). Intracranial pressure tended to be higher in the control group. Two of 10 animals in the aprotinin group and 4 of 10 in the control group failed to reach full recovery on the seventh postoperative day. Four animals of 10 in the aprotinin group and 6 animals of 10 in the control group had brain infarction (P = .40). CONCLUSIONS: The present data suggest that aprotinin mitigates cerebral damage and improves neurological outcome following a period of HCA.