Evaluation of plasma agmatine level and its metabolic pathway in patients with bipolar disorder during manic episode and remission period.

Objectives: Agmatine is a cationic amine resulting from the decarboxylation of l-arginine. Agmatine has neuroprotective, anti-inflammatory, anti-stress, and anti-depressant properties. In this study, plasma agmatine, arginine decarboxylase, and agmatinase levels were measured during manic episode and remission period in patients with bipolar disorder. Methods: Thirty healthy volunteers and 30 patients who meet Bipolar Disorder Manic Episode diagnostic criteria were included in the study. Additionally, the changes in the patient group between manic episode and remission period were examined. We evaluated the relationship between levels of l-arginine and arginine decarboxylase in the agmatine synthesis pathway, and level of agmatinase that degrades agmatine. Results: Levels of agmatine and l-arginine were significantly increased than control group during manic episode (p < .01). All parameters were increased during manic episode compared to remission period (p < .05). Agmatinase was significantly decreased both during manic episode (p < .01) and remission period (p < .05) in comparison to the control group. Arginine decarboxylase levels did not show a significant difference between the groups (p > .05). Conclusions: This study indicate that there may be a relationship between bipolar disorder and agmatine and its metabolic pathway. Nonetheless, we believe more comprehensive studies are needed in order to reveal the role of agmatine in etiology of bipolar disorder. Key points Agmantine, agmatinase, l-arginine and arginine decarboxylase levels in BD have not been explored before. Various neuro-chemical mechanisms act to increase agmatine in BD; however, agmatine could have elevated to compensate agmatine deficit prior to the manifestation of the disease as in schizophrenia. Elevated agmatine degradation resulting from excess expression of agmatinase which is suggested to be effective in pathogenesis of mood disorders was compensated by this way. Elevated agmatine may be one of the causes which play a role in mania development. Elevated agmatine levels are also suggested to trigger psychosis and be related with the etiology of manic episode and lead to BD.

Donor-specific HLA antibodies in predicting crossmatch outcome: Comparison of three different laboratory techniques.

The virtual crossmatch, which is based on single antigen bead technology, is used in the prediction of crossmatch results. However, this assay differs in sensitivity and specificity from crossmatch methods. In our study, the results of physical crossmatches, performed with three different methods, were assessed against virtual crossmatch results. The aim was to determine the potential cut-off values for donor specific antibodies (DSA) that would predict the crossmatch results obtained by different methods. The results of different crossmatch techniques were correlated with the virtual crossmatch. The receiver operating characteristic (ROC) analysis revealed the Flow cytometric crossmatch (FCXM) and Luminex crossmatch (LXM) to be the most accurate, with area under curve (AUC) values of 0.861 and 0.805, respectively. While we found that the virtual crossmatch correlated well with all the crossmatch results, FCXM produced the best results (83% of the DSA detected). LXM outperformed the other tests in terms of the accuracy in separating class II DSA.

Genetic polymorphisms of heme-oxygenase 1 (HO-1) may impact on acute kidney injury, bronchopulmonary dysplasia, and mortality in premature infants.

BACKGROUND: Heme oxygenase 1 (HO1) catalyzes heme degradation, and offers protection for several organs, including the kidney. Genetic polymorphisms of HO-1 are associated with poor clinical outcomes in several populations. POPULATION: We prospectively enrolled 117 premature infants (birth weight ≤1,200 g or postgestational age ≤31 wk) and evaluated two DNA genetic variants proximal to the promoter region of HO-1 (GT(n) repeats, and -413T>A SNP). We evaluated how these polymorphisms affect two clinical outcomes: (i) Acute Kidney Injury (AKI)-rise in serum creatinine (SCr) ≥ 0.3 mg/dl or ≥ 150-200% from lowest previous value, (ii) the composite of mortality and bronchopulmonary dysplasia (BPD) defined as receipt of oxygen at 36 wk postmenstrual age. RESULTS: AKI occurred in 34/117 (29%) of neonates; 12/117 (10%) died; 29/105 (28%) survivors had BPD. Neonates with TT genotype at 413T>A before the HO-1 promoter had higher rates of AKI (P < 0.05). There was no difference in number of GT(n) repeats and clinical outcomes. CONCLUSION: We did not find an association between the GT(n) tandem repeat of HO-1 and AKI nor BPD/mortality. However, infants with TT genotype of the 413T>A genetic alteration had lower incidence of AKI. Further studies using larger cohorts are needed to better understand these relationships.

Clinical and molecular aspects of 30 patients with late-onset Pompe disease (LOPD): unusual features and response to treatment.

Pompe disease is a rare metabolic disorder, due to mutations in the gene encoding acid alpha-glucosidase (GAA), of which infantile and late-onset forms may occur. Aim of the work was to analyze clinical and laboratory data of a cohort of late-onset Pompe disease (LOPD) patients, collected during the last 15 years and to point out unusual phenotypic/genotypic features as well as enzyme replacement therapy (ERT) responses. We diagnosed 30 LOPD patients; at follow-up, they underwent motor, respiratory, cardiac and muscle MRI evaluations. Motor performances were tested by Walton Gardner-Medwin, GSGC and 6MWT tests. Respiratory function was assessed as FVC% in upright/supine position. LOPD presentations were represented by presymptomatic hyperCKemia (37%), proximal/axial muscle weakness (53%) and respiratory impairment (10%). Median diagnostic delay was 8.6 years (± 8.8). Atypical features were observed in 4 patients: marked distal muscle weakness and severe hearing loss at onset, as well as leukoencephalopathy and mesial temporal sclerosis during the disease course. By GAA sequence analysis, two causing mutations were detected in 22/30 patients, only one in the remaining 8 subjects. Overall, 29/30 patients harbored the common c.-32-13T>G mutation (2 were homozygous). Two new DNA variations were discovered (c.2395C>G, c.1771C>T). 14 patients received ERT for up to 60 months. Our study confirms LOPD clinical and genetic heterogeneity: atypical features may contribute to expand the clinical phenotype highlighting its multi-systemic nature. A timely diagnosis could allow early ERT start. An accurate follow-up is recommended to evaluate treatment responses.

Chronic kidney disease management program in Shahreza, Iran.

INTRODUCTION: Chronic kidney disease (CKD) is a public health problem that needs an integrated program to be detected, monitored, and controlled. This study reports the results of a CKD program designed and implemented in Shahreza, Iran. MATERIALS AND METHODS: After initial evaluation of CKD in Shahreza, a CKD management program was developed in the Ministry of Health and the pilot project was started in February 2011 in Shahreza rural areas. The patients at risk, including those with diabetes mellitus and hypertension, were tested with serum creatinine and urine albumin-creatinine ratio. The CKD management program included training, screening, monitoring, and controlling of weight, hypertension, diabetes mellitus, lipids, and vitamin D. RESULTS: This pilot program was organized in the rural population aged over 30 years who were suffering from hypertension, diabetes mellitus, or both, and resulted in the discovery of cases in various stages of CKD. The prevalence of CKD in this high-risk group was 21.5%. Persistent albuminuria and a glomerular filtration rate less than 60 mL/min/1.73 m(2) were 13% and 11%, respectively. The rate of CKD stages 1, 2, 3a, 3b, 4, and 5 were 2.75%, 6.82%, 10.08%, 0.92%, 0.31%, and 0.17% respectively. After 1 year of the program implemented, incidence rate of CKD was 24% and improvement rate was 21%. In diabetic patients, the mean of hemoglobin A1c decreased from 8.5 ± 1.9% to 7.5% ± 1.8%. CONCLUSIONS: Integration of CKD programs in primary health care is possible and results in improvement in management of CKD patients.

Metabolic profiling of plasma from sows before parturition and during lactation using a liquid chromatography-mass spectrometry-based approach.

During transition from late gestation to lactation, the sow undergoes large and sudden metabolic changes to adapt from anabolic to catabolic metabolism. Little is known about changes in nutrient uptake and intermediary metabolism of transition sows. This study was undertaken to screen the metabolic profile for qualitative changes in nutrient uptake and metabolism during transition. Four sows were fitted with permanent catheters in artery femoralis (AF), portal vein (PV), and hepatic vein (HV) (sampling sites). Sows were fed a standard lactation diet from 15 d prior to 28 d after parturition. Blood samples were taken 1.5 h after feeding on days -10, -3, 3, and 17 relative to parturition and plasma metabolites were analyzed by a liquid chromatography-mass spectrometry-based approach. Principal components analysis was performed to visualize the metabolic profiles and to screen for intermediary metabolites altered during the transition period. The metabolic profile of sows on day 3 after parturition was distinct from other days. Plasma betaine, Pro, and some unidentified lipid compounds contributed to the separation on day 3; betaine and Pro were lowered by 30% at day 3 compared to day -10 and day -3 (P < 0.001). Plasma choline, Pro, creatine, and unidentified lipid compounds contributed to the separation due to sampling sites. Plasma choline was lowest in HV, intermediate in AF, and highest in PV (P < 0.001) plasma, indicating net absorption from the gastrointestinal tract (PV vs. AF) and liver metabolism (HV vs. PV). The majority of unidentified metabolites found using the loadings plots that were affected by day or sampling site or both were revealed as lipid compounds, that is, bile acid, cholesterol, glycerol, phosphatidyl, sphingomyelin, or acylglycerol derivatives. In conclusion, the intermediary metabolism of sows, especially for fat, changed during transition, and a deeper understanding and detection of involved metabolites are needed to optimize sow feeding during transition.

First identification of the hepatotoxic microcystins in the serum of a chronically exposed human population together with indication of hepatocellular damage.

Hepatotoxic microcystins (MCs) are the most commonly reported cyanotoxins in eutrophic freshwaters. In 1996, human intoxications by MCs caused deaths of 76 patients at Caruaru dialysis centers in Brazil. So far, there have been no direct evidences of MC occurrence in human tissue in consequence of exposure to MC. In this study, we improved cleanup procedures for detecting MCs in serum sample using liquid chromatography-mass spectrometry, and confirmed for the first time the presence of MCs in serum samples (average 0.39 ng/ml, which amounts to ca. 1/87 of the concentrations found in tissue samples of the Caruaru victims) of fishermen at Lake Chaohu. Daily intake by the fishermen was estimated to be in the range of 2.2-3.9 microg MC-LReq, whereas the provisional World Health Organization tolerable daily intake (TDI) for daily lifetime exposure is 0.04 microg/kg or 2-3 microg per person. Moreover, statistical analysis showed closer positive relationships between MC serum concentrations and concentrations of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase than between the MC concentrations and other biochemical indicators. Thus, the data raise the question whether extended exposure in the range of the TDI or up to a factor of 10 above it may already lead to indication of liver damage. The results also demonstrate a risk of health effects from chronic exposure to MCs at least for populations with high levels of exposure, like these fishermen.

Clinical presentation and renal evaluation of human visceral leishmaniasis (kala-azar): a retrospective study of 57 patients in Brazil.

Visceral leishmaniasis is an endemic disease caused by various species of Leishmania. We made a retrospective study of 57 consecutive patients with visceral leishmaniasis in Brazil. Patients with visceral leishmaniasis were identified using the registries of the São José Infectious Diseases Hospital. The sample was divided into two groups: patients with serum creatinine (Scr) <1.3mg/dL and Scr > or = 1.3mg/dL. We compared these two groups for differences in clinical manifestations and laboratory features. Patients' mean age was 28 +/- 18 years old; 74% were male. The main clinical symptoms and signs presented in the initial evaluation were: fever (97%), splenomegaly (96.4%), weight loss (95.5%), pallor (93.6%), cough (89.7%), hepatomegaly (87.2%), asthenia (83.3%), anorexia (82.9%) and vomiting (73.9%). Acute renal failure was found in 15 patients (26.3%) and eight of these patients had ARF before amphotericin B administration. The mean age was higher in the group with Scr > or =1.3mg/dL. Death occurred in three cases; all deaths occurred with Scr > or =1.3mg/dL. There were no significant differences in the frequencies of the clinical symptoms and signs between the two groups. The laboratory data and demographic characteristics were significantly worse in the Scr > or =1.3mg/dL group. Renal dysfunction is an important feature of this disease; it is associated with important morbidity and can increase mortality.

Clinical presentation and renal evaluation of human visceral leishmaniasis (kala-azar): a retrospective study of 57 patients in Brazil

Visceral leishmaniasis is an endemic disease caused by various species of Leishmania. We made a retrospective study of 57 consecutive patients with visceral leishmaniasis in Brazil. Patients with visceral leishmaniasis were identified using the registries of the São José Infectious Diseases Hospital. The sample was divided into two groups: patients with serum creatinine (Scr) <1.3mg/dL and Scr > 1.3mg/dL. We compared these two groups for differences in clinical manifestations and laboratory features. Patients' mean age was 28 ± 18 years old; 74 percent were male. The main clinical symptoms and signs presented in the initial evaluation were: fever (97 percent), splenomegaly (96.4 percent), weight loss (95.5 percent), pallor (93.6 percent), cough (89.7 percent), hepatomegaly (87.2 percent), asthenia (83.3 percent), anorexia (82.9 percent) and vomiting (73.9 percent). Acute renal failure was found in 15 patients (26.3 percent) and eight of these patients had ARF before amphotericin B administration. The mean age was higher in the group with Scr > 1.3mg/dL. Death occurred in three cases; all deaths occurred with Scr > 1.3mg/dL. There were no significant differences in the frequencies of the clinical symptoms and signs between the two groups. The laboratory data and demographic characteristics were significantly worse in the Scr > 1.3mg/dL group. Renal dysfunction is an important feature of this disease; it is associated with important morbidity and can increase mortality.

Polyoma virus nephropathy, first reported case in Saudi Arabia.

Polyoma virus nephropathy (BK virus) is being recognized as an important cause of graft failure. It is usually confused with acute rejection. No cases have been reported from the kingdom of Saudi Arabia. We report a case of a Saudi gentleman, who was transplanted outside the country, with persistently elevated creatinine and urethral stenosis. He was treated for acute rejection on more than one occasion with no significant improvement in his renal function. Polyoma virus nephropathy was diagnosed by detecting the virus DNA by the Poly chain reaction technique (PCR). The patient's renal function stabilized after the calcineurin inhibitors were discontinued.

Regression of cardiac enzyme and ventriculocoronary communication in an infant with pulmonary atresia and intact ventricular septum after radiofrequency valvulotomy and valvuloplasty.

I report on a 3-month-old infant with pulmonary atresia-intact ventricular septum and ventriculocoronary communication (VCC) who underwent percutaneous radiofrequency valvulotomy and valvuloplasty (RFVV). The patient's cardiac troponin-I, creatine kinase (CK), and myocardial fraction of (CK-MB) were elevated before RFVV and were gradually regressed to normal levels 12 days after RFVV. The VCC disappeared after RFVV. The transvalvular pressure gradients across the pulmonary valve were less than 30 mmHg in the follow-up echocardiography at 4-12 months of age. Oxygen saturation was approximately 90% in room air. Dipyridamole-thallium myocardial scintigraphy showed positive reperfusion over the apex and interventricular septum.

Serum biochemical values in sled dogs before and after competing in long-distance races.

OBJECTIVE: To measure and compare blood values in sled dogs before and after long-distance racing. DESIGN: Prospective study. ANIMALS: 17 adult sled dogs in the 1991 Iditarod Trail Sled Dog Race and 21 in a simulated sled dog race. PROCEDURE: Blood samples were obtained from 17 dogs 7 days before they began and after they finished (finisher group) or were eliminated from (nonfinisher group) the Iditarod Trail Sled Dog Race. Blood samples were also obtained from 21 dogs before and after a simulated sled dog race. RESULTS: In finisher-group dogs, BUN and uric acid (UA) concentrations were increased after racing; nonfinisher-group dogs had significantly lower postrace BUN and UA concentrations. Significant increases in creatine kinase (CK) and aspartate transferase (AST) activities were detected in all dogs after racing, and postrace values were higher in nonfinisher-group dogs, compared with finisher-group dogs. Mean alkaline phosphate activities were significantly increased after racing in nonfinisher-group dogs only. In dogs that ran the simulated race, postrace values for serum albumin, total protein, calcium, and potassium concentrations, as well as Hct, hemoglobin concentration, and RBC count, were significantly lower than prerace values. Postrace values for alkaline phosphate, alanine transaminase, AST, lactate dehydrogenase, CK, BUN, and UA were significantly higher than prerace values. CLINICAL IMPLICATIONS: High CK activities are indicative of severe muscle degeneration and, in sled dogs, may represent a degree of muscle breakdown beyond which a dog cannot continue to work. Markedly high CK, and possibly AST, serum activities may be indicators of performance failure in sled dogs competing in long-distance races.