Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on the mouse testis.

Organophosphates like O,O-diethyl O-2-isopropyl-6-methyl pyrimidinyl-4-g-1-phosphorothioate (diazinon) are pesticides used worldwide, which can affect both animals and man even after a single exposure. Whereas their toxicity is due to acetylcholinesterase inhibition, their secondary toxic effects have been related to free oxygen radicals. This study evaluates the effects of a single dose of diazinon and melatonin-a powerful antioxidant-on plasmatic acetylcholinesterase activity and testis histopathology in adult mice 1 and 32 days post-treatment. Diazinon diminished the plasma acetylcholinesterase activity on day 1 post-treatment, although testosterone levels remained unaffected. Morphometrical analysis showed a decrease in seminiferous epithelium height (days 1 and 32), whereas an increase in testicular superoxide dismutase (SOD) activity was detected (day 32). Melatonin pretreatment prevented every alteration induced by diazinon, except the diminution of acetylcholinesterase plasmatic activity. Testicular damage might be due to elevated concentrations of free oxygen radicals released upon diazinon exposure, inducing alterations in the DNA and promoting local apoptosis; however, antioxidant pretreatment with melatonin prevents or diminishes this damage.

Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on mouse sperm DNA.

Toxic effects of pesticides are commonly associated with DNA damage. To evaluate the effect of the organophosphate diazinon on sperm DNA and to test whether melatonin could prevent this damage, male mice were intraperitoneally treated with melatonin, diazinon (1/3 or 2/3 LD50) or both; cauda epididymal spermatozoa were obtained on days 1 and 32 postinjection and tested for DNA alterations. On day 1, sperm from diazinon-treated mice showed augmented DNA breakages and reduced chromatin packaging, whilst DNA damage increased only in the diazinon 2/3 LD50 group. Micronucleus test of bone marrow cells demonstrated somatic cell chromosomal damage in both diazinon-treated groups. Pretreatment with melatonin before diazinon acute administration improved all parameters studied on day 1 pi. The organophosphorous pesticide diazinon is a dose-dependent testicular toxicant that alters the sperm DNA structure; melatonin is able to prevent this damage.

Requestioning depression in patients with cancer: contribution of somatic and affective symptoms to Beck's Depression Inventory.

BACKGROUND: Depressive symptoms are a major complaint reported by cancer patients. Somatic and affective symptoms can contribute to depression. PATIENTS AND METHODS: We investigated the prevalence of somatic and affective depressive symptoms with the Beck Depression Inventory (BDI) in 213 hospitalized cancer patients prior to the start of chemotherapy. RESULTS: Seventeen of 213 patients (8%) were screened positive for major depression; 40 (19%) had mild to moderate depressive symptoms. The corresponding figures for somatic and affective symptoms were 33.3% and 2.8% in the patients with major depression and 23.0% and 8.0% in those with mild to moderate depressive symptoms. Female patients, patients with solid tumour and those with functional limitations had significantly higher mean scores. All differences were related to higher scores in somatic and not in affective items. CONCLUSIONS: Most alterations in the BDI in cancer patients are related to somatic and not to affective symptoms and may be attributed not to depression but to severity of the underlying disease.

Reboxetine and cytochrome P450--comparison with paroxetine treatment in humans.

OBJECTIVES: The noradrenaline-selective antidepressant reboxetine in vitro is a weak inhibitor of both cytochrome P450 (CYP) 2D6 and CYP3A4. Thus, in this study the pharmacokinetics of reboxetine in relation to pharmacogenetics and the effects of reboxetine compared to paroxetine treatment on the CYP2D6 and CYP3A4 phenotype were analyzed in healthy control subjects. METHODS: Healthy male volunteers were treated with either 6 mg reboxetine (n = 26) or 30 mg paroxetine (n = 25). On Days 10/11 of treatment, serum concentrations of the antidepressants were measured and pharmacokinetic parameters calculated. Volunteers were phenotyped at the end of treatment and after at least 3 weeks washout (true phenotype) using 30 mg dextromethorphan (DM) hydrobromide given orally and measuring DM and metabolites in serum 2 h after intake. CYP2D6 and CYP2C19 genotypes were determined in parallel. RESULTS AND CONCLUSION: Reboxetine serum concentrations showed no correlation with the CYP2D6 genotype and the CYP2D6 phenotype, whereas paroxetine concentrations showed some dependence on CYP2D6. In contrast to in vitro investigations, indicating a major role of CYP3A4 in reboxetine metabolism, reboxetine concentrations in serum showed no correlation with the respective DM metabolic ratios. There was also no correlation between paroxetine concentrations and the CYP3A4 phenotype data. The CYP2C19 genotype (only heterozygosity) had no influence on reboxetine and paroxetine pharmacokinetics. There were only minor changes in the DM metabolite pattern on treatment with reboxetine and no evidence of enzyme inhibition was obtained. In contrast and as expected, paroxetine strongly inhibited CYP2D6. Thus, reboxetine treatment has no effect on the CYP2D6 genotype and no clinically relevant drug interactions involving CYP2D6 are anticipated.

Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31)P chemical shift spectroscopic-imaging study.

BACKGROUND: (31)Phosphorous magnetic resonance spectroscopy has been widely used to evaluate schizophrenic patients in comparison to control subjects, because it allows the investigation of both phospholipid and energy metabolism in vivo; however, the results achieved so far are inconsistent. Chemical shift imaging (CSI) has the advantage that instead of only one or a few preselected voxels the tissue of a whole brain slice can be examined. The aim of the present investigation was to determine whether the results of previous studies of our group, showing that phosphodiesters (PDE) are decreased in the frontal lobe of schizophrenic patients as compared to control subjects, might be confirmed in an independent unmedicated patient sample using the CSI technique. METHODS: A carefully selected new cohort including 11 neuroleptic-free schizophrenic patients and 11 age- and gender-matched healthy control subjects was recruited. CSI was applied and an innovative analysis method for CSI data based on a general linear model was used. RESULTS: PDE, phosphocreatine, and adenosine triphosphate (ATP) were found to be significantly decreased in the frontal lobe of patients with schizophrenia. CONCLUSIONS: Because PDE was decreased in schizophrenic patients, the membrane phospholipid hypothesis of schizophrenia could not be corroborated. Further results indicate decreased ATP production in the frontal lobe of patients with schizophrenia.

Increase of phosphodiesters during neuroleptic treatment of schizophrenics: a longitudinal 31P-magnetic resonance spectroscopic study.

BACKGROUND: Increased levels of phosphodiesters (PDE%) and reduced relative concentrations of phosphomonoesters (PME%) have been reported in unmedicated schizophrenics, whereas findings in brain of medicated patients were not consistent. METHODS: We determined in vivo the metabolism of phospholipids and high-energy phosphates in the left and right frontal lobes of 8 patients with schizophrenia using 31P-magnetic resonance spectroscopy (31P-MRS). Serial investigations were performed first after a neuroleptic-free period (mean 7.5 +/- 1.9 days) and second, after neuroleptic treatment (mean 20.6 +/- 11.1 days). RESULTS: PDE% increased significantly in the left frontal lobe (32.0 +/- 5.9% versus 36.9 +/- 5.6%, p = .009) after medication. All other parameters showed no significant differences. CONCLUSIONS: Our study suggests that neuroleptics do not decrease phospholipase A2 activity in schizophrenia. Individual neuroleptics may have different effects on phospholipase A2 activity as indicated by animal studies. An influence of neuroleptics on high-energy phosphates cannot be confirmed by our data.

A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients.

To assess mitochondrial function and test the hypothesis of an underlying oxidative phosphorylation defect in Alzheimer disease (AD), we evaluated the activities of mitochondrial respiratory chain enzyme complexes I+III, complexes II+III, complex IV (cytochrome c oxidase, COX), succinate dehydrogenase, and citrate synthase in the frontal cortex, temporal cortex, hippocampus, and cerebellum of 23 AD patients and 13 normal human brains. The major finding was a significant decrease in COX activity in AD temporal cortex and hippocampus, both whether activities were expressed per noncollagen protein content (49 +/-4.6 versus 78+/-10.8 nmol/min/mg NCP, P = 0.006; 23+/-1.9 versus 48.6+/-8.1 nmol/min/mg NCP, p = 0.003) or corrected for citrate synthase activity (1.6+/-0.2 versus 3+/-0.4, P = 0.001; 0.76+/-0.1 versus 1.76+/-0.26, P = 0.0009). There were no significant differences in the activities of complexes I+III, II+III, and of succinate dehydrogenase in any of the brain regions examined. Our results suggest a specific defect of COX in the AD brain versus the normal human brain, which may contribute to impaired energy generation. Biochemically, the defect is confined to selected brain regions, suggesting anatomic specificity.

Recurrent orbital myositis: report of a familial incidence.

BACKGROUND: In orbital myositis, painful diplopia develops owing to an enlargement of the extraocular muscles. Diagnosis is established based on history, clinical manifestations, and therapeutic response to steroids, with the findings of magnetic resonance imaging providing additional information. OBSERVATION: We observed a family in which 4 members had an ophthalmopathy suggestive of orbital myositis. The affected members are a sibling pair (female and male) and 2 children of the brothers of their father's father. CONCLUSION: The familial incidence suggests a potential genetic predisposition in the development of orbital myositis.

Myocardial respiratory chain enzyme activities in idiopathic dilated cardiomyopathy, and comparison with those in atherosclerotic coronary artery disease and valvular aortic stenosis.

Mitochondrial respiratory chain enzyme activities were measured in biopsies of left ventricular myocardium from 25 adults in 3 groups: cardiac transplant recipients with atherosclerotic coronary artery disease (CAD), transplant recipients with idiopathic dilated cardiomyopathy (IDC), and patients with compensatory left ventricular hypertrophy due to aortic valve stenosis (AS). Specific activities of complexes I + III and II + III were 21 +/- 12 and 58 +/- 21 nmol/min/mg of noncollagen protein, respectively, in CAD, and 56 +/- 21 and 96 +/- 57 nmol/min/mg, respectively, in IDC (p < 0.004 and < 0.03, respectively). Specimens from patients with AS had enzyme activities that were intermediate between those from patients with CAD and IDC. Myocardium of patients with transvalvular pressure gradients between 50 and 79 mm Hg showed low activities of complexes I + III and II + III (17 +/- 5 and 62 +/- 17 nmol/min/mg of noncollagen protein, respectively), whereas those with higher pressure gradients between 80 and 100 mm Hg had enzyme activities of complexes I + III and II + III equal to those in IDC (37 +/- 11 and 73 +/- 18 nmol/min/mg, respectively). The same results were obtained when enzyme activities were normalized for the activity of the mitochondrial matrix enzyme citrate synthase. The data suggest that a compensatory metabolic adaptation of the mitochondrial respiratory chain enzymes occurs in both AS and IDC. A reduction in enzyme activities that is observed in heart failure due to CAD and that may explain the contractile dysfunction in these patients cannot be confirmed in IDC. In IDC, the enzyme activities are sustained until very late in the disease.

Performance of a stentless xenograft aortic bioprosthesis up to four years after implantation.

Conventional biologic and mechanical prostheses have important limitations with regard to their hemodynamic characteristics and long-term durability. We evaluated the hemodynamic function of a stentless porcine aortic prosthesis in 10 patients by invasive pressure measurements and angiography with videodensitometry 8 +/- 4 days after operation, as well as by Doppler echocardiography 35 +/- 15 months after valve replacement. The early postoperative invasive study revealed a mean gradient of 8 +/- 6 mm Hg across the prosthesis, no regurgitation in eight patients, and mild regurgitation, defined as less than 20% regurgitant fraction, in the remaining two patients. The late postoperative Doppler echocardiographic study revealed a mean gradient across the aortic prosthesis of 6 +/- 3 mm Hg, mean Doppler-derived valve orifice area of 1.8 +/- 0.6 cm2, and color Doppler flow velocity mapping suggested no regurgitation in eight patients and mild regurgitation in two patients corresponding to early postoperative angiography. None of the 10 patients received anticoagulation therapy. The clinical course of all patients was without incident. This stentless aortic bioprosthesis may offer hemodynamic advantage; however, further studies are needed to allow comparison with conventional mechanical and biologic prostheses.

Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia.

In-vivo imaging studies and post-mortem studies have demonstrated an impairment of energy metabolism in brains of patients with schizophrenia. Decreased oxidative metabolism has been consistently documented in the frontal lobes. However, the biochemical basis of these changes is unclear. The changes could be caused by reduced requirement of the cells for metabolic energy or an abnormality in energy generation. Neurons generate energy through the respiratory chain in the mitochondria. The respiratory chain consists of five enzyme complexes (I-V). The purpose of the present study was to assess mitochondrial function and test the hypothesis of an underlying oxidative phosphorylation defect in schizophrenia. We analysed spectrophotometrically post-mortem brain specimens of frontal cortex, temporal cortex, basal ganglia, and cerebellum of 12 patients who met the DSM-IV criteria for schizophrenia and of 13 healthy controls for the specific activities of respiratory chain enzymes in the mitochondria. The major finding was that the activity of complex IV was significantly reduced in the frontal cortex (40.9+/-6.7 vs. 87.3+/-12, P=0.003) and in the temporal cortex (39.5+/-6.8 vs. 78+/-10.8, P=0.006) of schizophrenics. In addition, the activity of complexes I+III was significantly reduced in the temporal cortex (2.2+/-0.6 vs. 4.4+/-0.5, P=0.01) and basal ganglia (1.6+/-0.5 vs. 3.4+/-0.3, P=0.015) in schizophrenia. All other enzyme activities showed no differences to healthy controls. The results confirm a defect of oxidative phosphorylation in brains from patients with schizophrenia, which may contribute to impaired energy generation.

Sporicidal activity of hospital disinfectants.

The sporicidal activity of hospital disinfectants was tested using two methods of test and two species of spores. Alcoholic hypochlorite and glutaraldehyde (Cidex) showed some sporicidal activity; the first was the more effective. Iodophors, formalin, and phenolics were less effective, in descending order. Chlorhexidine showed no activity.A freshly prepared solution containing 50% methanol and sufficient sodium hypochlorite to provide 2000 parts per million available chlorine in distilled water, with a contact time of 15 minutes, is suggested for the decontamination of clean, heat-sensitive instruments except those of plated metal. It must be understood that no such method can be depended upon to sterilize.The instruments should be rinsed in sterile water before use after decontamination.

Circumferential rupture of the ascending aorta in a fusiform aneurysm.

A case of complete circumferential rupture of the ascending aorta with massive hemorrhage into the pericardial space and around the aortic arch is described. Computed tomography was used to establish the diagnosis. Rupture occurred distal to the origin of the coronary arteries without impairment of aortic valve function, and therefore a preclotted woven Dacron graft was inserted. To the best of our knowledge, this is the first documented case of complete rupture of the ascending aorta in a fusiform aneurysm and the first report of its successful surgical treatment.

Improved mitral valve replacement.

We describe a simple, reproducible technique of achieving more normal left ventricular function after mitral valve replacement. Polytetrafluoroethylene (PTFE) sutures are used as chordae tendineae to restore the integrity between the mechanical valve and papillary muscles and thus the left ventricular wall.

Aortic valve reconstruction in Rubinstein-Taybi-syndrome: the valuable aid of transesophageal echocardiography.

A fourteen year old boy with Rubinstein-Taybi-syndrome presented with a severe congenital subvalvular fibrous aortic stenosis with associated aortic regurgitation. Transthoracic echocardiographic imaging and left heart angiography showed a transvalvular peak systolic pressure gradient of 90 mmHg and a regurgitant fraction of 30%. The surgical treatment consisted of resection of the subvalvular fibrous tissue and subsequent aortic valvuloplasty. Intraoperative transesophageal echocardiography revealed a wide systolic opening of the aortic valve and good coaptation of the aortic valve leaflets in diastole. Two-dimensional color-coded and contrast echocardiography were successfully used to confirm a satisfactory reconstruction. Transesophageal echocardiography therefore represents a valuable tool in the assessment of the morphologic and haemodynamic status, especially in rare cases of congenital heart disease in older children.

Protective effect of melatonin on damage in the sperm parameters of mice exposed to diazinon / Efecto protector de la melatonina sobre el daño en los parámetros espermáticos de ratones expuestos a diazinón

Since normal sperm parameters can be altered by organophosphorous pesticides, this study intended to determine if melatonin is able to prevent the damage on sperm quality after an acute exposure to diazinon. Adult male mice were injected intraperitoneally with melatonin, diazinon (1/3 or 2/3 LD50) or both, and sperm parameters were evaluated on days 1 or 32 post injection. Groups treated with diazinon showed elevated lipid peroxidation levels on day 1 post treatment, while groups pretreated with melatonin before diazinon showed no difference compared to control. Sperm count showed a significant decrease in both diazinon-treated groups only on day 32 post injection; no differences were observed in groups pretreated with melatonin prior to diazinon compared to control. The percentage of abnormal sperm morphology increased in the diazinon-treated groups only on day 32 postinjection. The administration of melatonin prior to exposure to diazinon prevents the alteration of sperm parameters commonly caused by organophosphates, possibly due to its antioxidant properties.

Debido a que los parámetros normales de los espermatozoides pueden ser alterados por algunos contaminantes como los pesticidas organofosforados, este estudio pretende determinar si melatonina es capaz de prevenir o proteger del daño en la calidad espermática, después de una exposición aguda a diazinon. Ratones machos adultos fueron inyectados via intraperitoneal con diazinon 1/3 y 2/3 de la LD50 y otro grupo tratados con melatonina + 1/3 diazinon LD50 y melatonina + 2/3 LD50. Los parámetros espermáticos fueron evaluados al día 1 y al día 32 post tratamiento. Los grupos tratados con diazinon solo o conjugado con melatonina mostraron un incremento significativo en los niveles de lipoperoxidación en el tratamiento después de un día. Al día 32 no se observan diferencias significativas con el grupo control. El recuento espermático al día 1 no presenta diferencias entre los grupos tratados y el control. Sin embargo al día 32 los grupos tratados con diazinon solo, muestran una disminución significativa, solo el grupo de melatonina +1/3 diazinon, presenta valores similares al grupo control. La morfología espermática normal presenta una disminución significativa en grupos tratados con diazinon, pero un aumento significativo al día 32 en los grupos tratados con melatonina. Los mayores porcentajes de anormalidades se presentan en la cabeza y la cola de los espermatozoides. La administración de melatonina antes de la exposición al diazinon evita las alteraciones de los parámetros espermáticos, comúnmente causada por organofosforados, posiblemente debido a sus propiedades antioxidantes.

[Possibilities and limits of biplane transesophageal echocardiography in dissection of the thoracic aorta]. / Möglichkeiten und Grenzen der biplanen transösophagealen Echokardiographie bei der Dissektion der thorakalen Aorta.

Dissecting aneurysms of the thoracic aorta can be rapidly and accurately diagnosed by transoesophageal echocardiography. The recent advent of the transoesophageal echocardiographic probe with transverse and longitudinal imaging transducers that add orthogonal viewing planes is an important advance in the evaluation of both the anatomic and haemodynamic status of the patient. It allows a still better understanding of the pathologic changes and therefore helps in surgical decision making. With the capabilities of colour flow Doppler, biplane transoesophageal echocardiography proves to be an ideal tool for the preoperative confirmation of the suspected diagnosis, intraoperative assessment and post-operative ambulatory follow-up and should be applied whenever possible.