Effects of a toxin from the mucus of the caribbean sea anemone (Bunodosoma granulifera) on the ionic currents of single ventricular mammalian cardiomyocytes

The effects were studied of a toxin (Bainh) isolated from the secretion of the Caribbean sea anemone Bunodosoma granulifera on electrical and mechanical activities of rat ventricular muscle. The effects on the ionic currents of single rat and dog ventricular cardiomyocytes were studied using the whole-cell recording patch-clamp technique. In the concentration range from 1 to 10 mg/ml, Bainh increased the force of contraction and induced an increase in action potential duration of ventricular multicellular preparations. In single cardiomyocytes, at concentrations up to 10 mg/ml Bainh showed no significant effects on the sodium current. However, at 0.5–1 mg/ml it increased the L-type Ca current (I_CaL) by 25–50%. This increase in I_CaL was not voltage dependent and was reversible after washout. The transient outward current was not significantly affected by Bainh (1–10 mg/ml). In this concentration range, Bainh markedly (≈75%) increased the inward-going rectifier current, I_K1. This effect that was not voltage dependent and was fully reversible upon returning to control solution. It is suggested that these effects on ionic currents could explain the positive inotropic action of Bainh on cardiac multicellular preparations.     

Serotonergic receptors in the brain of in utero undernourished rats

In this study, we report that 5-HT(1A) receptors are already present in fractions of axonal growth cones, from the normal rat fetal brain (E-17). Also, in utero undernourished (UN) rat pups at birth show a noteworthy enhancement in the B(max) of [3H]5-hydroxytryptamine (5-HT) and [3H]8-hydroxy-(2-N,N-dipropilamin)-tetralin (([3H])8-OH-DPAT), in the brainstem and cerebral cortex up to the second week after birth. Afterwards, there is a significant decrease in the binding of these ligands. [125I]Cyanopindolo binding in the cerebral cortex only showed a decrease in the same period. An elevation of brain serotonin in both regions was also present. These findings together, suggest that the mechanisms of regulation of serotonergic receptors' expression during the period studied, may not depend on the amount of neurotransmitter in the synaptic cleft, because in the early UN brain it would be expected only a lower receptor's density due to the chronic serotonin increase. On this basis, we propose that developmental activation of brain serotonin biosynthesis observed in early UN animals may disrupt the mechanism regulating the expression of 5-HT receptors during development.     

Liver Transplant Recipients Older Than 60 Years Have Lower Survival and Higher Incidence of Malignancy

Older age is not considered a contraindication for liver transplantation, but age-related morbidity may be a cause of mortality. Survival and the incidence of the main post-transplant complications were assessed in 111 adult liver transplant recipients. They were divided in two groups according to their age (patients younger than 60 years, n=54; patients older than 60 years, n=57) and both groups were compared. Older patients were more frequently transplanted for hepatitis C (p= 0.03) and hepatocellular carcinoma (p= 0.05) and their liver disease was less advanced (Child-Pugh and MELD scores were significantly lower; p=0.004 and p=0.05, respectively). After transplantation, older patients had a significantly lower survival (p=0.02). Higher age was independently associated with mortality (hazard ratio for each 10-year increase: 2.1; 95% confidence interval: 1.1- 4.0; p=0.02). The incidence of de novo neoplasia and nonskin neoplasia were higher in older patients (p=0.02 and p =0.007, respectively). Malignancy was the cause of death in one patient younger than 60 years and in 12 patients older than 60 years (p =0.002). In multivariate analysis, a higher age and smoking were independently associated with a higher risk of dying of de novo neoplasia. In conclusion, older liver transplant recipients have a significantly lower survival than younger patients. Malignancy is responsible for this decreased survival.     

Phenomenology and clinical correlates of delusions in Alzheimer disease.

OBJECTIVES: The objectives of this study were to determine whether anosognosia, depression, and elevated mood are associated with delusions in Alzheimer disease (AD), and to examine the validity of standardized diagnostic criteria for psychosis of dementia. METHOD: The authors assessed a consecutive series of 771 patients with AD attending a dementia clinic with a comprehensive neuropsychologic and psychiatric evaluation that included specific measures of delusions, hallucinations, anosognosia, depression, and elevated mood. RESULTS: Delusions were found in one-third of the patients and hallucinations in 7%. Most patients with hallucinations also had delusions. A principal component analysis of the Psychosis Dementia Scale, which rates the presence and severity of delusions, produced the factors of paranoid misidentification and expansive delusions. Paranoid, but not expansive, delusions increased across the stages of the illness. Anosognosia and depression were significantly and independently associated with the presence of delusions, whereas elevated mood was significantly associated with expansive, but not paranoid, delusions. A multiple logistic regression analysis demonstrated that delusions in AD were significantly associated with depression, anosognosia, overt aggression, and agitation. CONCLUSIONS: Anosognosia, depression, global cognitive deficits, and elevated mood are the main psychiatric correlates of paranoid misidentification and expansive delusions in AD, whereas overt aggression and agitation are the most frequent behavioral concomitants of psychosis in AD.     

Transient Facial Palsy in Sphenoidal Electrode Placement

Summary: Purpose: Sphenoidal electrode (SE) insertion can cause pain, for which local anesthesia with lidocaine or intravenous administration of fentanyl has been advocated by different epilepsy treatment centers. Transient facial palsies have been observed after SE insertion. Their frequency of occurrence, distribution, and duration have not been well characterized, however. We hypothesized that this complication is due to the effect of local anesthesia on the peripheral branches of the seventh cranial nerve. To test this hypothesis, we compared the incidence and characteristics of facial palsy during SE insertions performed with either local anesthesia or after intravenous fentanyl administration.
Methods: We performed a retrospective study in two patient groups. Group A consisted of 25 patients aged 28 ± 8·2 years who underwent a prolonged video-EEG (VEEG) monitoring study with SE after subcutaneous infusion of 1% lidocaine in the insertion area. Group B included 25 patients aged 30·1 ± 8·9 years whose SE were inserted after intravenous administration of 100-200 μ fentanyl. Blood pressure (BP) was monitored every 3-5 min throughout the procedure.
Results: Five patients (20%) from group A had a transient facial palsy; in 4, it was complete and in 1 it was partial; 1 patient had a bilateral facial palsy. Paresis lasted 1-7 min (mean 3·2 min). In all patients, the recovery was complete. None of the patients in group B had complications (p = 0·025, Fisher's exact test).
Conclusions: Transient facial palsy is a relatively frequent complication of SE insertion when SE are placed under local anesthesia; patients should be forewarned of its possible occurrence.     

Neurocysticercosis in Persons with Epilepsy in Medellín,Colombia

Summary: Purpose: A prospective series of 643 persons with epilepsy attending a reference neurologic center in Medellin, Colombia, was examined by computed tomography (CT scan) or serology or both with the enzyme-linked immunoelectrotransfer blot assay (EITB) to assess the prevalence of Taenia solium cysticercosis. Methods: All presenting patients were consecutively enrolled in the study. Five hundred forty-six persons underwent cerebral CT scans; 376 of them also had serum EITB performed. Results: Prevalence of neurocys@ercosis by CT scan was 13.92%. Overall prevalence of T. solium antibodies with EITB was 9.82%, but for those with late-onset epilepsy (onset after age 30 years), prevalence increased to 17.5% and 19% for those who originated from outside urban Medellin. Seroprevalence in individuals with mixed lesions (cysts and calcifications) was 88.2% and 64.10% in those with live cysts. Conversely, only 2.72% of persons with CT findings not related to neurocysticercosis had positive EITB tests. Conclusions: Our study shows that an important proportion of individuals with epilepsy have radiologic or serologic evidence of T. solium infection, suggesting that neurocysticercosis is an important etiology for epilepsy in Colombia.     

Dexamethasone in the treatment of meningeal leukemia

To determine if dexamethasone has a role in the treatment of meningeal leukemia, 8 consecutive patients with acute lymphoblastic and signs or symptoms of CNS were included in the study. After the confirmation of leukemic blast cells on cerebrospinal fluid, they received intrathecal and IV dexamethasone; 3 days later the patients received “triple” intrathecal chemotherapy with dexamethasone, methotrexate and cytarabine, and the spinal fluid was studied again. All patients had good clinical response and 7 out of the 8 patients showed reduction on the CSF cell count after the use of dexamethasone alone. The results suggest that dexamethasone is a lympholytic agent that could play a more active role in the prevention and therapy of meningeal leukemia and should be preferred over hydrocortisone in the so called “triple” intrathecal chemotherapy for the prevention and treatment of CNS leukemia. © 1995 Wiley-Liss, Inc.     

Schedule-dependency of in vivo modulation of 5-fluorouracil by leucovorin and uridine in murine colon carcinoma

Summary The effect of leucovorin (LV) given in various doses and schedules on the in vivo antitumor activity and toxicity of 5-fluorouracil (5FU) was studied in two murine colon cancer lines, i.e., Colon 26 (relatively resistant to 5FU) and Colon 38 (5FU sensitive), maintained in Balb-c and C57B1/6 mice, respectively. Mice were treated weekly with 5FU at the maximum tolerated dose, alone and in combination with LV. In Colon 26, neither simultaneous administration of 5FU and LV nor 5FU combined with delayed administration of LV potentiated the antitumor activity of 5FU. LV given twice — 1 hr before (50 mg/kg) and then together (50 mg/kg) with 5FU (100 mg/kg) — gave significantly better delay of tumor growth of both tumor lines than 5FU did alone (100 mg/kg). No differences were found after a total LV dose of 100 or 200 mg/kg. Delayed administration of uridine (3500 mg/kg) allowed the use of higher 5FU doses, which improved the antitumor effect on Colon 26. Systemic toxicity led to moderate weight loss in treated mice, but was comparable for mice treated with 5FU alone or combined with LV. Hematological toxicity consisted of moderate leukopenia (nadir 40%), which was observed with the most active schedule and was less severe than with 5FU alone. This schedule did not cause thrombocytopenia, but after discontinuation the thrombocyte count showed an overshoot. Addition of uridine to this schedule reduced hematological toxicity only slightly. It is concluded that LV potentiated the antitumor activity of 5FU against two solid tumor lines, i.e., a relatively resistant and a sensitive murine colon carcinoma, and that toxicity was moderate.Abbreviations 5FU 5-fluorouracil - LV leucovorin (folinic acid, 5-formyl-tetrahydrofolate) - FdUMP 5-fluoro 2-deoxyuridine 5monophosphate - TS thymidylate synthase - CH2-THF 5-10 methylenetetrahydrofolate - UR uridine - GDF growth delay factor - TD tumor doubling time - MTD maximum tolerated dose - T/C mean tumor volume of treated mice divided by mean tumor volume of control mice     

Haplotype diversity and somatic instability in normal and expanded SCA8 alleles.

Spinocerebellar ataxia type 8 (SCA8) is an autosomal dominant late-onset neurodegenerative disorder, belonging to the group of diseases caused by trinucleotide repeat expansions. SCA8 remains one of the most intriguing SCAs, regarding the reduced disease penetrance, and the high instability and poorly understood functional meaning of the (CTA)(n)(CTG)(n) expansion. We performed haplotype and sequencing analysis in a large region, encompassing the repeat, in four SCA8 and 20 control Portuguese families. The results from the haplotype study including the combined repeat and six SNP markers showed two different haplotypes, AG-Exp-GTTG and AG-Exp-CTTG, in the SCA8 families. Among the control population, these were also the most frequent, in a total of five haplotypes found unequally distributed throughout repeat sizes. From cloning fragments of control, unstable normal and expanded chromosomes, eleven different base substitutions were identified in exon A of the SCA8 gene. In some instances, somatic variability in repeat size or base composition was found for a same chromosome, regardless of its normal or expanded nature. In conclusion, our results in Portuguese families with ataxia show that SCA8 expansions arose in common backgrounds; in addition, this region seems to be unstable beyond the repeat.