Hereditary Hypertriglyceridemic Rat: A New Animal Model of Metabolic Alterations in Hypertension

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerrance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na⁺ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.     

Neuquen,Argentina: Provincial Health Policies and Their Results*

ABSTRACT: A case study of the creation and implementation of a four-tier, integrated system of health care services in a sparsely populated, rural province in Argentina is described and discussed. Begun in 1970 in a diverse geographical area with a tradition of poor health status and inadequate health care resources, the provincial government set out to develop the human, physical and technological resources needed to provide a system of preventive and curative services appropriate to the health care needs of its residents. Innovative programs included training in management techniques, and epidemiological perspective of high risk, an emphasis on personnel development through a rural general medicine residency and an expanded nursing program as well as programs to attack infectious diseases, poor sanitation and dental problems were all developed in response to the distinctive features of the physical and social environment of the province. Improvements in traditional health indicators are reviewed and attributed to the program and administrative structures that were developed.     

Ontogenetic Development of 5-HT1D Receptors in Human Brain: An Autoradiographic Study

The pattern of pre- and postnatal appearance of 5-HT_1D receptors throughout the different areas of the human brain was studied by quantitative in vitro autoradiography, using [¹²⁵I]GTI (serotonin O -carboxymethyl-glycyl-[¹²⁵I]tyrosinamide) as a ligand. The anatomical distribution of 5-HT_1D receptors in neonatal, infant and children's brain was in good agreement with that observed in the adult, the basal ganglia and substantia nigra being the most intensely labelled areas. The development of these receptors throughout the human brain was mainly postnatal: low densities of [¹²⁵I]GTI binding sites were observed at the fetal/neonatal stage in most regions analyzed, in contrast with the high levels of labelling found in infant and children's brains. Indeed, in a number of regions, including the globus pallidus, substantia nigra and visual cortex, a peak of overexpression of 5-HT_1D receptors was observed in the first decade of life. Such overexpression could support a regulatory role for 5-HT_1D receptors in advanced periods of the CNS developmental process. Our results also indicate that the administration of drugs acting on 5-HT_1D receptors during the early postnatal period of life could result in modifications of their properties, as these receptors are already functional in this period.     

Sleep complaints and their relation with drug treatment in patients suffering from Parkinson's disease.

The aim of this research was to quantify sleep problems in patients suffering from Parkinson's disease by means of the new Parkinson's Disease Sleep Scale (PDSS) and to correlate such problems with the possible influence of current drug treatment. A total of 70 patients (36 men and 34 women) with a diagnosis of Parkinson's disease were enrolled. Their mean age was 69.7 +/- 8.2 years, and duration of disease was 7.4 +/- 4.8 years. All patients completed the PDSS and the Unified Parkinson's Disease Rating Scale (UPDRS Parts I-IV). Drug consumption and doses were registered. The mean score on the PDSS scale was 109.23 +/- 19.75 and on the UPDRS III scale was 25.24 +/- 11.35. The lowest scores were obtained in Item 3 (sleep fragmentation): 5.53 (2.46); and in Item 8 (nocturia): 5.75 (2.91). There was a weak correlation between the PDSS and UPDRS III (cc = -0.355, P = 0.003), PDSS and UPDRS I (cc = -0.272, P = 0.02), and PDSS and UPDRS IV (cc = -0.416, P < 0.001). Motor conditions, mental state, and drug complications influence sleep quality. Although this effect was significant, it was not of a great magnitude. Dopaminergic drugs did not increase daytime sleepiness. As a whole, sleep quality in patients who took dopaminergic agonists did not differ from that of patients who took levodopa in monotherapy.     

Loss of heterozygosity for distal markers on 22q in human gliomas.

Loss of constitutional heterozygosity as determined through the analysis of restriction-fragment-length polymorphism (RFLP) on tumoral and constitutional DNA has proven to be helpful to delimit the location of tumor-suppressor genes in the human genome. In malignant gliomas this approach indicates that chromosomes 9p, 10, 17p, and 22 may contain genes of this category involved in its origin and/or progression. Regarding chromosome 22, the data so far provided by molecular studies confirmed those previously reported by cytogenetic studies, suggesting the existence of a sub-group of malignant gliomas characterized by monosomy of this chromosome. However, the precise location of the putative glioma suppressor gene on chromosome 22 remains ambiguous. We have performed a combined cytogenetic and RFLP study on a series of 31 gliomas, looking for structural abnormalities of this chromosome. In 3 instances, terminal deletions of the long arm of chromosome 22 were observed by both methodologies, suggesting that the band q13 region distal to the D22S80 marker might be the critical domain non-randomly involved in tumor suppression of gliomas.     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Auditory event-related potentials and cognitive function of preterm children at five years of age.

OBJECTIVE: In our previous study, auditory event-related potentials (AERPs) in preterm 1-year-old children had a positive deflection at 150-350 ms that correlated positively with their 2-year neurodevelopmental outcome. In a study of the same subjects at age 5, our aim was to assess AERPs and their relationship to neuropsychological test results. METHODS: Preterm small (SGA, n=13), appropriate for gestational age (AGA, n=15), and control (n=13) children were assessed with an Easy paradigm presenting a large frequency change accompanied with occasional novel sounds, and a Challenging paradigm presenting small frequency and duration changes with a rapid rate. The preterm children underwent neurocognitive tests. RESULTS: Easy paradigm. The P1 response to frequency deviant was smaller and MMN larger in the preterm than in the control children. Challenging paradigm. The P1 response to standard, frequency, and duration deviants was smaller in the preterm than in the control children. The N2 response to frequency deviant was larger in the preterm than in the control children. AGA and SGA children had similar AERPs. The P1, N2, and MMN amplitudes correlated with verbal IQ and NEPSY language subtests. CONCLUSIONS: Small P1 response(s) appears to be typical for preterm children. SIGNIFICANCE: Small P1 response in preterm children may suggest altered primary auditory processing.     

The incidence of error in young children's Wh-questions.

Many current generativist theorists suggest that young children possess the grammatical principles of inversion required for question formation but make errors because they find it difficult to learn language-specific rules about how inversion applies. The present study analyzed longitudinal spontaneous sampled data from twelve 2-3-year-old English speaking children and the intensive diary data of 1 child (age 2;7 [years;months] to 2;11) in order to test some of these theories. The results indicated significantly different rates of error use across different auxiliaries. In particular, error rates differed across 2 forms of the same auxiliary subtype (e.g., auxiliary is vs. are), and auxiliary DO and modal auxiliaries attracted significantly higher rates of errors of inversion than other auxiliaries. The authors concluded that current generativist theories might have problems explaining the patterning of errors seen in children's questions, which might be more consistent with a constructivist account of development. However, constructivists need to devise more precise predictions in order to fully explain the acquisition of questions.