Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice

Background and purpose:

W/W^v and wild-type murine bladders were studied to determine whether the W/W^v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Experimental approach:

Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.

Key results:

Wild-type and W/W^v detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/W^v detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/W^v strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both tissue types. Wild-type and W/W^v detrusors had similar resting membrane potentials of −48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/W^v preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both preparations.

Conclusions and implications:

Bladders from W/W^v mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/W^v and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/W^v strain may not be the best model to study ICC function in the bladder.     

The Health of Older Mexican Americans in the Long Run

Objectives. We compared risk for several medical illnesses between immigrant and US-born older Mexican Americans to determine the relationship between functional health and years of US residency among immigrants.Methods. Cross-sectional, multistage probability sample data for 3050 Mexican Americans aged 65 years or older from 5 US southwestern states were analyzed. Self-rated health, medical illnesses, and functional measures were examined in multivariate regression models that included nativity and years of US residency as key predictors.Results. Self-rated health and medical illnesses of immigrant and US-born groups did not differ significantly. Immigrants with longer US residency had significantly higher cognitive functioning scores and fewer problems with functional activities after adjustment for predisposing and medical need factors.Conclusions. Among older Mexican Americans, immigrant health advantages over their US-born counterparts were not apparent. Immigrants had better health functioning with longer US residency that may derive from greater socioeconomic resources. Our findings suggest that the negative acculturation–health relationship found among younger immigrant adults may become a positive relationship in later life.More than 30 years ago, Teller and Clyburn reported more favorable birth outcomes in Bexar County, Texas, for Spanish-surnamed residents than for non-Latino White and African American residents.¹ Despite the disadvantaged economic and social position of many Latinos, additional reports appeared of unexpected favorable birth and longevity outcomes for Latinos (primarily Mexican Americans) compared with other ethnic groups.^2–5 These findings were considered paradoxical, since they ran contrary to the negative socioeconomic health gradient documented in the public health literature.^6,7 The Latino health paradox contends that despite experiencing disproportionate exposure to risk factors for excess morbidity and mortality associated with low socioeconomic position, Latinos, primarily Mexican American immigrants, generally have more favorable health outcomes than Mexican Americans born in the United States, most other minorities, and nonminorities.⁸ The longer these healthy immigrants resided in the United States and acculturated, the more likely they were to report deterioration in health status indicators compared with recent immigrants.⁹The mental health researchers Rogler et al. referred to “acculturation as an exogenous force shaping the conditions for the rise to psychological distress.”^10(p588) This phenomenon was later coined the “acculturative stress” hypothesis and widely used in mental health research of the Latino population. However, acculturative stress models have important limitations in health research because they confound the effects of cultural change on health behaviors with pathology. In addition, they are temporally unspecific and thus inconsistent with developmental models of health. We offer an alternative, the “acculturation–health” hypothesis, to emphasize that health outcomes are instead conditional on multiple life-course contingencies that vary in importance as determinants over one''s life span. The temporal relationships between acculturation and health can range from negative to positive during the lifespan of an individual. Although the negative effects of acculturation are commonly described in the literature, positive outcomes are observed as well and also require explanations.^11–15 Acculturative stress assumes a cumulative, linear, dose–response association of acculturation with health. An acculturation–health hypothesis accounts for transactions between endogenous (individual-level) and exogenous (external) factors that affect health differentially over the life course. These factors are systematically influenced by acculturation across multiple domains of life activity.The proposed acculturation–health model assumes that there are multiple points in the life course that are critical for improving health and lowering the risk of weathering effects seen in aging among minority groups.¹⁶ Carefully focused research could lead to timely and effective interventions that improve health outcomes across the life course. The assumption that a constant acculturation–health relationship is generally negative and leads to declines in health among Mexican Americans is limiting because it is overly deterministic and restricts opportunities for identifying determinants of long-range outcomes and life-course stages when they are most consequential. Although we can assume that living in a new society introduces behavioral, social, and environmental changes that may negatively influence health, there may be benefits as well, such as acquisition of new occupational skills, greater exposure to public health information, and use of preventive medicine. Nevertheless, it is unclear how these changes are expressed in the long run in the health of older Mexican Americans.Mexican Americans represent more than two-thirds of US Latinos and, perhaps accordingly, most previous studies have focused on the relationship between Mexican American acculturation (or various proxies of acculturation, such as language preference and years of US residency) and health.¹⁷ For younger Mexican Americans, most studies have reported negative relationships between acculturation and health¹¹—for example, for birth outcomes^18,19 and perinatal health behaviors,^20,21 general health behaviors (e.g., nutrition and physical exercise),²² vascular disease risks (e.g., diabetes),^23,24 and substance abuse and mental disorders.^25,26 Several reports have shown positive associations between acculturation and higher use of preventive medical services, which may relate to the higher economic position of more acculturated and US-born Mexican Americans.^27–30 Among older adults, the prevalence of depression and dementia are reportedly lower among acculturated Mexican Americans.^12,13 Furthermore, there is evidence that greater social assimilation, as evidenced by English-language acquisition and more years of education, are associated with lower disability rates and higher self-esteem.^14,15,31These general findings have led scientists to hypothesize that immigrants are somehow healthier than US-born Mexican Americans and non-Latino Whites and that with longer US residency, acculturation erodes immigrants'' health.^9,32 The negative aspects of the acculturation–health relationship dominate current thinking about Mexican American health, especially regarding acculturation-related changes in risk behaviors such as diet, exercise, and substance abuse.³³ However, if the association between acculturation and health is conditional and predicated on various endogenous and exogenous life-course factors, recent work among older adults may better inform us about the long-term acculturation–health relationship.Our first aim was to examine whether the “healthy immigrant” phenomenon persists among older Mexican Americans by comparing the rates of several medical conditions between US-born and immigrant groups. Second, we sought to determine if functional health was negatively associated with longer exposure to the host country within a representative sample of immigrant Mexican Americans. On the basis of previous work,^12–14,31 we expected that the health status of US-born and immigrant older Mexican Americans would not differ. Third, we sought to examine if longer US residency would be associated with better functional health among older Mexican American immigrants. We expected that increased wealth, access to healthcare and services would facilitate or mediate better health functioning.^6,34,35 Finally, in examining the health of older Mexican Americans, we aimed to compare the acculturative stress hypothesis and the acculturation–health hypothesis for a better understanding of their utility for the study of health.     

A profile of the online dissemination of national influenza surveillance data

Background  

Influenza surveillance systems provide important and timely information to health service providers on trends in the circulation of influenza virus and other upper respiratory tract infections. Online dissemination of surveillance data is useful for risk communication to health care professionals, the media and the general public. We reviewed national influenza surveillance websites from around the world to describe the main features of surveillance data dissemination.     

Tyrosine hydroxylase cells appearing in the mouse striatum after dopamine denervation are likely to be projection neurones regulated by L-DOPA

Tyrosine hydroxylase (TH)-immunoreactive (ir) neurones are detected in the striatum of animals after dopamine depletion and also in human parkinsonian patients. Although there is extensive evidence for TH-ir neurones in the lesioned rodent striatum, there are few details regarding the molecular phenotype of these neurones, regulation of their TH expression after l -3,4-dihydroxyphenylalanine (L-DOPA) treatment and their function. In the present study, we examined the time-course of appearance of TH-ir neurones in the mouse striatum after 6-hydroxydopamine (6-OHDA) lesion and determined their molecular phenotype. We found that TH-ir neurones appeared in the striatum as early as 3 days after a 6-OHDA lesion. By 1 week after the lesion, the number of TH-ir neurones started to decrease and this decrease progressed significantly over time. Treatment with L-DOPA increased both the number of TH-ir neurones and the intensity of their immunolabelling. The TH-ir neurones that appear after the 6-OHDA lesion in the striatum are not newly generated cells as they did not incorporate 5-bromo-2-deoxyuridine. We found that the vast majority of TH-ir neurones colocalized with dynorphin and enkephalin, suggesting that they are projection neurones of the direct and indirect striatal output pathways. TH-ir neurones did not express the dopamine transporter but half of them expressed amino acid decarboxylase, an enzyme required for dopamine synthesis. Finally, striatal TH-ir neurones are functionally active, expressing the neuronal activation marker FosB in response to L-DOPA treatment. Promotion of these striatal TH-ir neurones may be beneficial in Parkinson's disease, particularly in the early stages when dopamine denervation is incomplete.     

Parathyroid adenomas evaluated by Tl-201/Tc-99m pertechnetate subtraction scintigraphy and high-resolution ultrasonography

Thallium-201/technetium-99m pertechnetate subtraction scintigraphy of the parathyroid glands was performed in a prospective study of 33 patients who had undergone bilateral neck exploration for elevated serum calcium and serum parathyroid hormone levels. In 31 cases, the Tl-201/Tc-99m subtraction technique yielded an overall sensitivity of 81%, specificity of 99%, and accuracy of 94% for identifying solitary parathyroid adenomas. Tl-201/Tc-99m subtraction scintigraphy correctly identified 73% of parathyroid adenomas weighing less than 499 mg, 79% of those weighing 500-1,499 mg, and 100% of adenomas weighing more than 1,500 mg. In a subgroup of 24 patients with solitary parathyroid adenomas who underwent both scintigraphy and high-resolution sonography, the sensitivity, specificity, and accuracy of both procedures were similar.     

Beta-amyloid25-35 inhibits glutamate uptake in cultured neurons and astrocytes: modulation of uptake as a survival mechanism

Glutamate transporters are vulnerable to oxidants resulting in reduced uptake function. We have studied the effects of beta-amyloid(25-35) (beta A(25-35)) on [(3)H]-glutamate uptake on cortical neuron or astrocyte cultures in comparison with a scrambled peptide (SCR) and dihydrokainic acid (DHK), a prototypic uptake inhibitor. beta A(25-35) was more potent than DHK in inhibiting glutamate uptake and the effects of both were more marked on astrocytes than on neurons. At 24 h, beta A(25-35) dose-dependently (0.5-15 microM) increased glutamate levels in media from neuron cultures. DHK only enhanced extracellular glutamate at the highest concentration tested (2500 microM). beta A(25-35) induced gradual neurotoxicity (0.1-50 microM) over time. Exposure to beta A(25-35) resulted in increased uptake in astrocytes (0.25-5 microM) and neurons (0.5-15 microM) surviving its toxic effects. However, exposure to DHK (2.5-2500 microM) did not induce neurotoxicity nor modulated uptake. These results indicate that, while inhibition of glutamate uptake may be involved in the neurotoxic effects of beta A(25-35), enhancement of uptake may be a survival mechanism following exposure to beta A(25-35).