Immunohistochemical localization of substance P and substance P receptor (NK1) in the olivary pretectal nucleus of the rat

The olivary pretectal nucleus (OPN) is the first central nucleus in the pupillary light reflex arc (PLR). Substance P (SP) is a neuropeptide present in the OPN. The present immunohistochemical study, performed at the ultrastructural level, aimed to determine the synaptic localization of SP and SP receptor in the OPN. Three types of SP-positive terminals were found. The most abundant type was of retinal origin, characterized by electron-lucent mitochondria and round vesicles, organized in glomerular structures, making asymmetric synaptic contacts with dendrites, and profiles containing pleomorphic vesicles, also making synaptic contacts with dendrites. The second type of SP-immunoreactive terminal contained electron-dense mitochondria and pleomorphic vesicles. This type made symmetric synaptic contacts and may originate from the ventral part of the lateral geniculate nucleus. The third type of SP-immunoreactive terminals contained electron-dense mitochondria, clear round vesicles, and made an asymmetric synaptic contact. This type originates from the contralateral OPN. SP receptors of the NK1 subtype were revealed to be on dendrites and were part of the glomerular-like arrangement. On account of the present observations, it can be concluded that retinal projections to the OPN use SP as a neuromodulator and synapse on NK1 receptor-containing dendrites of large neurons projecting to the Edinger-Westphal nucleus. Since SP also modulates the parasympathetic component of the PLR, we postulate that SP plays a modulating role in all components of the PLR.     

Chemosensitization of myeloma plasma cells by an antisense-mediated downregulation of Bcl-2 protein.

An antisense oligodeoxynucleotide (ODN) complementary to the first six codons of the Bcl-2 mRNA, G3139 (oblimersen sodium; Genasense), has been shown to downregulate Bcl-2 and produce responses in a variety of malignancies including drug-resistant lymphoma. Incubation of ex vivo purified plasma cells from patients with multiple myeloma (MM) with carboxyfluorescein (FAM)-labeled antisense ODNs resulted in a time- and dose-dependent uptake in the cytoplasm and nucleus. No major differences in uptake of Bcl-2 antisense ODNs were observed among patients' samples. Incubation of purified myeloma plasma cells with G3139, but not solvent or reverse polarity control ODNs, resulted in a reduction (>75%) of Bcl-2 mRNA levels after 2 and 4 days, as measured by Real-Time PCR. Treatment with G3139 led to a sequence-specific reduction of Bcl-2 protein levels within 4 days of exposure in 10 out of 11 clinical samples from patients with chemosensitive and multidrug-resistant disease, without significant reduction of alpha-Actin, Bax, Bcl-XL, or Mcl-1 proteins. This resulted in a significantly enhanced sensitivity of the myeloma tumor cells to dexamethasone or doxorubicin-induced apoptosis. G3139 can consistently enter myeloma cells, downregulate the expression of Bcl-2, and enhance the efficacy of myeloma therapy. These data support further clinical evaluation of G3139 therapy in multiple myeloma.     

Immunocytochemical localization of the glutamate transporter GLT-1 in goldfish (Carassius auratus) retina

Glutamate is the major excitatory neurotransmitter in the retina of vertebrates. Electrophysiological experiments in goldfish and salamander have shown that neuronal glutamate transporters play an important role in the clearance of glutamate from cone synaptic clefts. In this study, the localization of the glutamate transporter GLT-1 has been investigated immunocytochemically at the light and electron microscopical levels in the goldfish retina using a GLT-1-specific antibody. GLT immunoreactivity (IR) was observed at the light microscopical level in Müller cells, bipolar cells, the outer plexiform layer (OPL), and the inner plexiform layer (IPL). At the electron microscopical level, membrane-bound and cytoplasmic GLT-IR in the OPL was located in finger-like protrusions of the cone terminal located near the invaginating postsynaptic processes of bipolar and horizontal cells. GLT-IR was not observed in the vicinity of synaptic ribbons. This location of GLT-1 allows modulation of the glutamate concentration in the synaptic cleft, thereby shaping the dynamics of synaptic transmission between cones and second-order neurons. In the inner IPL, GLT-IR was observed in the cytoplasm and was membrane bound in mixed rod/cone bipolar cell terminals and cone bipolar cell terminals. The membrane-bound GLT-1 was generally observed at some distance from the synaptic ribbon. The morphology of the bipolar cell terminal together with the localization of GLT-1 suggests that at least these glutamate transporters are not primarily involved in rapid uptake of glutamate release by the bipolar cells. The GLT-IR in the cytoplasm of Müller cells was located throughout the entire goldfish retina from the outer limiting membrane to the inner limiting membrane. The location of GLT-1 in Müller cells is consistent with the role of Müller cells in converting glutamate to glutamine.     

Depressive symptoms as risk factor of cardiovascular mortality in older European men: the Finland, Italy and Netherlands Elderly (FINE) study.

BACKGROUND: Depressive symptoms have been suggested to increase the risk of cardiovascular diseases, but this may reflect reversed causality. We investigated to what extent depressive symptoms are a true risk factor for cardiovascular mortality in elderly men. DESIGN: The Finland, Italy and Netherlands Elderly (FINE) study is a prospective cohort study conducted in Finland, Italy and The Netherlands. METHODS: Depressive symptoms were measured with the Zung self-rating Depression Scale in 799 elderly men, aged 70-90 years, free from cardiovascular diseases. Using Cox models, hazard ratios (HRs) were calculated for specific cardiovascular mortality endpoints. The analyses were adjusted for potential confounders, stratified on country and repeated after exclusion of men who died from cardiovascular diseases up to 5 years after baseline. RESULTS: During 10-years of follow-up 224 (28%) men died from cardiovascular diseases. The adjusted hazard for a five-point increase in depressive symptoms was 1.15 [95% confidence interval (CI) 1.08-1.23] for cardiovascular mortality. This risk was stronger for mortality from stroke (HR 1.35; 95% CI 1.19-1.53) and heart failure (HR 1.16; 95% CI 1.00-1.35) in comparison with mortality from coronary heart disease (HR 1.08; 95% CI 0.97-1.20) and other degenerative heart diseases (HR 1.06; 95% CI 0.91-1.23). Exclusion of men who died from cardiovascular diseases within 5 years after baseline did not change the strength of the associations. There were no significant differences in HRs between northern and southern Europe. CONCLUSIONS: This study provides further and more convincing prospective evidence for depressive symptoms as a risk factor for cardiovascular mortality in elderly men.     

Does cultural capital contribute to educational inequalities in food consumption in the Netherlands? A cross-sectional analysis of the GLOBE-2011 survey

Background

The importance of culture for food consumption is widely acknowledged, as well as the fact that culture-based resources (“cultural capital”) differ between educational groups. Since current explanations for educational inequalities in healthy and unhealthy food consumption (e.g. economic capital, social capital) are unable to fully explain this gradient, we aim to investigate a new explanation for educational inequalities in healthy food consumption, i.e. the role of cultural capital.

Methods

Data were obtained cross-sectionally by a postal survey among participants of the GLOBE study in the Netherlands in 2011 (N?=?2953; response 67.1%). The survey measured respondents’ highest attained educational level, food-related cultural capital (institutionalised, objectivised and incorporated cultural capital), economic capital (e.g. home ownership, financial strain), social capital (e.g. social support, health-related social leverage, interpersonal relationships), and frequency of consumption of healthy and unhealthy food products. Two general outcomes (overall healthy food consumption, and overall unhealthy food consumption), and seven specific food consumption outcomes were constructed, and prevalence ratios (PR) were estimated in Poisson regression models with robust variance.

Results

Cultural capital was significantly associated with all food outcomes, also when social and economic capital were taken into account. Those with low levels of cultural capital were more likely to have a lower overall healthy food consumption (PR 1.35, 95% CI 1.22–1.49), a lower consumption of whole wheat bread (PR 1.21, 95% CI 1.05–1.38), vegetables (PR 1.55, 95% CI 1.40–1.71), and meat-substitutes and fish (PR 1.74, 95% CI 1.53–1.97), and a higher consumption of fried food (PR 1.59, 95% CI 1.31–1.93). Social capital was positively associated with overall healthy food consumption, whole wheat bread consumption, and the consumption of fish and meat-substitutes, and economic capital with none of the outcomes. The PR of the lowest educational group to have a low overall healthy food consumption decreased from 1.48 (95% CI 1.28–1.73) to 1.22 (95% CI 1.04–1.43) when cultural, social and economic capital were taken into account.

Conclusions

Cultural capital contributed to the explanation of educational inequalities in food consumption in The Netherlands, over and above economic and social capital. The socialisation processes through which cultural capital is acquired could offer new entry-points for the promotion of healthy food consumption among low educational groups.

     

Disease-related difficulties and satisfaction with level of knowledge in adults with mild or complex congenital heart disease

OBJECTIVES: To evaluate difficulties in daily life, and satisfaction with level of knowledge about their disease, in patients with congenital cardiac disease in order to improve counselling. METHODS: A self-administered questionnaire was completed by 80 patients with mild, and 76 with complex, congenital cardiac disease. They were aged from 17 to 32 years. RESULTS: Even patients with only mild malformations experienced difficulties related to their disease, but being found in only 11%, these were significantly less than those uncovered in 87% of those with complex disease (p < 0.001). Those patients with complex malformations frequently felt restricted in choices because of their disease in areas such as sport (59%), employment (51%), and education (34%). Other difficulties reported were: paying a higher premium for life insurance (29%), having to give up on a sport (28%), and being excluded from a job (18%). Depending on the item, between one-fifth and two-thirds of participants reported gaps in knowledge, most frequently for "causes of congenital cardiac disease", "future consequences", and "family planning". For 53% of those with mild anomalies, and 93% of severely affected patients, the cardiologist is the most important source of information. CONCLUSIONS: A minority of adults with mild, and a majority of those with complex congenital cardiac disease report difficulties in daily life. A substantial number of these patients feel that they have an inadequate level of knowledge about their disease. Our results suggest the need for a specific programme of counselling.     

Calcium and Vitamin D in Sarcoidosis: Is Supplementation Safe?

Granulomas in sarcoidosis express high levels of 1α‐hydroxylase, an enzyme that catalyzes the hydroxylation of 25‐OH vitamin D to its active form, 1,25(OH)₂ vitamin D. Overproduction of 1α‐hydroxylase is held responsible for the development of hypercalcemia in sarcoidosis patients. Corticosteroids are used as first‐line treatment in organ‐threatening sarcoidosis. In this light, osteoporosis prevention with calcium and vitamin D (CAD) supplementation is often warranted. However, sarcoidosis patients are at risk for hypercalcemia, and CAD supplementation affects the calcium metabolism. We studied calcium and vitamin D disorders in a large cohort of sarcoidosis patients and investigated if CAD supplementation is safe. Retrospectively, data of 301 sarcoidosis patients from July 1986 to June 2009 were analyzed for serum calcium, 25‐hydroxy vitamin D (25‐(OH)D), 1,25‐dihydroxy vitamin D (1,25(OH)₂D), and use of CAD supplementation. Disease activity of sarcoidosis was compared with serum levels of vitamin D. Hypercalcemia occurred in 8%. A significant negative correlation was found between 25‐(OH)D and disease activity of sarcoidosis measured by somatostatin receptor scintigraphy. In our study, 5 of the 104 CAD‐supplemented patients developed hypercalcemia, but CAD supplementation was not the cause of hypercalcemia. Patients without CAD supplementation were at higher risk for developing hypercalcemia. During CAD supplementation, no hypercalcemia developed as a result of supplementation. Hypovitaminosis D seems to be related with more disease activity of sarcoidosis and, therefore, could be a potential risk factor for disease activity of sarcoidosis. Thus, vitamin D–deficient sarcoidosis patients should be supplemented. © 2014 American Society for Bone and Mineral Research.     

Secondary infertility as a late complication of vesico-amniotic shunt therapy

OBJECTIVE: Vesico-amniotic shunting can be used for the treatment of fetal obstructive uropathy. However, the procedure is associated with a significant risk of complications. We report a case of a complicated vesico-amniotic placement, where a vesico-amniotic shunt ultimately resulted in, fortunately reversible, infertility. CASE: A 36-year-old multigravida was referred to our center at 13 weeks' gestation for the evaluation of fetal lower urinary obstruction. A vesico-amniotic shunt placement requiring several attempts was performed. A few weeks later premature rupture of the membranes occurred. At the request of the parents, the pregnancy was terminated at 22 weeks'gestation. The patient visited us again for secondary infertility, which turned out to be caused by a shunt left behind in the uterus, acting as an IUD. After hysteroscopic removal, she soon became pregnant again. CONCLUSION: This case illustrates the importance of careful documentation relating to each and every operation, of all materials used and what was retained in the patient. At delivery, obstetric staff should be completely aware of the prenatal treatment procedures performed, to ensure that no foreign objects are left by oversight, inside the patient's body.     

Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis

Objective

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease involving chronic arthritis. The clinical course is characterized by a fluctuating pattern of active and inactive disease. We have described in detail the clinical course in different JIA subtypes during the first 2 years after diagnosis and studied its relationship to disease activity in the following years.

Methods

Detailed clinical data on different parameters describing the disease activity in sequential time periods covering the first 2 years after diagnosis were retrieved from the charts of 311 patients with JIA and compared between subtypes. In a cohort of 146 patients, the relation of these different clinical variables to the course of disease in the following 3 years was evaluated.

Results

The percentage of time with active disease in the first 2 years differed significantly between subtypes. In all subtypes, a broad spectrum of activity was observed. The time with active disease in the first 2 years was the most significant factor associated with the duration of active disease in the following years.

Conclusion

Different percentages of time with active disease have been observed between JIA subtypes in the first 2 years. The cumulative duration of activity varied widely within each subtype. Regarding the prognosis of the individual patient, the clinical course in the first 2 years appears to be predictive of the clinical course in the following years. Patients that have less time with active disease in the first 2 years are not likely to develop an unremitting clinical course later on.