Ontogeny of the striatal neurons expressing the D1 dopamine receptor in humans

We studied D1 dopamine receptor (D1R) gene expression in the human striatum during ontogeny by in situ hybridization, immunohistochemistry, and D1R ligand autoradiography. D1R mRNA, protein, and binding sites ([³H]SCH 23390) were detected in the striatum from week 12 of fetal life. At this time, D1R mRNA was predominant in the striosomal neurons; D1R immunoreactivity (D1R-IR) and D1R binding sites displayed a pattern similar to D1R mRNA. D1R-IR was essentially present in striosomal cell bodies and neuropil, whereas only a few cell bodies were detected in the matrix. From week 20 of fetal life, D1R gene expression developed in the matrix neurons as well, thus leading to an even D1R mRNA expression throughout striosomes and matrix compartments at birth. Comparative analysis of the expression of D1R and dynorphin mRNA show the same developmental patchy pattern up to week 26. Indeed, neurons expressing the D1R gene contain dynorphin mRNA; in contrast, they do not express the preproenkephalin A gene. At birth, the pattern of D1R mRNA expression level was sharply different from that of dynorphin (DYN) gene expression. High DYN mRNA expression was restricted to the striosomes, whereas high D1R mRNA expression was present in the whole striatum. These results demonstrate that, during human ontogeny, functional D1 receptors are expressed as early as week 12 in the striatum, developing initially in the striosomal neurons containing high dynorphin mRNA content. Toward the end of fetal life, there is a dissociation between D1R and DYN expression levels, suggesting that neuroanatomical or neurochemical modifications occur at this period, which may contribute to the regulation of the tone of the striatal D1R and DYN gene with topological specificity. © 1996 Wiley-Liss, Inc.     

Piper umbellatum L.: A comparative cross-cultural analysis of its medicinal uses and an ethnopharmacological evaluation

Aim of the study

This review assesses the botany, traditional medicinal uses, phytochemistry, pharmacology and toxicology of P. umbellatum.

Materials and methods

Information on P. umbellatum was gathered via the internet (using Scirus, Google Scholar, CAB-Abstracts, MedlinePlus, Embase, Scielo, and Web of Science) and libraries. Additionally, previously unpublished work on the traditional uses of P. umbellatum from our National Study of the Medicinal Plants of the Dominican Republic has been included.

Results

Piper umbellatum is a Neotropical plant species widely distributed in Mexico, Central America, South America and the West Indian Islands. It has also been introduced to Africa and South-East Asia. Traditional uses for this plant are recorded in 24 countries in three continents, America, Africa and Asia for a wide range of ailments such as kidney, women diseases, diarrhea, skin affections, burns, rheumatism, malaria, intestinal parasites, inflammation and fever. We have analyzed the cross-cultural agreement among traditional uses in different countries and found a high degree of consensus for the indications kidney/diuretic, stomachache and wounds. Phytochemical studies of P. umbellatum have demonstrated the presence of terpenes (mainly found in the essential oil), alkaloids, flavonoids, sterols and other classes of secondary metabolites. The extracts and pure compounds derived from P. umbellatum show a wide spectrum of pharmacological activities including antibacterial, anti-inflammatory, analgesic, antioxidant, cytotoxic, antimalarial, antileishmanial, and antitrypanosomal activity. A first commercial product is in development, based on the plant's protective characteristics against UV irradiation.

Conclusions

The interesting biological activities of P. umbellatum need further research in in vivo experiments and clinical studies. The outcome of these investigations will determine the possible development of drugs from P. umbellatum.     

Elevated levels of small,low‐density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: Possible contribution of phospholipase A2 to this atherogenic profile

Objective

This work studied the presence of inflammatory and atherogenic lipoprotein markers that could explain the high incidence of cardiovascular disease (CVD) reported in rheumatoid arthritis (RA) patients.

Methods

Inflammatory markers were 1) soluble adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C‐reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon‐γ [IFNγ], tumor necrosis factor α [TNFα]), and 5) secretory group IIA phospholipase A₂(sPLA₂‐IIA). Atherogenic lipoprotein markers were 1) the size distribution of plasma lipoprotein subclasses, and 2) the binding affinity of low‐density lipoprotein (LDL) to chondroitin 6‐sulfate glycosaminoglycan (GAG).

Results

RA patients (n = 31) and matched controls (n = 28) had similar plasma concentrations of total cholesterol, triglycerides, Apo B, Apo A‐I, very low‐density lipoprotein, intermediate‐density lipoprotein, and high‐density lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA₂‐IIA, ICAM, CRP, Fb, TNFα, and IFNγ compared with controls. RA patients also had significantly higher levels of small, dense LDL‐1 (P < 0.05) and lower levels of small HDL‐2 particles (P < 0.001) compared with controls. In addition, LDL from RA patients had a significantly higher binding affinity (K_d) to GAG (mean ± SD K_d 204 ± 22.4 nM Apo B) than did LDL from control subjects (K_d 312 ± 36 nM Apo B) (P < 0.05). This K_d value showed a significant negative correlation with the plasma levels of LDL‐1 (r = −0.566, P ≤ 0.004). In RA patients, a significant positive correlation was obtained between sPLA₂‐IIA and CRP, ICAM, and LDL‐1. HDL‐2 showed a negative correlation with sPLA₂‐IIA.

Conclusion

These atherogenic lipoprotein factors combined with the presence of chronic inflammation may contribute to the high CVD‐related mortality in RA patients.

     

New chromosomal alterations in a series of 23 splenic marginal zone lymphoma patients revealed by Spectral Karyotyping (SKY)

Splenic marginal zone lymphoma (SMZL) is a B-cell lymphoproliferative disorder with characteristic clinical, immunophenotypic, cytological and histological features. Some karyotypic abnormalities have been related to this disorder and most of them are usually complex and difficult to define. The aim of present study was to characterize new chromosomal aberrations involved in this disease. We performed conventional banding cytogenetics and Spectral Karyotyping (SKY) technique in 23 patients diagnosed with SMZL having a complex karyotype among a series of 160 SMZL cases. Del(7)(q22-q32) and trisomy 3/3q were the most common chromosomal aberrations. In addition, new translocations involving chromosomes 3, 6, 8, 9, 12 and 14q32 region were detected.     

Histologic and Histomorphometric Evaluation of a New Bioactive Liquid BBL on Implant Surface: A Preclinical Study in Foxhound Dogs

Background: Bioactive chemical surface modifications improve the wettability and osseointegration properties of titanium implants in both animals and humans. The objective of this animal study was to investigate and compare the bioreactivity characteristics of titanium implants (BLT) pre-treated with a novel bone bioactive liquid (BBL) and the commercially available BLT-SLA active. Methods: Forty BLT-SLA titanium implants were placed in in four foxhound dogs. Animals were divided into two groups (n = 20): test (BLT-SLA pre-treated with BBL) and control (BLT-SLA active) implants. The implants were inserted in the post extraction sockets. After 8 and 12 weeks, the animals were sacrificed, and mandibles were extracted, containing the implants and the surrounding soft and hard tissues. Bone-to-implant contact (BIC), inter-thread bone area percentage (ITBA), soft tissue, and crestal bone loss were evaluated by histology and histomorphometry. Results: All animals were healthy with no implant loss or inflammation symptoms. All implants were clinically and histologically osseo-integrated. Relative to control groups, test implants demonstrated a significant 1.5- and 1.7-fold increase in BIC and ITBA values, respectively, at both assessment intervals. Crestal bone loss was also significantly reduced in the test group, as compared with controls, at week 8 in both the buccal crests (0.47 ± 0.32 vs 0.98 ± 0.51 mm, p < 0.05) and lingual crests (0.39* ± 0.3 vs. 0.89 ± 0.41 mm, p < 0.05). At week 12, a pronounced crestal bone loss improvement was observed in the test group (buccal, 0.41 ± 0.29 mm and lingual, 0.54 ± 0.23 mm). Tissue thickness showed comparable values at both the buccal and lingual regions and was significantly improved in the studied groups (0.82–0.92 mm vs. 33–48 mm in the control group). Conclusions: Relative to the commercially available BLT-SLA active implants, BLT-SLA pre-treated with BBL showed improved histological and histomorphometric characteristics indicating a reduced titanium surface roughness and improved wettability, promoting healing and soft and hard tissue regeneration at the implant site.     

Dobutamine Stress Echocardiography and Exercise Electrocardiography for Risk Stratification in Medically Treated Unstable Angina

Previous reports have demonstrated the superiority of exercise echocardiography over exercise electro-cardiography (ex-ECG) for risk stratification in patients with medically stabilized unstable angina (UA). We sought to analyze the prognostic value of dobutamine stress echocardiography (DSE) compared with ex-ECG for risk stratification in patients with UA. METHODS: Ninety-two patients with medically treated UA were studied (mean age 65 +/- 11 years, 24 women, 42% of patients had electrocardiographic abnormalities on admission). Dobutamine stress echocardiography and treadmill ex-ECG were performed on the third day after hospital admission. End points were recurrent UA, myocardial infarction (MI), or cardiac death. RESULTS: Mean follow-up was 24 +/- 7 months. During follow-up, 22 patients had cardiac events (18 recurrent UA, 2 MI, 2 cardiac deaths). The event-free survival rate was 80% for patients with negative DSE results for ischemia and 52% for those with positive DSE results (log rank 9.57; P =.002), compared with an event-free survival rate of 79% for patients with negative ex-ECG results and 66% for those with positive ex-ECG results (log rank 2.06; P = not significant). Left ventricular dysfunction (P =.01) and a positive dobutamine stress echocardiogram (P =.03), but not a positive exercise electrocardiogram, were independent predictors of cardiac events during follow-up. CONCLUSIONS: Dobutamine stress echocardiography performed early in medically treated patients with UA predicts cardiac events during follow-up more accurately and with more specificity than ex-ECG does in this population.