Dopamine D2 Modulation of Sign and Goal Tracking in Rats

In Pavlovian conditioning, sign- and goal-tracking behaviors represent different approaches towards the conditioned stimulus. These behavioral patterns have been associated with predictive or incentive properties of the conditioned stimulus, with a crucial involvement of the mesolimbic dopamine system. As it is possible that sign tracking behavior is more sensitive to dopamine modulation, we evaluated the dopamine-dependence of sign- and goal-tracking behavior. We assessed responses to both a D2 agonist and an antagonist, and tested performance in a behavioral paradigm known to activate dopamine projections and in an animal model that affects mesolimbic and mesocortical function. Sign trackers displayed a greater sensitivity to a D2 agonist and smaller prepulse inhibition of the acoustic startle response than goal trackers, suggesting a reduced inhibitory ability. In addition, a neonatal ventral hippocampal lesion resulted in the loss of incentive salience of cues in sign trackers. Overall, these data indicate that sign-tracking behavior is more heavily controlled by dopamine than goal tracking.     

Effect of different doses of hexavalent chromium on mandibular growth and tooth eruption in juvenile Wistar rats

Not only workers employed at industrial plants are exposed to intoxication with the element they manipulate, the population at large is also at risk of suffering health problems caused by contaminating wastes inadequately treated for their safe disposal. As a result certain toxic substances, such as hexavalent chromium,has reached the general population including children. The present study sought to evaluate the effect of intoxication with hexavalent chromium on body and mandibular growth and tooth eruption in suckling Wistar rats. Potassium dichromate was administered by gavage in a dose of 6.25 or 12.5 mg/kg body weight (b.w.) to one of the two groups of 4-day-old Wistar rats during 10 days. Our results showed that the effects of chromium are dose-dependent. Morphometric studies of body growth showed lower body weight in both experimental groups and shorter tail length in animals receiving 12.5 mg/kg b.w. dose of chromium, compared with controls. All parameters of mandibular growth were lower in the experimental group receiving 12.5 mg/kg b.w. of chromium. Differences in tooth eruption were observed at the level of the first molar in animals receiving 12.5 mg/kg and of the second molar in those receiving 6.25 mg/kg b.w. of chromium. Chromium was found to affect all the studied parameters.     

Chagas disease in rural areas of Chaco Province, Argentina: epidemiologic survey in humans, reservoirs, and vectors

We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population along with domiciliary infestation by triatomine bugs in an area endemic for Chagas disease in the Chaco Province of Argentina. In addition, we carried out parasitologic surveys in patients, dogs, wild mammals, and vectors. The mean seroprevalence in humans was 27.81% (109 of 392) and 24.14% (63 of 261) in 1-15-year-old children. The minimum domiciliary infestation rate was 13.33%, with certain areas reaching 53.85%. The prevalence was 15.09% (16 of 106) in dogs and 35.71% (10 of 28) in opossums. Infection with T. cruzi was detected in 30.10% (59 of 196) of the Triatoma infestans tested. Compared with nationwide studies, our data suggest that 1) there are zones requiring immediate sanitary action, and 2) nationwide estimates are based on very heterogeneous epidemiologic situations. This heterogeneity emphasizes the importance of in-depth studies of restricted areas to provide additional information for a better understanding of the present status of Chagas disease in Argentina.     

Outcomes and cost of deep venous thrombosis among patients with cancer

BACKGROUND: Although deep venous thrombosis (DVT) often complicates the clinical course in patients with cancer, few studies of the outcomes of DVT in this population have been published. Furthermore, the cost of DVT is largely undescribed. We herein report the largest study of DVT in this population to date. METHODS: We reviewed the medical records of 529 consecutive cancer patients in whom DVT developed from January 1, 1994, through December 31, 1997, and followed up these patients through December 31, 2000, for outcomes. The cost of hospitalization was obtained from our hospital's cost-accounting system and inflated to 2002 US dollars using the Consumer Price Index for Medical Care. Logistic regression was used to identify factors that were associated with a high risk of poor outcomes. RESULTS: The most common complication of DVT was bleeding, which occurred in 13% of patients. Pulmonary embolus occurred in 4%. Five patients (1%) died of complications of DVT and 5 (1%) of complications of anticoagulation. Recurrence of DVT was common (17% overall), particularly among those who had inferior vena cava filters (32%; P<.001) or a previous episode of DVT (P =.03). All but 4 patients were hospitalized for initial anticoagulation therapy, for a mean of 11 days. The mean cost of hospitalization was 2002 US $20 065. CONCLUSIONS: Among patients with cancer, DVT frequently is associated with serious clinical outcomes. Its treatment is resource intensive and costly. More effective agents and less costly management strategies could have a significant impact on the outcomes and cost of DVT in this population.     

Cover Image,Volume 20, Issue 4

The cover image, by Inmaculada Ruz‐Maldonado et al., is based on the Original Article LH‐21 and abnormal cannabidiol improve β‐cell function in isolated human and mouse islets through GPR55‐dependent and ‐independent signalling, DOI: 10.1111/dom.13180 .

     

Use of calcium hydroxylapatite (Radiesse?) for facial augmentation

Radiesse^® (Bioform Inc, USA) is a sterile, latex-free, non-pyrogenic, semi-solid, cohesive subdermal, injectable implant, whose principal component is synthetic calcium hydroxylapatite, a biocompatible material with over 20 years of use in medicine. The semi-solid nature of the product is created by suspending calcium hydroxylapatite microspheres of 25–45 microns diameter in a gel carrier of carboxymethylcellulose. The product has FDA approval for esthetic facial augmentation in the US. Such approval includes the long-lasting correction of moderate to severe facial wrinkles and folds and the treatment of facial fat loss due to immunodeficiency virus infection. Diverse facial regions can be injected in order to ameliorate or enhance some features: glabellar lines, subdermal support of the brows, malar and buccal fat pads, tear troughs, nasolabial folds, nose, lips, perioral region, marionette lines, oral commisures and chin among others, as well as saucerized acne scars. Other medical indications include nipple projection for nipple areolar reconstruction, urinary incontinence, vesicoureteral reflux, vocal cord augmentation, and use as a radiographic tissue marker. The average lasting result is from 12 to 18 months. Radiesse can be considered an effective soft-tissue filler for overall longevity, biocompatibility, and low rate of side effects.     

Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis

Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p‐values (p < 1 × 10^?4). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (β ± SE = ?0.25 ± 0.05, p = 6.23 × 10^?6). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p‐value < 1 × 10^?4). The best association was observed on chromosome 9 with rs59902911 (β ± SE = 0.86 ± 0.17, p = 1.01 × 10^?6), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.     

Genotypic characterization of drug-resistant Mycobacterium tuberculosis isolates from Peru.

SETTING: Twenty-nine epidemiological unrelated and mostly multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains from Peruvian patients. OBJECTIVE: To investigate the molecular genetics of MDR-TB strains recovered in a Latin American country. DESIGN: Antimicrobial agent susceptibility testing, major genetic group designation, IS6110 fingerprinting, spoligotyping, and automated deoxyribonucleic acid sequencing of regions of the katG, rpoB, embB, gyrA, and pncA genes with mutations commonly associated with drug resistance. RESULTS: Nineteen isolates were found to be multidrug-resistant by susceptibility testing. IS6110 typing showed that virtually all isolates were unique and therefore had independently acquired drug resistance. Seventy-nine percent of isoniazid-resistant strains had a Ser315Thr amino acid change in KatG. Ninety-five percent of rifampin-resistant isolates had amino acid replacements in the rifampin-resistance determining region of RpoB. Six of 11 ethambutol-resistant strains had EmbB alterations. Eleven pyrazinamide-resistant strains had distinct mutations in pncA. CONCLUSION: Virtually all organisms evolved drug resistance independently. The types of drug resistance-associated mutations identified were very similar to changes occurring in isolates from other areas of the world. Nucleotide sequence-based strategies for rapid detection of drug resistance-conferring mutants will be applicable to organisms recovered in Peru, and potentially other areas of Latin America.     

Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA.

The effectiveness of the chelating agent CaNa2EDTA and the peptidomimetic matrix metalloproteinase inhibitor batimastat (BB-94) to inhibit local tissue damage induced by Bothrops asper snake venom was studied in mice. Both compounds totally inhibited proteolytic, hemorrhagic, and dermonecrotic effects, and partially reduced edema-forming activity, when incubated with venom prior to injection. Much lower concentrations of batimastat than of CaNa2EDTA were required to inhibit these effects. In addition, batimastat, but not CaNa2EDTA, partially reduced myotoxic activity of the venom. When the inhibitors were administered at various time intervals after envenomation at the same site of venom injection, both compounds were effective in neutralizing local hemorrhage and dermonecrosis if administered rapidly after venom. Inhibition was not as effective as the time lapse between venom and inhibitor injections increased. Owing to the relevance of metalloproteinases in the pathogenesis of local tissue damage induced by B. asper and other pit viper venoms, it is suggested that administration of peptidomimetic metalloproteinase inhibitors or CaNa2EDTA at the site of venom injection may represent a useful alternative to complement antivenoms in the neutralization of venom-induced local tissue damage.