Effects of some antiepileptic and proconvulsant drugs on kainic acid-induced limbic epilepsy in cats

The effects of parenteral administration of diazepam (3 mg/kg), DL-C-allylglycine (60–80 mg/kg), and ketamine (20 mg/kg) on kainic acid (KA)-induced limbic seizures were investigated in cats. Single microinjections of KA (1–4 μg) into the amygdaloid complex were followed by local sustained paroxysmal discharges in the limbic system. Seizures consisted of tonic clonic EEG discharges accompanied by orienting reaction to the ipsilateral side of injection and masticatory movements, facial jerks, and aggressive behaviour. Ictal discharges occurred every 5–10 min during the first hours after KA injection and then progressively disappeared within 1 wk. Interictal discharges remained for longer periods, but after 3 or 4 wk they were abolished. Diazepam completely blocked limbic seizures but not high-frequency discharges in the site of injection and the ipsilateral hippocampus. The animals were protected for 30 to 60 min. At the same time, diazepam decreased multiple-unit activity in the pontine reticular formation and the lateral geniculate nucleus and produced a general hypotonia state. DL-C-allylglycine activated KA amygdaloid focus during the remission state and ketamine produced independent epileptiformlike activity which interfered with that produced by KA injection.     

The genetic immunization with paraflagellar rod protein-2 fused to the HSP70 confers protection against late Trypanosoma cruzi infection

The immunological properties of the Trypanosoma cruzi paraflagellar rod proteins (PFR2 and PFR3) administered alone as well as fused to HSP70 have been analyzed in mice in the context of genetic immunization. The immunization of mice with the DNA vectors containing the PFRs gene or PFRs-HSP70 fused genes induced high level of IgG(2a) anti-PFRs. However, only the immunization with the PFR2-HSP70 fused genes triggers in spleen cells a statistically significant enhancement of expression of IL-12 and IFN-gamma and a decrease in the percentage of cells expressing IL-4. Likewise, the PFR2-HSP70 molecule elicits a statistically significant activation of PFR2 antigen specific CTLs. Immunization with the PFR2-HSP70 chimeric gene provided a protective response against a T. cruzi experimental infection.     

Increased frequency of disease-causing MYH mutations in colon cancer families

The genetic factors that cause clustering of colorectal cancers (CRCs) other than mutations in the mismatch repair (MMR) genes are not well understood. Clustering in families who lack MMR gene mutations may be attributable to low-penetrance mutations. Hypothetically, mono-allelic MYH mutations could contribute to the risk of CRC in these families. Using Fisher's exact test and logistic regression, we compared the frequency of the known disease-causing MYH mutations Y165C, G382D and 466delE in 137 probands (117 cases with CRC and 20 cases diagnosed on the basis of adenomatous polyps only) from families with three or more CRCs but negative for mutations in the MMR genes and in 967 healthy controls with comparable ethnic backgrounds. Of 137 cases, 6 (4.4%) carried mono-allelic MYH mutations compared with 16 of 967 (1.6%) controls. In addition, three bi-allelic MYH mutation carriers, who eventually developed MYH-associated polyposis, were also identified in families with pedigree structures consistent with dominant inheritance of CRC susceptibility. By Fisher's exact tests, there was a statistically different frequency of cases with any MYH mutation (mono- or bi-allelic carriers; P-value = 0.002) and of cases with mono-allelic MYH mutation (P = 0.04) compared with the controls. Using a logistic regression model, the unadjusted odds ratio associated with any MYH mutation was 4.14 (P-value < 0.001); for mono-allelic carriers, it was 2.79 (P-value = 0.04). Adjusting for ethnic backgrounds, gender and age, the odds ratio associated with any disease-causing MYH mutation was 3.23 (P-value = 0.01); for mono-allelic carriers, it was 1.99 (P-value = 0.20). Overall, the results support previous studies suggesting that mono-allelic mutations of MYH constitute low-penetrance CRC-causing alleles. These data further support a model in which low-penetrance alleles are enriched in MMR gene mutation-negative CRC families.     

Coronary Heart Disease and Dyslipidemia: A Cross-Sectional Evaluation of Prevalence, Current Treatment, and Clinical Control in a Large Cohort of Spanish High-Risk Patients: The PRINCEPS Study

The authors assessed a large cohort of patients with coronary heart disease (CHD) or at high risk for developing CHD in terms of lipid profile, lipid-lowering treatment, and attainment of National Cholesterol Education Program (NCEP) target low-density lipoprotein cholesterol (LDL-C) levels. The investigation was a cross-sectional study involving Spanish outpatients treated in primary or secondary care facilities. From a total of 26,598 attending patients, 12,128 with CHD or CHD risk equivalents were recruited by 1875 physicians; 49% had CHD and 69% had multiple risk factors. Only 25% of patients attained LDL-C values <100 mg/dL, 76.6% patients received lipid-lowering therapy (statins in 95.4% of cases), and 54% of physicians considered that a treatment change was required (the most frequent choice was the addition of ezetimibe to current statin therapy). In this large cohort of high-risk coronary patients, only 25% attained a target LDL-C of <100 mg/dL. These results highlight a need for improved patient care and physician awareness/training.     

Therapeutic 188Re‐lanreotide: determination of radiopharmacokinetic parameters in rats

Objectives The radiopharmacokinetic parameters of the therapeutic radiopharmaceutical ¹⁸⁸Re‐lanreotide were compared in rats implanted with hepatocarcinoma tumours (n= 18) and healthy rats (n= 18). Methods Rats were injected with approximately 1.8 MBq ¹⁸⁸Re‐lanreotide (0.1 ml) via the tail vein and blood samples were obtained. The activity per gram of tissue (%IA/g) was calculated and the radiopharmacokinetic parameters determined. Data were fitted using a two‐compartment model. Key findings Significant differences were found between healthy and hepatoma rats for beta elimination half‐life (22.56 vs 48.14 h); transference constants K₁₀ (k_e) (6.44 vs 3.05 h^‐1) and K₁₂ (2.76 vs 7.09 h^‐1); volume of distribution (2.06 vs 5.45 ml); mean residence time (66.58 vs 95.50 h) and apparent volume of distribution at steady state (131.30 vs 810.37 ml). The tumour/organ ratios after 24 h were 11.20 for tumour/muscle, 8.00 for tumour/liver and 7.72 for tumour/bone. The scintigraphic images obtained therefore had high resolution. Conclusions ¹⁸⁸Re‐lanreotide had a prolonged beta elimination half‐life and increased volume of distribution in rats with hepatocellular carcinoma. This may be beneficial in the diagnosis and therapy of metastatic lesions in patients with cancer.     

Central role of supporting cells in cochlear homeostasis and pathology

HYPOTHESIS: Supporting cells have a crucial role in degenerative and regenerative events of primary sensorial hair cells of the organ of Corti. This new role should determine future studies about pathophysiology of hearing loss and its regenerative treatment. SUPPORTING EVIDENCE: Recent findings suggest an active role of supporting cells in the maintenance of hair cell function and structure. Evidences of high energy consumption and close proximity to auditory nervous fibers suggesting K+ active exchange, preferential expression of specific proteins and antigens, presence of glucocorticoids receptors, affinity for cisplatin and regenerative potential give the supporting cells an important role in homeostasis of the organ of Corti and in some specific diseases affecting this structure. CONCLUSION: As well as glial cells provide protection and regeneration to neural tissues, supporting cells may provide the necessary metabolic and electrolitic conditions for hair cells mechanical and bioelectrical function. This opens new possibilities for the treatment of apparently "irreversible" destruction of the inner ear.     

A nationwide analysis of US racial/ethnic disparities in smoking behaviors, smoking cessation, and cessation-related factors

Objectives. We used nationally representative data to examine racial/ethnic disparities in smoking behaviors, smoking cessation, and factors associated with cessation among US adults.Methods. We analyzed data on adults aged 20 to 64 years from the 2003 Tobacco Use Supplement to the Current Population Survey, and we examined associations by fitting adjusted logistic regression models to the data.Results. Compared with non-Hispanic Whites, smaller proportions of African Americans, Asian Americans/Pacific Islanders, and Hispanics/Latinos had ever smoked. Significantly fewer African Americans reported long-term quitting. Racial/ethnic minorities were more likely to be light and intermittent smokers and less likely to smoke within 30 minutes of waking. Adjusted models revealed that racial/ethnic minorities were not less likely to receive advice from health professionals to quit smoking, but they were less likely to use nicotine replacement therapy.Conclusions. Specific needs and ideal program focuses for cessation may vary across racial/ethnic groups, such that approaches tailored by race/ethnicity might be optimal. Traditional conceptualizations of cigarette addiction and the quitting process may need to be revised for racial/ethnic minority smokers.Racial/ethnic minorities in the United States experience a disproportionate burden of smoking-related diseases, including cancer and heart disease, despite having larger proportions of light and intermittent smokers and generally lower adult smoking prevalence rates than non-Hispanic Whites.^1–3 Racial/ethnic minorities are also less likely to quit smoking successfully than are non-Hispanic Whites.^4–8 For example, rates of successful smoking cessation among African American smokers are lower than they are among non-Hispanic Whites, despite reports citing lower cigarette consumption.^2,5,7,9 Similarly, Hispanics/Latinos do not experience higher rates of successful quitting than non-Hispanic Whites, despite being more likely to be light and intermittent smokers.^2,9 There is currently no evidence indicating that Asian Americans quit at higher rates than non-Hispanic Whites in the United States.¹⁰ The examination of racial/ethnic disparities in smoking behaviors, successful quitting, and factors associated with quitting can provide valuable information for focusing strategies for groups currently experiencing lower rates of successful smoking cessation, and can lead to decreases in smoking-related disease rates across all racial/ethnic populations.Previous research on population-level data has found several factors to be associated with successful smoking cessation. For example, banning smoking in one''s home can greatly increase the chances of successfully quitting smoking. The presence of a complete ban on smoking in one''s home is associated with being quit for at least 90 days¹¹ and with being a former smoker.¹² However, an analysis of national data found that smaller percentages of non-Hispanic Whites (64.0%) and African Americans (64.4%) have a complete home smoking ban than do Hispanics/Latinos (78.0%) and Asian Americans/Pacific Islanders (79.2%).¹³ Being advised to quit smoking by health care professionals, especially physicians, has also been associated with increased rates of smoking cessation.^14–17 Despite progress in smokers being advised to quit by health care practitioners in the past 5 years, African American and Hispanic/Latino smokers remain less likely than non-Hispanic Whites to be advised to quit.^16,18 Finally, although evidence of the effectiveness of nicotine replacement therapy (NRT) at the population level has been challenged recently,^19,20 there is evidence that NRT can aid successful cessation.^17,21–23 There is substantial evidence that racial/ethnic minorities are less likely to be prescribed NRT^14,15,18 and to use NRT to quit smoking.^23–25The Tobacco Use Supplements to the Current Population Surveys (TUS-CPS) have provided invaluable data for the examination of various smoking-related issues at the national level.^11,13 In 2003, the TUS-CPS included a special supplement that focused heavily on smoking cessation. This supplement was the first TUS-CPS with this focus (and is the only one to date), and it provides arguably the richest representative national-level data on smoking cessation in the United States. This special supplement thus presented a unique opportunity to examine in detail the disparities between racial/ethnic groups in smoking cessation and important related factors.For our study, we hypothesized the following: (1) African Americans would experience less success in quitting smoking than would non-Hispanic Whites, (2) Asian Americans/Pacific Islanders and Hispanics/Latinos would be more likely to have a complete home smoking ban than would non-Hispanic Whites, (3) African Americans and Hispanics/Latinos would be less likely than would non-Hispanic Whites to report being advised by a health professional to quit smoking, and (4) racial/ethnic minorities would be less likely to use NRT than would non-Hispanic Whites.To examine these hypotheses, we conducted a secondary data analysis of the 2003 TUS-CPS to assess smoking cessation rates and examine how factors associated with successful smoking cessation differed across racial/ethnic groups among adults in the United States. Findings from this report may provide insight into optimal design of targeted smoking cessation interventions for members of specific racial/ethnic groups.