Amphetamine causes dopamine depletion and cell death in the mouse olfactory bulb

Amphetamine is a neurotoxic psychostimulant that causes dopamine depletion and neuronal death in the rodent striatum. In the present study, we sought to determine if toxic doses of the drug can also induce pathological changes in the mouse olfactory bulb. We found that injections of amphetamine (10 mg/kg x 4, given 2 h apart) caused significant decreases in dopamine levels in that structure. This dose of the drug also induced substantial increases in the number of terminal deoxynucleotidyl transferase-mediated deoxyribonucleotide triphosphate (dNTP) nick end labeling (TUNEL)-positive cells in the olfactory bulb indicative of elevated DNA fragmentation. These results show that the toxic effects of amphetamine involve the olfactory bulb in addition to the striatum. These observations need to be taken into consideration when discussing the clinical course of amphetamine addiction.     

MHB4 Comparison of Standard Gamble, Time Trade-Off, and Visual Analog Scale Scores for Hypothetical Stroke Health States Using a Computer-Based Program

The most frequently used techniques for conducting utility assessments are the Standard Gamble (SG), the Time Trade-Off (TTO), and the Visual Analog Scale (VAS).
OBJECTIVES: The objectives of this study were to compare scores obtained on the SG, TTO, and VAS for hypothetical stroke health states; to determine the effect of age and gender on utility scores; to identify any ceiling or floor effects, and to determine the presence of interviewer effects.
METHODS: Forty-nine PharmD students from the College of Pharmacy at the University of Iowa were selected as the sample, and utility assessments were conducted by two interviewers, for hypothetical stroke scenarios adapted from the Glasgow Outcomes Sale. The health states evaluated were Good Recovery, Moderate Disability, Severe Disability, and a Vegetative State. Two rounds of interviews were separated by a period of 4 months. Regresion analysis was used to identify the factors influencing utility scores.
RESULTS: Mean SG scores for the four health states were 82.2, 62.7, 26.3, and 3.3, respectively. TTO scores for the four health states were 79.9, 57.3, 24.6, and 2.9, respectively. However, VAS scores were found to be higher than both TTO and SG scores. Neither age nor gender were found to be statistically significant determinants of reported utility scores. Interviewer effects were found for one out of 12 assessments in round 1, while none were observed in round 2. Floor effects were observed for all three techniques for the vegetative state.
CONCLUSION: Further research using larger, more representative samples from the general population is required to establish the validity of computer-based programs for utility assessments.     

Kidney involvement in cryoglobulinemia

The authors provide the reported data on renal impairment in mixed cryoglobulinemia (CGE) and 3 own CGE case reports. Renal impairment by the type of rapid-progressing nephritis with episodes of acute renal failure was the major sign in the clinical picture of those cases.     

Intranasal revaccination of children with live measles vaccine: development of local immunity]

Thirty-eight children aged 6-7 years were intranasally revaccinated against measles. Children without antimeasles antibodies in the serum responded to revaccination by their appearance in protective titers. In children with antibodies their titers increased (in 60%) on day 30 after intranasal revaccination. The efficacy of subcutaneous revaccination was the same. Intranasal, but not subcutaneous, revaccination resulted in appearance of nasopharyngeal anti-measles IgA. Intranasal method of revaccination against measles is convenient and safe and is recommended for clinical trials on a wide scale and for introduction into practice.     

Methamphetamine toxicity and messengers of death

Methamphetamine (METH) is an illicit psychostimulant that is widely abused in the world. Several lines of evidence suggest that chronic METH abuse leads to neurodegenerative changes in the human brain. These include damage to dopamine and serotonin axons, loss of gray matter accompanied by hypertrophy of the white matter and microgliosis in different brain areas. In the present review, we summarize data on the animal models of METH neurotoxicity which include degeneration of monoaminergic terminals and neuronal apoptosis. In addition, we discuss molecular and cellular bases of METH-induced neuropathologies. The accumulated evidence indicates that multiple events, including oxidative stress, excitotoxicity, hyperthermia, neuroinflammatory responses, mitochondrial dysfunction, and endoplasmic reticulum stress converge to mediate METH-induced terminal degeneration and neuronal apoptosis. When taken together, these findings suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity.     

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

The efficiency of combinations of Enalapril and long-acting Nifedipin and Moxonidine in patients with arterial hypertension and a metabolic syndrome

The aim of the study was to obtain a comparative evaluation of antihypertensive efficacy, tolerability and influence of combine therapy on myocardium mass, diastolic function of a left ventricle, lipid and carbohydrate exchange in patients with arterial hypertension in metabolic syndrome. Out of 40 examined cases 20 patients took enalapril and long-acting nifedipin and 20 ones--enalapril and moxonidine. All examination were been performed before administration of drugs and 6 months after the therapy. The dynamics of indices of ambulatory blood pressure monitoring, echocardiography, cycle ergometry, anthropometry, lipid, carbohydrate exchange and tolerability of conducted therapy was been evaluated. The use of this combination of the drugs may be recommended to be included in the treatment of arterial hypertension within the bounds of metabolic syndrome, as in most of cases they promote an achievement of target blood pressure level, have a cardioprotective action, high tolerability and favorable metabolic profile. The combination of enalapril and long-acting nifedipin has a more evident antihypertensive activity but a therapy with enalapril and moxonidine has a positive effect on the indices of carbohydrate exchange.     

Spectrum, incidence and prognostic value of systemic manifestations in chronic hepatitis C of low activity

AIM: To study the incidence and prognostic significance of extrahepatic manifestations of chronic HCV-infection with low activity of hepatic process and to specify treatment policy. MATERIAL AND METHODS: Sixty-two patients with low-active chronic hepatitis C (CHC) entered the study. Blood samples from all the patients were studied clinically, biochemically, immunologically and virusologically. In 58 patients the diagnosis was confirmed morphologically (liver tissue). RESULTS: Systemic manifestations of CHC were observed in 23 (37.1%) patients, in 12 of them they were associated with cryoglobulinemia. Most frequent was cryoglobulinemic vasculitis with skin (12.9%) and joint (9.7%) involvement, cryoglobulinemic glomerulonephritis (11.3%), arthralgia without association with cryoglobulinemia (11.3%). Independent risk factors for development of systemic disorders in CHC of low activity comprised female gender, age over 45, the disease duration and presence of cryoglobulinemia. CONCLUSION: CHC of low activity is characterized by high occurrence of systemic manifestations primarily associated with cryoglobulinemia. Renal affection with development of cryoglobulinemic glomerulonephritis is most prognostically significant.     

Prevalence of abnormal thyroid stimulating hormone and thyroid peroxidase antibody-positive results in a population of pregnant women in the Samara region of the Russian Federation.

Undiagnosed thyroid disease is a common problem with significant public health implications. This is especially true during pregnancy, when the health of both the mother and the developing child can be adversely affected by abnormal maternal thyroid function. Measurement of serum thyroid stimulating hormone (TSH) and thyroid peroxidase antibodies (TPO-Ab) are two common ways to assess maternal thyroid status. The objective of our study was to determine the prevalence of abnormal TSH and TPO-Ab tests in a population of pregnant women in the Samara region of the Russian Federation. Serum samples were obtained from 1588 pregnant women as part of their routine antenatal care. TSH and TPO-Ab were measured, and trimester-specific reference values for TSH (2.5-97.5 percentiles) were calculated using TPO-Ab-negative women. TSH results outside these ranges were considered abnormal; TPO-Ab levels outside the manufacturer's reference range (>12 IU/mL) were considered abnormal. Overall, the prevalence of abnormal results was 6.3% for TSH and 10.7% for TPO-Ab. High TSH (>97.5 trimester-specific percentile) and TPO-Ab-positive results were most common in the first trimester (5.7% and 13.8%, respectively). TSH levels were associated with gestational age and TPO-Ab status, and with maternal age in TPO-Ab-negative women. TPO-Ab status was associated with both maternal and gestational age. Women with TSH >2.5 mIU/L had a significantly increased risk of being TPO-Ab-positive, and this risk increased with age. Based on our data, we conclude that abnormal TSH and TPO-Ab are common in pregnant women of the Samara region. Given the association of thyroid dysfunction to adverse pregnancy outcomes, screening of this population for abnormal thyroid function should be considered.