Anxiolytic-like effect of neuropeptide Y (NPY) and NPY13–36 microinjected into vicinity of locus coeruleus in rats

Neuropeptide Y (NPY, 1 and 10 pmol), NPY Y₁ receptor agonist [Leu³¹,Pro³⁴]NPY (10 pmol) and Y₂ agonist NPY_13–36 (100 pmol) were administered unilaterally into the region of the nucleus locus coeruleus (LC) in rats. NPY (10 pmol) and NPY_13–36 increased the percentage of open arm entries, the percentage of time spent on open part, number of both open and closed arm entries and line crossings in the open part while [Leu³¹,Pro³⁴]NPY failed to modify elevated plus-maze behavior. These data suggest that NPY applied close to LC has anxiolytic-like effects by acting on NPY Y₂, not on Y₁ receptors. Thus, NPY Y₂ receptors in the vicinity of LC may be involved in the regulation of anxiety in rats.     

Prescribing patterns of optometrists newly licensed in therapeutic drug use in New York State.

PURPOSE: As part of the New York State law authorizing optometrists to use Therapeutic Pharmaceutical Agents (TPAs), the New York State Education Department commissioned a study to monitor and assess the prescribing patterns and competence of optometrists newly licensed to use TPAs. This report summarizes the findings of that study. METHODS: The database was obtained from more than 11,000 Patient Data Reporting Forms (PDRFs) returned by 535 optometrists, listing diagnosis, type(s) of medication(s) prescribed, treatment outcome, and possible adverse effects. RESULTS: Of the more than 11,000 forms returned by 535 optometrists, 8,936 were first visits, with 5,828 follow-up visits scheduled. For all reported initial visits, only 89 patients required ophthalmological referral for secondary or tertiary care. No adverse drug reactions requiring intervention were reported. The most-frequent diagnoses treated by optometrists were related to allergies, superficial trauma, conjunctivitis (unspecified), and then blepharitis. The most commonly prescribed ophthalmic preparations as actually reported on the PDRFs were Polytrim (trimethoprim/ polymixin B), tobramycin (brand name and generic), TobraDex (tobramycin/dexamethasone), and Livostin (levocabastine). CONCLUSIONS: When analyzed according to diagnosis, the data indicate that the prescribing patterns of the prescribing optometrists adhered to currently accepted clinical guidelines. Based on the available data and the lack of observed side effects, the use of topical medications to treat anterior-segment disease by optometrists in New York State appears to be safe, and should be of benefit to patients who seek care from optometrists.     

Analysis of the role of cyclic adenosine 3′,5′-monophosphate in catecholamine release

1. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels and catecholamine release were measured in cat adrenal glands perfused in situ with Locke solution.2. Cyclic AMP was present in the medulla in an amount which represented approximately one fifth of that present in the cortex.3. Perfusion with acetylcholine (ACh) or nicotine increased cyclic AMP both in the intact adrenal and in the perfusate. The time course of the changes in tissue cyclic AMP during stimulation was out of phase with the time course of catecholamine release. Maximal increases in cyclic AMP were not manifest until after 8 min of exposure to the secretogogue, whereas maximal rates of secretion occurred during the first minute.4. Theophylline (0.5 mM) increased basal and stimulated adrenal cyclic AMP levels, but did not potentiate the secretory response to ACh or nicotine.5. Perfusion with cyclic AMP or its dibutyryl derivative (0.2-4 mM) failed to effect a consistent or significant increase in the rate of catecholamine release and was unable to potentiate the secretory response to a submaximal concentration of ACh or calcium.6. The results suggest that, unlike calcium, cyclic AMP is not a direct mediator of medullary secretion.     

Echocardiographic assessment of the different left ventricular geometric patterns in middle-aged men and women in Tallinn

The aim of this study was to determine the association of left ventricular (LV) geometry with sex, age, arterial hypertension and obesity in Tallinn. In a framework of a population study for cardiovascular risk factors, echocardiography was carried out in 325 men and 398 women (69.3% of all 1043 participants aged 35-59) in 1999-2001. Left ventricular hypertrophy was defined if left ventricular mass (LVM), LVM/height and LVM/body surface area were 294 g, 163 g/m and 150 g/m2 in men, and 198 g, 121 g/m and 120 g/m2 in women, respectively. LV geometry was analysed according to four types generally recognized (with regard to relative wall thickness > 0.45). The prevalence of concentric hypertrophy was similar in men and women: 7.7% and 9.1%. The prevalence of eccentric hypertrophy was significantly higher in women than in men (33.3% vs 4.9%). Concentric remodelling was also found in women more often than in men (9.5 vs 5.5%; p < 0.05). Regardless of sex and age, concentric hypertrophy was never found in participants with blood pressure < 140/90. In hypertensives, there was a tendency for age-related increase of concentric hypertrophy prevalence: the latter was higher in women than in men: 39.1% vs 25.5%; p < 0.05. In examinees with BMI < 30, this type of LV geometry was seldom found: in 3.1% of men and 5.0% of women; p < 0.05. In obese persons, it increased with age, reaching 26.5% in men and 21.2% in women (p < 0.05). The prevalence of eccentric hypertrophy in men increased with age, and with hypertension and obesity. The prevalence of concentric remodelling in men was not related to BMI; it was significantly more often found in older age groups and in hypertensives. In women, the prevalence of eccentric hypertrophy and concentric remodelling was not related to age, hypertension or obesity.     

An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity

Type I IFNs were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of IFN antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of IFN-induced antiviral activity. Here, we identify a role for RNase-L in the host antibacterial response. RNase-L^−/− mice exhibited a dramatic increase in mortality after challenge with Bacillus anthracis and Escherichia coli; this increased susceptibility was due to a compromised immune response resulting in increased bacterial load. Investigation of the mechanisms of RNase-L antibacterial activity indicated that RNase-L is required for the optimal induction of proinflammatory cytokines that play essential roles in host defense from bacterial pathogens. RNase-L also regulated the expression of the endolysosomal protease, cathepsin-E, and endosome-associated activities, that function to eliminate internalized bacteria and may contribute to RNase-L antimicrobial action. Our results reveal a unique role for RNase-L in the antibacterial response that is mediated through multiple mechanisms. As a regulator of fundamental components of the innate immune response, RNase-L represents a viable therapeutic target to augment host defense against diverse microbial pathogens.     

High prevalence of coeliac disease: Need for increasing awareness among physicians

BACKGROUND: Coeliac disease is a wheat gluten and related prolamines-induced disease with a prevalence that may be underestimated in many geographical regions and populations. AIM: To investigate the prevalence of coeliac disease in a population of schoolchildren of Estonia using tissue transglutaminase antibodies for screening. SUBJECTS AND METHODS: The study was designed as cross-sectional. Serum samples from 1160 randomly selected schoolchildren (636 female and 564 male, aged 9 or 15 years) were studied using a novel tissue transglutaminase antibody immunoassay (EliA Celikey IgA assay). Antibody-positive subjects were investigated for coeliac disease. RESULTS: A total of five subjects had antibodies. Four of them agreed for further investigations. By small-bowel biopsy they all were confirmed to have active coeliac disease, including three subjects with symptoms that were not considered by their family doctors. The prevalence of coeliac disease is at least 1 case per 290 (0.34% with CI 0.09-0.88%) in Estonia. It is much higher than that in our previous screening studies but is comparable with data from other European countries. CONCLUSION: The prevalence of coeliac disease might have increased during the last decade in Estonia. This study clearly shows that the awareness of coeliac disease among physicians is low. Thus, there is a need for more epidemiological studies and education related to coeliac disease.     

Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis

BACKGROUND: Infection of pancreatic necrosis by gut bacteria is a major cause of morbidity and mortality in patients with severe acute pancreatitis. Use of prophylactic antibiotics remains controversial. The aim of this experiment was assess if modification of intestinal flora with specifically designed multispecies probiotics reduces bacterial translocation or improves outcome in a rat model of acute pancreatitis. METHODS: Male Sprague-Dawley rats were allocated into 3 groups: (1) controls (sham-operated, no treatment), (2) pancreatitis and placebo, and (3) pancreatitis and probiotics. Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Daily probiotics or placebo was administered intragastrically from 5 days prior until 7 days after induction of pancreatitis. Tissue and fluid samples were collected for microbiologic and quantitative real-time PCR analysis of bacterial translocation. RESULTS: Probiotics reduced duodenal bacterial overgrowth of potential pathogens (Log(10) colony-forming units [CFU]/g 5.0 +/- 0.7 [placebo] vs 3.5 +/- 0.3 CFU/g [probiotics], P < .05), resulting in reduced bacterial translocation to extraintestinal sites, including the pancreas (5.38 +/- 1.0 CFU/g [placebo] vs 3.1 +/- 0.5 CFU/g [probiotics], P < .05). Accordingly, health scores were better and late phase mortality was reduced: 27% (4/15, placebo) versus 0% (0/13, probiotics), respectively, P < .05. CONCLUSIONS: This experiment supports the hypothesis that modification of intestinal flora with multispecies probiotics results in reduced bacterial translocation, morbidity, and mortality in the course of experimental acute pancreatitis.     

The effect of 5-HTT gene promoter polymorphism on impulsivity depends on family relations in girls

The short (S) allele of the 5-HTT gene promoter region polymorphism (5-HTTLPR), in combination with adverse environmental influence, leads to higher likelihood of depression. Impulsivity has been related to low serotonin turnover, poor regulation of affect, and problems in the family, including child maltreatment. The current study explored the effect of the 5-HTTLPR polymorphism in the serotonin transporter gene and adverse family environment on impulsivity in adolescents. Healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study (n=483) filled the Adaptive and Maladaptive Impulsivity Scale (AMIS), Barratt Impulsiveness Scale (BIS-11), a scale measuring family relations, and were genotyped. While genotype alone was not associated with thoughtlessness, BIS-11 impulsiveness, fast decision-making or excitement seeking, 5-HTTLPR S allele carriers, however, had higher scores of disinhibition. In girls carrying the S allele, scores of thoughtlessness and disinhibition depended on family relations, being higher with less warmth in the family. Adverse family relations had no effect on impulsivity in girls with LL genotype. In boys, the effects of family relations on maladaptive impulsivity did not depend on genotype. However, the S allele and high maltreatment in the family both independently increased disinhibition and the BIS-11 score in boys. Family environment and the 5-HTTLPR genotype had no interactive effect on excitement seeking or fast decision-making. In summary, carrying the S allele may lead to high maladaptive impulsivity due to higher sensitivity to environmental adversity, which is more significantly expressed in girls.