PINK1 mutations in sporadic early-onset Parkinson's disease.

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.     

Relationship of AIDS-related attitudes to sexual behavior changes in adolescents.

The impact of the acquired immunodeficiency syndrome (AIDS) epidemic on a group of adolescents was investigated by surveying 197 sexually active, predominantly African-American, urban high school students. Reported sexual behavior changes were evaluated in relation to AIDS-related knowledge and attitudes. Over 50% of the students decreased their frequency of sexual activity, increased their condom use, and/or decreased their number of partners. These students had significantly higher scores on a measure of worry about vulnerability to human immunodeficiency virus (HIV) infection than those whose behavior had not changed. AIDS knowledge, AIDS beliefs, and AIDS-related anxiety interacted with gender to affect sexual behavior change. Male students reporting decreased frequency of sexual activity, for example, had more accurate beliefs about AIDS than males reporting no decrease. Among female students, however, those reporting decreased frequency had less accurate beliefs than those reporting no decrease. These results highlight the importance of considering gender and specific sexual behaviors when designing AIDS education interventions.     

Physical and Sexual Abuse and their Relation to Psychiatric Disorder and Suicidal Behavior among Adolescents who are Psychiatrically Hospitalized

Adolescents who were psychiatrically hospitalized ( N = 105) were classified as sexually abused, physically abused, both sexually and physically abused, or not abused, and studied to determine the prevalence of suicidal behavior and psychiatric disorders. Self-reports of hopelessness, depression, coping, and self-concept were also examined. No difference in suicidal behavior or psychiatric disorder, based on abuse history, was found, with one exception. Adolescents who were sexually abused, particularly those who experienced the most severe sexual abuse, used negative coping strategies more often than those not sexually abused. Findings suggest that symptomatology of adolescents who are psychiatrically hospitalized does not differ markedly based on history of abuse.     

3(S)-hydroxy-leukotriene B4 is a potent granulocyte chemotaxin in the guinea pig dermis

Inflammation Research -     

Antiinflammatory effects of second-generation leukotriene B4 receptor antagonist,SC-53228: Impact upon Leukotriene B4- and 12(R)-HETE- mediated events

Leukotriene B₄ (LTB₄) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] are proinflammatory products of arachidonic acid metabolism that have been implicated as mediators in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB₄ and 12(R)-HETE elicit a dose-dependent migration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 {7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxyl]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid}, a first-generation LTB₄ receptor antagonist, inhibited the chemotactic actions of LTB₄ when given orally with an ED₅₀ value of 1.7 mg/kg. The second-generation LTB₄ receptor antagonist, SC-53228 [(+)-(S)-7-(3-{2-(cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl]phenoxy} propoxy)-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propanoic acid], inhibited LTB₄-induced chemotaxis when given intragastrically with an ED₅₀ value of 0.07 mg/kg. Furthermore, SC-53228 inhibited 12(R)-HETE-induced granulocyte chemotaxis with an oral ED₅₀ value of 5.8 mg/kg. When dosed orally over a range of 0.03–100 mg/kg, SC-53228 gaveC _max plasma concentrations of 0.015–41.1g/ml. SC-53228 inhibited LTB₄-primed membrane depolarization of human neutrophils with an IC₅₀ value of 34 nM. As a potent LTB₄ receptor antagonist, SC-53228 may well have application in the medical management of disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease, contact dermatitis, and psoriasis, in which LTB₄ and/or 12(R)-HETE are implicated as inflammatory mediators.     

Temporal relationships of cytokine production in mouse non-lethal sepsis: Effect of nitric oxide synthase inhibitors

Inflammation Research -     

Modulation of the chemotactic properties of complement fragments C5a and C3 by the anti-inflammatory agent,SC-41930

Cleavage of the fifth component of complement yields C5a, a potent neutrophil (PMN) and eosinophil chemoattractant, and modulator of microvascular permeability. Similarly, but to a lesser degree, C3 increases vascular permeability and histamine release. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid), an orally-active antiinflammatory agent was tested in anin vivo model of dermal PMN chemotaxis induced by r-hu-C5a and hu-C3. Intradermal injection of C5a in the guinea pig resulted in a significant dose-dependent influx of PMNs at 4 hours as assessed by the dermal levels of myeloperoxidase (MPO). SC-41930 (20 mg/kg) given orally to guinea pigs with intradermal injections of 1 μg C5a significantly (p<0.001) reduced dermal MPO content. SC-41930 was less potent against C3, requiring 40 mg/kg to significantly reduce dermal MPO levels. Agents such as SC-41930, which nullify complement's proinflammatory properties, may well have therapeutic potential.     

Evaluation of a Standard Protocol for Retentive Encopresis: A Replication

Replicated the efficacy of a short-term, combined medical andbehavioral intervention protocol for retentive encopresis. Fifty-ninechildren who had failed standard medical management for retentiveencopresis and their parents participated in six 1-hour grouptreatment sessions. Treatment protocol combined the medicalmanagement strategies of enema clean out, increasing dietaryfiber, and daily toilet sitting with the child behavior managementstrategies of differential attention, contingency management,and contracting. For the overall sample, the number of soilingincidents decreased 85%, the weekly frequency of independentbowel movements increased 15%, the weekly frequency of parent-promptedbowel movements increased 9%, and daily dietary fiber intakeincreased 121% pre-to posttreatment. The majority of the sample(86%) stopped soiling by the end of treatment and did not requirefurther treatment. Results are discussed in terms of the comparabilitywith previous findings and the utility of combined medical andpsychological treatments for children with encopresis who havefailed standard medical approaches