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A series of genipin derivatives included tricyclic cyclopentaimidazopyridine, cyclopentapyridopyrimidine, octahydrocyclopentapyridodiazepine, and tetracyclic decahydrobenzoimidazocyclopentapyridine were synthesized and developed as anti-inflammatory agents. All of them were tested against NO production in LPS-induced RAW264.7 cells. Based on IC

Background: Type-2 diabetes is a chronic progressive metabolic disease resulting in severe vascular complications and mortality risk. Recently, DPP-4 inhibitors are conceived as a favorable class of agents for the treatment of type 2 diabetes due to the minimal side effects. Methods: Sitagliptin is the first medicine approved for DPP-4 inhibitor. Its structure involved three fragments: 2,4,5-triflorophenyl fragment pharmacophore, enantiomerically β-amino carbonyl linker, and tetrahydrotriazolopyridine. Herein, we are drawn to the possibility of substituting tetrahydrotriazolopyridine motif present in Sitagliptin with a series of new fused pyrazolopyrimidine bicyclic fragment to investigate potency and safety. Results: Two series of fused 6-(aminomethyl)pyrazolopyrimidine and 6-(hydroxymethyl)pyrazolopyrimidine derivatives containing β-amino ester or amide as linkers were successfully designed for the new DPP-4 inhibitors. Most fused 6-methylpyrazolopyrimidines were evaluated against DPP-4 inhibition and selectivity capacity. Based on research study, β-amino carbonyl fused 6-(hydroxymethyl)pyrazolopyrimidine possesses the significant DPP-4 inhibition (IC50 ≤ 59.8 nM) and presents similar with Sitagliptin (IC50 = 28 nM). Particularly, they had satisfactory selectivity over DPP-8 and DPP-9, except for QPP. Conclusion: β-Amino esters and amides fused 6-(hydroxymethyl)pyrazolopyrimidine were developed as the new DPP-4 inhibitors. Those compounds with a methyl group or hydrogen in N-1 position and methyl substituted group in C-3 of pyrazolopyrimidine moiety showed better potent DPP-4 inhibition (IC50 = 21.4–59.8 nM). Furthermore, they had satisfactory selectivity over DPP-8 and DPP-9 Finally, the docking results revealed that compound 9n was stabilized at DPP-4 active site and would be a potential lead drug.

Background Obsessive-compulsive disorder (OCD) is a neuropsychiatric illness with frequent childhood onset and notable gender differences. Anecdotally, male OCD-affected youth frequently report concerns about short stature, resulting in endocrinology consultation. Initial reports have described this phenomenon, yet none have systematically analyzed potential confounders for this observation or examined for this in adults. Determining whether short stature is truly associated with OCD among adolescent males is important given its emotional impacts and costs of potentially unnecessary medical evaluations. This may also inform future studies of the potential complex etiologic overlaps between OCD, neuroendocrine pathophysiology and genetic risk variants. Methods A total of 42 adolescents (9–20 years old) were recruited from a tertiary Pediatric OCD clinic between 2008 and 2010. Subjects with a DSM-IV OCD diagnosis who provided voluntary informed consent/assent were included; those with comorbid eating disorders were excluded. Height and weight were measured and transformed into percentiles using the US CDC growth census database (NHANES 2000). Clinical variables were compared by gender via the Fisher's exact test using a significance threshold of p Results The mean height percentile was 33.9% (SD 29.6) for male and 51.5% (SD 31.1) for female adolescents, with significantly more cases of short stature ( p =0.004). Comparative analyses demonstrated no significant confounding gender differences accounting for observed height differences ( p >0.05). After adjusting for important clinical covariates, including serotonin reuptake inhibitor (SRI) use, psychostimulant use, and Tourette history, short stature remained strongly associated with male gender (OR=7.4; 95% CI: 1.5–36.6; p =0.01). This gender difference was not found in a comparable adult sample ( p =0.45), which had no elevated incidence of short stature. Conclusions Short stature is common among adolescent OCD-affected males but not females, and appears to normalize by adulthood. This feature does not appear to be attributable to confounding clinical factors such as medication use.

Objective Familial aspects of pediatric obsessive-compulsive disorder (OCD), including accommodation and treatment, have received notable and warranted attention. However, individual perspectives of its repercussions on family functioning, including emotional and occupational parental burden, have not been closely examined. The present study details this topic using a large multicenter sample. Method Participants included 354 youth affected with OCD and their mothers and fathers ascertained through OCD programs in Boston, Massachusetts (n = 180) and Vancouver, British Columbia (n = 174). The validated OCD Family Functioning Scale and standard OCD measurements were completed. Descriptive, between-site, and cross-perspective comparative analyses were followed by regression model testing to predict family impairment. Results Family functioning was negatively affected from youth, mother, and father perspectives. Impairment was reportedly more extensive at the time of worst OCD severity and was greater from maternal versus paternal viewpoints. Most frequently affected family tasks and implicated OCD symptoms included morning and bedtime routines and intrusive thoughts. Emotional repercussions in all members included stress and anxiety, followed by frustration or anger in youth and sadness in parents. Nearly half of mothers and one third of fathers reported daily occupational impairment. Compared with youth self-report, parents perceived fewer social and academic effects on their child. Family accommodation most consistently predicted family impairment, especially from parent perspectives. OCD and compulsion severity, contamination and religious obsessions, and comorbidities also predicted various perspectives of family subdomain impairment. Conclusion This study quantitatively details the pervasive burden that pediatric OCD places on families, as reported from complementary relative perspectives. Further attention to this topic is warranted in clinical and research realms.

Obsessive–compulsive disorder (OCD) influences not only patients but also family members. Although the construct of family accommodation has received attention in OCD literature, no measures of overall family functioning are currently available. The OCD Family Functioning (OFF) Scale was developed to explore the context, extent, and perspectives of functional impairment in families affected by OCD. It is a three-part, self-report measure capturing independent perspectives of patients and relatives. A total of 400 subjects were enrolled between 2008 and 2010 from specialized OCD clinics and OCD research studies. Psychometric properties of this scale were examined including internal consistency, test–retest reliability, convergent and divergent validity, and exploratory factor analyses. Both patient and relative versions of the OFF Scale demonstrated excellent internal consistency (Cronbach’s alpha coefficient = 0.96). The test–retest reliability was also adequate (ICC = 0.80). Factor analyses determined that the OFF Scale comprises a family functioning impairment factor and four OCD symptom factors that were consistent with previously reported OCD symptom dimension studies. The OFF Scale demonstrated excellent convergent validity with the Family Accommodation Scale and the Work and Social Adjustment Scale. Information gathered regarding emotional impact and family role-specific impairment was novel and not captured by other examined scales. The OFF Scale is a reliable and valid instrument for the clinical and research assessment of family functioning in pediatric and adult OCD. This will facilitate the exploration of family functioning impairment as a potential risk factor, as a moderator and as a treatment outcome measure in OCD.