Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol.

There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D(2)/D(3) receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors. We performed [(18)F] fallypride PET studies in six schizophrenic subjects treated with olanzapine and six schizophrenic subjects treated with haloperidol to examine the occupancy of striatal and extrastriatal dopamine receptors by these antipsychotic drugs. [(18)F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT(2A) receptor occupancy. Occupancy of dopamine D(2)/D(3) receptors by olanzapine was not significantly different from that seen with haloperidol in the putamen, ventral striatum, medial thalamus, amygdala, or temporal cortex, that is, 67.5-78.2% occupancy; olanzapine produced no preferential occupancy of dopamine D(2)/D(3) receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D(2)/D(3) receptors in olanzapine-treated compared to haloperidol-treated subjects, that is, 40.2 vs 59.3% (p=0.0014, corrected for multiple comparisons); in olanzapine-treated subjects, the substantia nigra/VTA was the only region with significantly lower dopamine D(2)/D(3) receptor occupancy than the putamen, that is, 40.2 vs 69.2% (p<0.001, corrected for multiple comparison). Occupancy of 5-HT(2A) receptors was 85-93% in the olanzapine- treated subjects. The results of this study demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D(2)/D(3) receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.     

Neurodegenerative disorder and diffuse brain calcifications due to FARSB mutation in two siblings

Pathogenic mutations in the FARSB gene are associated with neurodevelopmental disorder involving the brain, liver, and lungs. We report genetic analysis of a family including two affected members with this disorder, which revealed a homozygous pathogenic missense variant, FARSB: {"type":"entrez-nucleotide","attrs":{"text":"NM_005687.4","term_id":"743405629","term_text":"NM_005687.4"}}NM_005687.4:c.853G > A:p.E285K in both affected patients. The parents were heterozygous for this variant.     

Correlation of vitreous chamber depth with ocular biometry in high axial myopia

Purpose:The proportion of axial length (AL) occupied by vitreous chamber depth (VCD), or VCD:AL, consistently correlates to ocular biometry in the general population. Relation of VCD:AL to ocular biometry in high myopia is not known. The purpose of this study is to evaluate the relation of VCD and VCD:AL to ocular biometry of highly myopic eyes.Methods:This was a cross-sectional retrospective study of records of 214 myopic eyes (<−1 D SE, aged 20–40 years) attending the refractive surgery services. High axial myopia was defined as AL >26.5 mm. Eyes with posterior staphyloma and myopic maculopathy were excluded. Records were assessed for measurements of AL, central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white to white diameter (WTW), and vitreous chamber depth (VCD). Groups were formed based on increasing AL, while the sum of CCT, ACD, and LT was recorded as anterior segment depth (AS). The main outcome measure was the correlation of VCD and VCD:AL to ocular biometry. A comparison was also performed based on of degree of axial myopia.Results:Mean age of the patients was 27.0 ± 5.2 years. VCD showed a very strong correlation with AL (R = 0.98, P < 0.001) but did not correlate to any anterior parameter. VCD:AL showed moderate negative relation with AS (R = −0.43, P < 0.001) and ACD (R = −0.3, P < 0.001), while it had a weakly negative relation with LT (R = −0.18, P = 0.006). VCD:AL showed strong negative relation (R > ~0.7) with AS in all individual groups of AL. Among anterior parameters, WTW showed the most consistent relation with ocular biometry.Conclusion:VCD:AL is a better correlate of ocular biometry in high myopia as compared to VCD. However, the correlation is weaker than that noted by previous studies done on the general population. Longitudinal studies of VCD:AL in the younger age group is recommended.     

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC₅₀ of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC₅₀ 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.     

Periorbital ecchymosis as a sign of perforating injury of the globe

The distinction between penetrating eye injury with retained intraocular foreign body and perforating globe injuries is not always easy clinically. The case is presented of a 25-year-old man who sustained a perforating eye injury that was through a clear self-sealing corneal entry site and had no conjunctival or periorbital injury. He had periorbital ecchymosis on presentation suggesting that the globe had been perforated with resulting retro-orbital blood tracking to the periorbital region. This sign would not be expected had the foreign body remained intraocular. The management options of these cases are discussed.     

Superior quality chemically reduced graphene oxide for high performance EMI shielding materials

The chemical reduction process of graphene oxide combined with a mild and controllable thermal treatment under vacuum at 200 °C for 4 hours provided a cost-effective, scalable, and high-yield route for Reduced Graphene Oxide (RGO) industrial production and became a potential candidate for producing electromagnetic interference (EMI) shielding. We investigated graphite, and RGO using l-ascorbic acid and Sodium borohydride before and after thermal treatment by carefully evaluating the chemical and morphological structures. The thermally treated l-ascorbic Acid reduction route (TCRGOL) conductivity was 2.14 × 10³ S m⁻¹ and total shielding efficiency (SET) based on mass loadings per area of shielding was 94 dB with about one-tenth less graphite weight and surpassing other graphene reduction mechanisms in the frequency range of 8.2–12.4 GHz, i.e., X-band, at room temperature while being tested using the waveguide line technique. The developed treatment represents valuable progress in the path to chemical reduction using a safe reducing agent and offering superior quality RGO rarely achieved with the top-down technique, providing a high EMI shielding performance.

The developed two-step protocol offers a superior reduced graphene oxide TCRGOL quality (7 layers), and its SET was 94 dB over the X-band.