ROLE OF ACULASER THERAPY IN CEREBRAL PALSY CHILDERN （INITIAL DATA ＆ RESULTS）

1　BACKGROUNDTheincidenceofCPis 0 .7per 1 0 0 0livebirths[1 ] .Becausecerebralpalsyinfluencesthewaychildrendevelop,itoftenresultsindevelop mentaldisability .Today ,more peoplehavecerebralpalsythananyotherdevelopmentaldis ability ,includingDownsyndrome,epilepsy ,andautism .Accordingtoasurveyconductedin1 986,2 .6%ofthepopulationofPakistaniaredisabled (includingbothphysicalandmentaldis abilities) .Childrenbetween 0～1 4 yearsinageconstitute 40 %ofthedisabled populationinPakistan .Routineme…     

Effect of a cognitive behavioral intervention on reducing symptom severity during chemotherapy.

PURPOSE: To describe a randomized trial of a cognitive behavioral intervention on reducing symptom severity among patients diagnosed with solid tumors and undergoing a first course of chemotherapy and to determine whether the intervention had an additive or interactive effect on symptom severity in the presence of supportive care medications. PATIENTS AND METHODS: Patients (N = 237) were accrued from comprehensive and community cancer centers, interviewed, and randomly assigned to either the experimental intervention (n = 118) or conventional care (n = 119). A symptom severity index, based on summed severity scores across 15 symptoms, was the primary outcome. Each patient's site of cancer, stage at diagnosis, chemotherapy protocols, and use of supportive medications were learned from medical records. RESULTS: Groups were equivalent at baseline, and attrition by characteristics by group was not different. The proportion of patients not receiving chemotherapy at 10 and 20 weeks did not differ by group. At the 10- and 20-week observations, there was a significant interaction between the experimental group and baseline symptom severity. Patients in the experimental group who entered the trial with higher symptom severity reported significantly lower severity at 10 and 20 weeks. Controlling for chemotherapy treatment status at follow-up and supportive care medications did not alter the effect of the experimental intervention. CONCLUSION: Compared with conventional care alone, the experimental intervention was effective among patients who entered the trial with higher levels of symptom severity. Age, sex, site or stage of cancer, and supportive medications did not modify the effect of this cognitive behavioral intervention on symptom severity.     

Preclinical evaluation of 2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]-propionic acid as a modulator of etoposide in human Waldenstrom's macroglobulinemia xenograft model.

We have previously reported that XK469 (2-[4-(7-chloro-2-quinoxalinyloxyphenoxy]-propionic acid) enhances topo IIalpha expression in WSU-WM cells in vitro [E. Mensah-Osman et al., Mol. Cancer Ther., 1: 1321-1326, 2002]. To test the hypothesis that XK469-induced expression of topo IIalpha sensitizes WSU-WM cells to the topo IIalpha inhibitor etoposide (VP-16), we investigated the antitumor effects of XK469 and VP-16 in vivo, using the WSU-WM SCID xenograft model. Individual dosages of XK469 at 20-60 mg/kg/injection i.v. for a maximum-tolerated dose of 240 mg/kg were achievable in SCID mice. Simultaneous administration of a subtherapeutic dose of XK469 (20 mg/kg) and VP-16 at its maximum-tolerated dose of 15 mg/kg proved to be highly toxic and lethal. However, daily sequential treatment of XK469 given i.v. via tail vein at 20 mg/kg for a total of 120 mg/kg, followed 7 h later by VP-16 i.p. at 15 mg/kg for a total of 90 mg/kg, had no significant toxicity in SCID mice. The sequential treatment was associated with enhanced antitumor activity. Tumor growth inhibition T/C, tumor growth delay T-C, and log(10) kill for XK469 alone were 61%, 3 days and 0.46; VP-16 alone 6%, 12 days and 1.83, respectively; whereas the sequential administration of both agents gave a T/C value of 0%, T-C value of 23 days and a log(10) kill of 3.5. On the basis of these animal results, we conclude that the sequential treatment of WSU-WM tumors with XK469 and VP-16 was highly active. The study supports our in vitro observation that XK469 potentiates VP-16 activity. The sequential use of both agents resulted in clinically significant antitumor activity in the WM model.     

Household and environmental factors influencing anthropometric outcomes in preschool children in a rural Ethiopian community

This article tests the hypothesis that anthropometrical outcomes in preschool children are a function of complex interaction between food, nutrition, health, and other physical environmental conditions within which children live and grow. A system of simultaneous equations is used to test the above hypothesis using data from an Ethiopian highland community. The results show that a child's nutritional and health status are jointly determined by dietary intake, well-being of the mother as the primary caregiver, and the state of the physical environment for agricultural production and healthy living. Among other factors, children were found to be in better health with an increase in the number of cows in their households' livestock herds. The revealed interrelatedness and complexities of cause and effect clearly dictate the need for a multi- or transdisciplinary approach to research and development addressing health, nutrition, sanitation, agricultural production practices, among other factors for alleviating the nutritional and health problems of children and rural households.     

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.     

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.     

Brief Report: Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration–approved A_2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.