Potential of ezetimibe in memory deficits associated with dementia of Alzheimer's type in mice

Background:

High cholesterol levels have been positively correlated with a higher incidence of memory impairment and dementia.

Aim:

The study was undertaken to investigate the potential of the lipid-lowering drug, ezetimibe, in memory deficits associated with dementia of Alzheimer''s (AD) type in mice.

Methods:

Dementia was induced with chronic administration of a high-fat diet (HFD) or intracebroventricular streptozotocin (ICV STZ, two doses of 3 mg/kg) in separate groups of animals. The memory of the animals was assessed by employing a Morris water maze. Brain thio barbituric acid-reactive species and reduced glutathione levels were measured to assess the total oxidative stress. Brain acetyl cholinesterase (AChE) activity and total serum cholesterol levels were also measured.

Results:

STZ/HFD produced a significant impairment of memory along with an increase in brain AChE activity and oxidative stress. HFD mice also showed an increase in cholesterol levels. Ezetimibe (10 mg/kg, orally for 15 days) significantly attenuated STZ/HFD-induced memory deficits and biochemical changes. It also prevented HFD-induced rise in the cholesterol level.

Conclusions:

The memory-restorative effect of ezetimibe can be attributed to its cholesterol-dependent as well as cholesterol-independent effects. The study highlights the potential of ezetimibe in memory dysfunctions associated with dementia of AD.     

Mechanical reperfusion is associated with post-ischemic hemorrhage in rat brain

A major complication of recanalization therapy after an acute arterial occlusion in brain is hemorrhagic transformation (HT). Although it is known that prolonged ischemia is important in the development of HT, the role of reperfusion in ischemia–reperfusion induced HT is less well studied. To address the effect of reperfusion on HT, we assessed the incidence and severity of hemorrhage in rats after 5 h of middle cerebral artery occlusion (MCAO) followed by 19-hour reperfusion compared to rats with permanent occlusion (PMCAO) at the same 24-hour time point. The incidence and amount of hemorrhage, neurological function, and mortality rates were measured. MCAO (5 h) with 19-hour reperfusion was associated with a significantly higher incidence of cortical hemorrhage compared to PMCAO (81.8% vs 18.2%, p < 0.05). Hemorrhage scores were higher in the 5-hour MCAO/reperfusion group compared to PMCAO rats (17.6 ± 11.5 vs 2.4 ± 5.3 in cortex, 20.4 ± 4.6 vs 9.7 ± 4.5 in striatum, p < 0.01). Neurological function was worse in the ischemia–reperfusion group compared to PMCAO (p < 0.05) and mortality rates were insignificantly higher in the 5-hour MCAO/reperfusion group vs PMCAO group (54.5% vs18.1%; p < 0.08). The results suggest that reperfusion after prolonged ischemia is associated with increased hemorrhagic transformation and neurological deterioration as compared to permanent ischemia. Whether pharmacological treatments prior to reperfusion attenuate post-ischemic HT requires further study.     

Maternal substance use and HIV status: adolescent risk and resilience

We examined the risk and protective factors and mental health problems of 105 low SES, urban adolescents whose mothers were coping with alcohol abuse and other drug problems. Approximately half of the mothers were also HIV-infected. As hypothesized, there were few differences between adolescents of HIV-infected and HIV-uninfected mothers in background characteristics, mental health issues and current substance use risk behaviors. In addition to maternal substance abuse, youth in both groups experienced similar risk factors including early foster care placement and high levels of maltreatment. Current patterns of emerging risk behaviors were evident among youth in both groups as well as signs of resiliency including high levels of school attendance. These results underscore the importance of interventions for youth of substance abusing mothers, particularly those living in urban poverty.     

Recent Update on Bacteria as a Delivery Carrier in Cancer Therapy: From Evil to Allies

Pharmaceutical Research - Cancer is associated with a comprehensive burden that significantly affects patient’s quality of life. Even though patients’ disease condition is improving...     

'Dhat' syndrome--a useful clinical entity

48 consecutive male patients of potency disorders were examined and classified as 'Dhat' syndrome, impotence or premature ejaculation. The age range of these cases was found as 20-38 years (mean 23.5 +/- 3.3 years) while age of onset was 16-24 years (mean 20.6 +/- 4.5 years). Majority of cases were unmarried (54.2%) and educated 5th class or above (79.1%). 31 cases (64.6%) had Dhat syndrome with or without impotency and/or premature ejaculation while 7 cases (14.6%) had only premature ejaculation and 10 cases (20.8%) only impotence. The cases with 'Dhat' syndrome or with impotence scored maximally on neuroticism and depression scales. Neurotic depression was the commonest associated psychiatric illness (39.5%) followed by anxiety neurosis (20.8%) while 31.3% did not have any possible diagnosis. The common presenting symptoms of 'Dhat' syndrome include weakness (70.8%), fatigue (68.7%), palpitations (68.7%), sleeplessness (62.4%) etc. Among the four groups on the basis of type of treatment (antianxiety drug, antidepressant, placebo, psychotherapy), the best response was seen in those receiving antianxiety or antidepressant drugs while those receiving psychotherapy showed minimal response. 7 cases (14.6%) dropped out of treatment and the maximum dropout (40.6%) was seen in psychotherapy group.     

Clinical stage after preoperative chemoradiation is a better predictor of patient outcome than the baseline stage for localized gastric cancer

BACKGROUND: For patients with localized gastric cancer (LGC) who are receiving preoperative chemoradiation (CTRT), the postsurgical pathologic stage predicts overall survival (OS) better than the baseline stage. The authors hypothesized that presurgical (postCTRT) stage would also correlate better with patient outcome than the baseline stage. METHODS: The authors analyzed 74 LGC patients treated with preoperative CTRT receiving similar treatment. Patients were staged with baseline endoscopic ultrasonography (EUS) and laparoscopy. Patients received induction chemotherapy, then CTRT (45 Gy), and had an attempted surgery. After CTRT, patients had complete preoperative staging including EUS in 35 patients. RESULTS: Thirty-five had all 3 sets of staging, baseline, presurgical, and postsurgical. Baseline stage did not associate with OS (P = .16) nor disease-free survival (DFS; P = .13). However, presurgical stage was associated with OS (P = .01), and DFS (P = .05). OS was also associated with postsurgical stage and was longer for stages 0 and I than for stages III and IV (P = .01 and .04, respectively). Similarly, DFS was longer in postsurgical pathologic stages 0, I, and II than in stage III or IV (P < .001, <.001, and <.01, respectively). Baseline staging did not correlate with the proportion of patients alive at 4 years; however, presurgical staging did. Patients with stage I or II survived longer than those with stage III or IV (81% vs 25%; P < .01). CONCLUSIONS: Heterogeneity in clinical biology of LGC is best reflected after CTRT in presurgical and postsurgical pathologic stages rather than by the baseline stage. Correlation of outcome with presurgical staging may facilitate strategies to individualize therapy for LGC.     

Effect of timing of metastasis/disease recurrence and histologic differentiation on survival of patients with advanced gastric cancer

BACKGROUND: Patients with advanced gastric cancer have a median survival (MS) of <9 months. It is unclear whether the MS of patients who have advanced cancer at the time of diagnosis (synchronous, Group A) is different from that for patients who develop advanced cancer after curative surgery (metachronous, Group B). It was hypothesized that survival would be similar. METHODS: The medical records of all patients treated at the University of Texas M. D. Anderson Cancer Center who were in either Group A or Group B were reviewed. Survival of patients was assessed by the Kaplan-Meier method. A Cox proportional hazards model was used for multivariate hazards ratios that were adjusted for the effects of location of recurrence, histologic differentiation, patient sex and age, the location of the primary tumor, and timing of disease recurrence (Group A or Group B) on survival. RESULTS: In all, 773 consecutive patients qualified for the analysis. The distribution of age, race, histologic differentiation, and primary tumor location was similar in both groups. The MS of Group A (n = 603 patients) and Group B (n = 170 patients) was the same (7.6 months). Similarly, the location of the primary tumor and patient sex were found to have no impact on survival. Patients with poorly differentiated tumors (World Health Organization grade 3 or 4) were found to have a shorter survival compared with those with well-differentiated or moderately differentiated tumors (grade 1 or 2; P = .004). Patients with distant metastases had a shorter survival (P = .01) than those with locoregional disease recurrence. CONCLUSIONS: The data show that MS is similarly poor in patients with advanced gastric cancer with synchronous metastasis (Group A) or those with metachronous metastasis/disease recurrence (Group B). Poor differentiation and anatomically distant site of metastasis were found to impact MS adversely.