3-MHPG as a non-predictor of antidepressant response to imipramine and electroconvulsive therapy

The urinary excretion of 3-methoxy, 4-hydroxyphenyl-glycol, (3-MHPG) was measured in 20 unipolar depressed patients before treatment with imipramine and electroconvulsive therapy (ECT) to investigate the relationship between pretreatment urinary excretion of 3-MHPG and clinical response. There was no difference in 3-MHPG excretion for depressed patients and controls. There was no significant difference between the mean percentage reduction of Hamilton Depression Rating Scale Scores in "low" and "high" excretors of 3-MHPG in the imipramine and ECT group of patients after four weeks of treatment.     

Formulation and evaluation of novel tableted chitosan microparticles for the controlled release of clozapine

Controlled release formulations of clozapine microparticulated tablets were prepared by using chitosan. Microparticles were characterized for particle size and size distribution. Microparticles were compressed into tablets using the directly compressible excipients. SEM photographs of the fractured part of the tablet revealed the presence of discrete particles in the tablets, suggesting that the system chosen is ideal for tableting. Drug release from the tableted microparticles exhibited an initial burst effect, but the release decreased with increasing extent of cross-linking. Tablets were coated with chitosan or cellulose acetate, which significantly lowered the initial burst effect when compared to uncoated tablets. Drug release from chitosan-coated tablets was slightly higher than the tablets coated with cellulose acetate. Tablets prepared were effective in delivering clozapine over a period of 12?h.     

Recurrence of progressive multifocal leukoencephalopathy despite immune recovery in two HIV seropositive individuals

We present two cases of recurrent progressive multifocal leukoencephalopathy (PML) in patients with long standing virally suppressed human immunodeficiency virus (HIV) and normal CD4+ T cell count who were taking stable regimens of highly active antiretroviral therapy (HAART). This has significant implications for other patients with a past history of PML, not just those with HIV but also those on medications such as natalizumab or fumarates.     

Loss of p53 cooperates with K‐ras activation to induce glioma formation in a region‐independent manner

Gliomas are recognized as a heterogeneous group of neoplasms differing in their location and morphological features. These differences, between and within varying grades of gliomas, have not been explained solely on the grounds of an oncogenic stimulus. Interactions with the tumor microenvironment as well as inherent characteristics of the cell of origin are likely a source of this heterogeneity. There is an ongoing debate over the cell of origin of gliomas, where some suggest a progenitor, while others argue for a stem cell origin. Thus, it is presumed that neurogenic regions of the brain such as the subventricular zone (SVZ) containing large numbers of neural stem and progenitor populations are more susceptible to transformation. Our studies demonstrate that K‐ras^G12D cooperates with the loss of p53 to induce gliomas from both the SVZ and cortical region, suggesting that cells in the SVZ are not uniquely gliomagenic. Using combinations of doxycycline‐inducible K‐ras^G12D and p53 loss, we show that tumors induced by the cooperative actions of these genes remain dependent on active K‐ras expression, as deinduction of K‐ras^G12D leads to complete tumor regression despite absence of p53. These results suggest that the interplay between specific combinations of genetic alterations and susceptible cell types, rather than the site of origin, are important determinates of gliomagenesis. Additionally, this model supports the view that, although several genetic events may be necessary to confer traits associated with oncogenic transformation, inactivation of a single oncogenic partner can undermine tumor maintenance, leading to regression and disease remission. GLIA 2013;61:1862–1872     

Acute and subchronic dermal toxicity of Vitex negundo essential oil

Vitex negundo is a common herb in different herbal formulation. The potential acute and sub-chronic dermal toxicities were evaluated as per OECD (Organization for Economic Cooperation and Development) guidelines 402 and 411, respectively. Both sexes of Wistar rats were exposed to Vitex negundo oil of 2000?mg/kg body weight for acute dermal toxicity, whereas in the dermal sub-chronic toxicity study, rats were exposed to Vitex negundo oil 250, 500 and 1000?mg/kg body weight, respectively, for five times a week for 90?d. In acute and sub-chronic toxicity studies, all animals were normal without any behavioral, serum biochemistry, hematology, necroscopical and histopathological changes. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) of Vitex negundo oil were 250 and 1000?mg/kg/day, respectively. Vitex negundo oil is under the category 5 (Unclassified) according to the Globally Harmonized System, with an LD₅₀ value of over 2000?mg/kg.     

Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen

ObjectiveTo test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA).MethodsOverall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4 ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400 mg of ofloxacin and 20 mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography–guided biopsy was done only when PSA level did not decrease less than 4 ng/ml.ResultsMean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6678 pg/ml (SD±1985.7) than in control, i.e., 1543 pg/ml (SD±375.7) (P<0.001). Following anti-inflammatory treatment, there was a significant decrease in the mean level of IL-8 from baseline to 5622 pg/ml (SD±1870.66) (P<0.001). Corresponding to this, a significant decrease was noted in total PSA levels to less than 4 ng/ml in 105 (65.62%) patients. Men with the highest levels of IL-8 had a greater degree of erectile dysfunction.ConclusionMen with symptomatic benign prostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy.     

The long-term stability of new hippocampal place fields requires new protein synthesis

The hippocampus is critical for formation of spatial memories. Hippocampal pyramidal neurons in freely behaving animals exhibit spatially selective firing patterns, which taken together form an internal representation of the environment. This representation is thought to contribute to the hippocampal spatial memory system. Behavioral long-term memories differ from short-term memories in requiring the synthesis of new proteins. Does the development of the internal hippocampal representation also require the synthesis of new proteins? We found that blocking protein synthesis in the brain of mice by 95% does not affect short-term stability of newly formed hippocampal place fields but abolishes stability in the long term. By contrast, inhibiting protein synthesis does not affect the retention and recall of previously established fields in a familiar environment, indicating that protein synthesis-dependent reconsolidation is not required for recall. Our results indicate that place fields parallel both behavioral memories and the late phase of long-term potentiation in requiring the synthesis of new proteins for consolidation.     

Subtype B and subtype C HIV type 1 recombinants in the northeastern state of Manipur, India

The predominant HIV-1 strain circulating in India is subtype C. However, subtype A and B strains of HIV-1 have also been reported in India. In 1999, the first A/C recombinant strain was reported from Pune in India. Intravenous drug users (IVDUs) from the northeastern region of India have a high HIV-1 seroprevalence. Studies carried out in intravenous drug users in the northeastern region of India have shown that HIV-1 subtype C is the predominant strain infecting IVDUs. Fourteen blood samples were collected from HIV-1-infected individuals from the northeastern region of India and screened by env and gag heteroduplex mobility assays (HMA). Where the env and gag HMA results from a sample yielded different subtypes, sequencing of env and gag PCR products was carried out to confirm the presence of HIV-1 recombinants. Of the 14 samples subtyped, nine samples belonged HIV-1 subtype C (gag C/env C), one to HIV-1 subtype B (gag B/env B), and the remaining were B/C recombinants (gag C/env B). This is the first report of HIV-1 B/C recombinants from India.