Decreased dopamine activity predicts relapse in methamphetamine abusers.

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [(11)C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes

Management of Impotence After Treatment of Carcinoma of the Prostate

Impotence commonly occurs as a result of treatment of carcinoma of the prostate. We review the etiology, evaluation, and treatment options available for these patients as well as our experience with fifty prostate cancer patients who underwent placement of penile prostheses. Several excellent alternatives are available for patients with impotence resulting from treatment of carcinoma of the prostate

Brain monoamine oxidase A activity predicts trait aggression

The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the multidimensional personality questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than one-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression

Clinical Significance of Telomere Length and Associated Proteins in Oral Cancer

Purpose: Telomere shortening is an important event during carcinogenesis. Although studies suggest role of multiple proteins in telomere length regulation, there is dearth of reports in oral cancer which is a leading malignancy in Asian countries especially in India. Thus the present study was carried out to study these mechanisms and explore the pathways involved in telomere—telomerase regulation and identify possible prognostic markers to understand the biology of oral tumors for better treatment approaches. Methods: Telomere length was determined by Southern Hybridisation method, telomeric repeat binding factor (TRF) 1 and 2 expression was detected by Western blot method and telomerase activation by telomeric repeat amplifi cation protocol. Statistical analysis was done using SPSS (Version 10) software. Results: Significant shortening of telomeres was seen in the tumor tissues as compared to normal tissues. Poor prognosis was observed in the patients with higher telomere length in malignant tissue, higher tumor to normal telomere length ratio (T/N TRF LR). Expression of TRF-2 but not TRF-1 protein was signifi cantly higher in the malignant tissues. We also observed telomerase activation in 75 malignant tissues.Conclusions: Our results reveal signifi cant clinical usefulness of telomere length, T/N TRF LR and telomerase activation in the prognosis of oral cancer patients. TRF-2 overexpression in malignant tissues appears to play an important role in telomere length shortening in oral cancer. Abbreviations: TRF—Terminal restriction fragment; TRF-1—telomeric repeat binding factor-1; TRF-2—telomeric repeat binding factor-2; T/N TRF LR—Tumor/ Normal TRF length ratio

Optical conductivity of the metallic pyrochlore iridate Pr2Ir2O7: influence of spin-orbit coupling and electronic correlations on the electronic structure

The synergy of strong spin-orbit coupling and electron-electron interactions gives rise to unconventional topological states, such as topological Mott insulator, Weyl semimetal, and quantum spin liquid. In this study, we have grown single crystals of the pyrochlore iridate Pr$_2$Ir$_2$O$_7$ and explored its magnetic, lattice dynamical, and electronic properties. While Raman spectroscopy data reveal six phonon modes confirming the cubic \textit{Fd$\bar{3}$m} crystal symmetry, dc magnetic susceptibility data show no anomalies and hence indicate the absence of magnetic phase transitions down to 2~K. Both temperature-dependent electric transport and optical conductivity data reveal the metallic character of Pr$_2$Ir$_2$O$_7$. The optical conductivity spectrum contains a mid-infrared absorption band, which becomes more pronounced with decreasing temperature due to spectral weight transfer from high to low energies. The presence of the mid-infrared band hints at the importance of correlation physics. The optical response furthermore suggests that Pr$_2$Ir$_2$O$_7$ is close to the Weyl semimetal phase.11 pages, 8 figures, accepted for publication in Phys. Rev.

Fructose-2,6-Bisphosphate Synthesis by 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (PFKFB4) Is Required for the Glycolytic Response to Hypoxia and Tumor Growth

Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is over-expressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines. Although PFKFB4 appears to be a rational target for anti-neoplastic drug development, it is not clear whether its kinase or phosphatase activity is required for cancer cell survival. In this study, we demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater than its phosphatase activity, siRNA and genomic deletion of PFKFB4 decrease F2,6BP, PFKFB4 over-expression increases F2,6BP and selective PFKFB4 inhibition in vivo markedly reduces F2,6BP, glucose uptake and ATP. Last, we find that PFKFB4 is required for cancer cell survival during the metabolic response to hypoxia, presumably to enable glycolytic production of ATP when the electron transport chain is not fully operational. Taken together, our data indicate that the PFKFB4 expressed in multiple transformed cells and tumors functions to synthesize F2,6BP. We predict that pharmacological disruption of the PFKFB4 kinase domain may have clinical utility for the treatment of human cancers

Larval development of Metapenaeus moyebi (Kishinouye) reared in the laboratory

The complete larval development of Metapenaeus moyebi was studied by rearing them in the CMFRI laboratory at Karwar. The viable eggs take 8i to 10 hours to hatch out and the duration of nauplius stage ranges between 37 and 44 hours. The protozoea transforms into mysis after 5 to 5i days. The mysis stage lasts for 91/2 to lO1/2 days. Complete larval development from egg to postlarva I takes 16-181 days. There are 6 nauplius sub-stages, 3 protozoea substages, 3 mysis substages and 1 intermediate stage during the course of development. The detailed structure of the larval substages is described and illustrated in this paper

The oncoprotein H-RasV12 increases mitochondrial metabolism

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