Melatonin as a Neuroprotective Agent in the Rodent Models of Parkinson’s Disease: Is it All Set to Irrefutable Clinical Translation?

Parkinson’s disease (PD), a neurodegenerative disorder, is characterized by the selective degeneration of the nigrostriatal dopaminergic neurons, continuing or permanent deficiency of dopamine, accretion of an abnormal form of alpha synuclein in the adjacent neurons, and dysregulation of ubiquitin proteasomal system, mitochondrial metabolism, permeability and integrity, and cellular apoptosis resulting in rigidity, bradykinesia, resting tremor, and postural instability. Melatonin, an indoleamine produced almost in all the organisms, has anti-inflammatory, anti-apoptotic, and anti-oxidant nature. Experimental studies employing 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), methamphetamine, rotenone, and maneb and paraquat models have shown an enormous potential of melatonin in amelioration of the symptomatic features of PD. Although a few reviews published previously have described the multifaceted efficacy of melatonin against MPTP and 6-OHDA rodent models, due to development and validation of the newer models as well as the extensive studies on the usage of melatonin in entrenched PD models, it is worthwhile to bring up to date note on the usage of melatonin as a neuroprotective agent in PD. This article presents an update on the usage and applications of melatonin in PD models along with incongruous observations. The impending implications in the clinics, success, limitations, and future prospective have also been discussed in this article.     

Nickel and Ultraviolet-B Stresses Induce Differential Growth and Photosynthetic Responses in Pisum sativum L. Seedlings

Enhanced level of UV-B radiation and heavy metals in irrigated soils due to anthropogenic activities are deteriorating the environmental conditions necessary for growth and development of plants. The present study was undertaken to study the individual and interactive effects of heavy metal nickel (NiCl(2)·6H(2)O; 0.01, 0.1, 1.0?mM) and UV-B exposure (0.4 W m(-2); 45?min corresponds to 1.08 KJ m(-2)) on growth performance and photosynthetic activity of pea (Pisum sativum L.) seedlings. Ni treatment at high doses (0.1 and 1.0?mM Ni) and UV-B alone reduced chlorophyll content and photosynthetic activity (oxygen yield, carbon fixation, photorespiration, and PSI, PSII, and whole chain electron transport activities), and declining trends continued with combined doses. In contrast to this, Ni at 0.01?mM appeared to be stimulatory for photosynthetic pigments and photosynthetic activity, thereby enhanced biomass was observed at this concentration. However, combined dose (UV-B + 0.01?mM Ni) caused inhibitory effects. Carotenoids showed different responses to each stress. Nickel at high doses strongly inhibited PSII activity and the inhibition was further intensified when chloroplasts were simultaneously exposed to UV-B radiation. PSI activity appeared to be more resistant to each stress. High doses of Ni (0.1and 1.0?mM) and UV-B alone interrupted electron flow at the oxygen evolving complex. Similar damaging effects were caused by 0.01 and 0.1?mM Ni together with UV-B, but the damage extended to PSII reaction center in case of 1.0?mM Ni in combination with UV-B. In conclusion, the results demonstrate that low dose of Ni stimulated the growth performance of pea seedlings in contrast to its inhibitory role at high doses. However, UV-B alone and together with low as well as high doses of Ni proved to be toxic for P. sativum L.     

Primary empty sella with isolated ACTH deficiency and microprolactinoma

The empty sella turcica is defined as the herniation of the subarachnoid space within the sella with displacement of the pituitary towards the posteroinferior wall. By autopsy studies, the incidence in the general population is around 20%. The association of prolactinoma and empty sella has been coincidental & infrequently reported. As such for microadenoma, visual field testing and screening for hypopituitarism is not needed, but if it is associated with empty sella, both visual field testing and screening for hypopituitarism is necessary.     

Proteome expression and carbonylation changes during Trypanosoma cruzi infection and Chagas disease in rats

Inflammation and oxidative stress, elicited by Trypanosoma cruzi infection, are important pathologic events during progressive Chagasic cardiomyopathy. In this study, we infected Sprague-Dawley rats with T. cruzi, and treated with phenyl-α-tert-butylnitrone (PBN-antioxidant) and/or benznidazole (BZ-anti-parasite). We employed two-dimensional gel electrophoresis/mass spectrometry to investigate (a) the plasma proteomic changes associated with infection and disease development, and (b) the beneficial effects of PBN and BZ in controlling the disease-associated plasma profile. Matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) tandem MS (MS/MS) analysis of differentially expressed (total 146) and oxidized (total 48) protein spots yielded 92 unique proteins. Our data showed that treatment with PBN and BZ restored the differential expression of 65% and 30% of the disease-associated proteins to normal level, respectively, and PBN prevented development of oxidative adducts on plasma proteins. Western blotting to detect dinitrophenyl-derivatized carbonyl-proteins revealed plasma proteins were maximally oxidized during acute infection. Functional and disease/disorder analyses allocated a majority of the differentially expressed and oxidized proteins into inflammation/immunity and lipid metabolism categories and to molecular pathways associated with heart disease (e.g. cardiac infarction, contractile dysfunction, hypertrophy, and hypertension) in chagasic rats, and to curative pathways (e.g. ROS scavenging capacity, immune regulation) in infected rats treated with PBN and/or BZ. We validated the two-dimensional gel electrophoresis results by Western blotting, and demonstrated that the disease-associated increased expression of gelsolin and vimentin and release of cardiac MYL2 in the plasma of chagasic rats was returned to control level by PBN/BZ treatment. Increased plasma levels of gelsolin, MYL2 and vimentin were directly correlated with the severity of cardiac disease in human chagasic patients. Together, these results demonstrate the plasma oxidative and inflammatory response profile, and plasma detection of cardiac proteins parallels the pathologic events contributing to Chagas disease development, and is of potential utility in diagnosing disease severity and designing suitable therapy for management of human chagasic patients.     

Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011-2050

Background

Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa.

Methods

We model a best case scenario of 90% annual HIV testing coverage in adults 15–49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm³ (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011–2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses.

Results

Expanding ART to CD4 count <350 cells/mm³ prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9–194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%.

Conclusion

Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.     

The Effect of Heart Rate Variability Biofeedback on Performance Psychology of Basketball Players

Coping with pressure and anxiety is an ineluctable demand of sports performance. Heart rate variability (HRV) Biofeedback (BFB) shall be used as a tool for self regulating physiological responses resulting in improved psycho physiological interactions. For further analysis, the present study has been designed to examine the relationship between anxiety and performance and also effectiveness of biofeedback protocol to create stress-eliciting situation in basketball players. Thirty basketball players of university level and above (both male and female) aged 18–28 years, who scored a minimum of 20 in state trait anxiety inventory, were randomly divided into three equal groups- Experimental (Biofeedback) group, Placebo group and Control (No Treatment) group. The BFB group received HRV BFB training for 10 consecutive days for 20 min that included breathing at individual’s resonant frequency through a pacing stimulus; Placebo group was shown motivational video clips for 10 consecutive days for 10 min, whereas No Treatment Control group was not given any intervention. Two way repeated measure ANOVA was applied to analyze the differences within and between the groups. Anxiety, coping self-efficacy, heart rate variability, respiration rate, and performance (dribbling, passing and shooting) at session 1, 10 and 1 month follow up were statistically significant in each group along with interaction of group and time (p < 0.001). Also, all the measures showed statistically significant inter group difference (p < 0.05). The findings are harmonious with existing data on HRV BFB as a strategy for dealing with anxiety. The Placebo group showed improvement in self efficacy and performance post training. The Control group showed no change in any variable except performance. The results of the study support the idea that HRV BFB lowers the anxiety and thus there seems to be a potential association between HRV BFB and performance optimization.