Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice

Objective:The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory.Results:Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded.Conclusion:Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies.KEY WORDS: And bupropion, caffeine, duloxetine, memory     

Design,Synthesis, and Optimization of Balanced Dual NK1/NK3 Receptor Antagonists

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HIV-1 clade-C-associated "ALS"-like disorder: first report from India

A patient of ALS-like disorder in an HIV-1 clade-C-infected heterosexual male is being reported. A 37-year-old gentleman presented with subacute, progressive asymmetrical onset of weakness and wasting of upper limbs associated with brisk muscle stretch reflexes and without any sensory or sphincter involvement. While nerve conduction tests were normal, the EMG of proximal and distal limb muscles on both sides revealed evidence of denervation and reinnervation. Routine blood and urine tests and investigations for underlying causes of motor neuron disease were noncontributory. He was HIV-1, subtype clade C seropositive. A diagnosis of HIV-related anterior horn cell disease was considered and zidovudine, lamivudine and nevirapine were started. After 1 month, there was a subjective improvement of 10% and objective improvement in strength of muscles of proximal upper limb on both sides by one grade power on MRC scale. Reports of amyotrophic lateral sclerosis (ALS)-like illness in HIV are sparse. The reversibility of "ALS"-like features in this subgroup of patients might offer an insight into the pathogenesis of amyotrophic lateral sclerosis. This is a first report of ALS-like illness caused by subtype C of HIV-1 strain.     

HIV-1 Tat-specific IgG antibodies in high-responders target a B-cell epitope in the cysteine-rich domain and block extracellular Tat efficiently

Tat, an important regulatory protein of HIV-1, has been implicated in HIV-related pathogenesis. Immune responses to Tat, although underrepresented, confer protection against disease progression, in natural infection and experimental immunization, making Tat an attractive vaccine candidate. Information on immune responses to Tat from India which has the second largest HIV incidence has been lacking. Here we report a cross-sectional study evaluating the humoral response to Tat from a large number of samples from two southern states of India. 14% of the seropositive (63/447) and 4.6% of seronegative samples (7/150) harbored Tat-reactive antibodies. A significant number of the seropositive samples contained high levels of anti-Tat antibodies (31/447) which demonstrated class-switch to IgG1 and bound to Tat with high avidity. Cross-reactivity analysis showed that these antibodies interacted with Tat from different clades with variable degree withthe highest interaction with subtype-AE and the least with subtype-B Tat. Importantly, a B-cell epitope in the cysteine-rich domain was found to be the most immunodominant one and antibodies interacting with this epitope blocked extracellular Tat efficiently. To the best of our knowledge this is the first report on immune responses to Tat from Indian populations and the data presented here could significantly contribute to HIV Tat vaccine design.     

Vanillic acid derivatives from the green algae Cladophora socialis as potent protein tyrosine phosphatase 1B inhibitors

A novel vanillic acid derivative (1) and its sulfate adduct (2) were isolated from a green algae, Cladophora socialis. The structures of 1 and 2 were elucidated from NMR and HRESIMS experiments. Both compounds showed potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), an enzyme involved in the regulation of insulin cell signaling. Compounds 1 and 2 had IC50 values of 3.7 and 1.7 microM, respectively.     

Niphatoxin C, a cytotoxic tripyridine alkaloid from Callyspongia sp

As part of our studies to discover P2X 7 receptor antagonists, the sponge Callyspongia sp. was investigated. A new tripyridine alkaloid niphatoxin C ( 1) was isolated and had P2X 7 receptor antagonism; however, cytotoxicity of THP-1 cells was the predominant biological effect at higher concentrations. Its structure was determined by 1- and 2-D NMR spectroscopy.     

Retinal nerve fiber layer evaluation of spectral domain optical coherence tomograph and scanning laser polarimeter to diagnose glaucoma

Purpose

To compare the abilities of retinal nerve fiber layer (RNFL) parameters of spectral domain optical coherence tomograph (SDOCT) and scanning laser polarimeter (GDx enhanced corneal compensation; ECC) in detecting glaucoma.

Methods

In a cross-sectional study, 215 eyes of 165 subjects (106 eyes of 79 glaucoma patients and 109 eyes of 86 controls) referred by general ophthalmologists for glaucoma evaluation underwent RNFL imaging with SDOCT and GDx ECC. Ability of RNFL parameters of SDOCT to discriminate glaucoma eyes from control eyes was compared with that of GDx ECC using area under operating characteristic curves (AUCs), sensitivities at fixed specificities, and likelihood ratios (LRs).

Results

AUC of the average RNFL thickness of SDOCT to differentiate glaucoma from control eyes (0.868) was comparable (P=0.32) to that of GDx ECC (0.855). Sensitivity at 95% specificity was 63.2% for average RNFL thickness of SDOCT and 48.1% for the average RNFL measurement of GDx ECC. LRs of outside normal limits category of SDOCT parameters ranged between 5.6 and 7.7 while the same of GDx ECC parameters ranged between 3.1 and 3.7. LRs of within normal limits category of SDOCT parameters ranged between 0.18 and 0.24 while the same of GDx ECC parameters ranged between 0.20 and 0.32.

Conclusion

Though AUCs and sensitivities at fixed specificities were comparable between the RNFL parameters of SDOCT and GDx ECC in diagnosing glaucoma, LRs indicated that the RNFL parameters of SDOCT were better in ‘ruling in'' glaucoma.