Effects of TRPV1 activation on synaptic excitation in the dentate gyrus of a mouse model of temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is a condition characterized by an imbalance between excitation and inhibition in the temporal lobe. Hallmarks of this change are axon sprouting and accompanying synaptic reorganization in the temporal lobe. Synthetic and endogenous cannabinoids have variable therapeutic potential in treating intractable temporal lobe epilepsy, in part because cannabinoid ligands can bind multiple receptor types. This study utilized in vitro electrophysiological methods to examine the effect of transient receptor potential vanilloid type 1 (TRPV1) activation in dentate gyrus granule cells in a murine model of TLE. Capsaicin, a selective TRPV1 agonist had no measurable effect on overall synaptic input to granule cells in control animals, but significantly enhanced spontaneous and miniature EPSC frequency in mice with TLE. Exogenous application of anandamide, an endogenous cannabinoid that acts at both TRPV1 and cannabinoid type 1 receptors (CB1R), also enhanced glutamate release in the presence of a CB1R antagonist. Anandamide reduced the EPSC frequency when TRPV1 were blocked with capsazepine. Western blot analysis of TRPV1 receptor indicated protein expression was significantly greater in the dentate gyrus of mice with TLE compared with control mice. This study indicates that a prominent cannabinoid agonist can increase excitatory circuit activity in the synaptically reorganized dentate gyrus of mice with TLE by activating TRPV1 receptors, and suggests caution in designing anticonvulsant therapy based on modulating the endocannabinoid system.     

Pure neuritic leprosy in India: an appraisal

BACKGROUND: Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature. OBJECTIVE: To study the epidemiological characteristics of PNL in India. MATERIALS AND METHODS: A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis. RESULTS: Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period. CONCLUSION: PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.     

Copper nanoparticles anchored onto boron-doped graphene nanosheets for use as a high performance asymmetric solid-state supercapacitor

There is a high demand for high energy and power density in the field of energy storage devices. To rectify these limitations, a novel asymmetric solid-state supercapacitor (ASSC) was designed and fabricated using a copper anchored boron doped graphene nanosheet (CuBG) as a negative electrode and reduced graphene nanoplatelets as a positive electrode with H₂SO₄/PVA as the quasi-solid electrolyte. The CuBG was prepared using a two step hydrothermal process followed by pyrolysis at different temperatures using chemical vapour deposition (CVD), using copper sulphate (CuSO₄) and boron-trioxide (B₂O₃) as precursors, for doping in graphene oxide. Owing to the remarkable structure and morphology of Cu nanoparticles on nanosheets of boron intercalated with graphene oxide, the nanosheets exhibit a high specific capacitance of 483 Fg⁻¹ at 1 Ag⁻¹ with a capacitance retention of 96% after 5000 cycles, respectively, in a two-electrode system. In addition, the designed and fabricated solid state ASSC device of rGO//CuBG exhibited a high energy and power density of 132.5 W h kg⁻¹ and 1000 W kg⁻¹, respectively, in a wide potential window of 2.0 V, with an excellent stability, retaining 91% of its initial specific capacitance after 5000 cycles. The electrochemical capacitance of CuBG was also evaluated in a three and two electrode system using a KOH and KOH/PVA solid electrolyte respectively. A specific capacitance of 87.5 Fg⁻¹ was achieved at 1 Ag⁻¹ using the fabricated asymmetric device with a 31.1 W h kg⁻¹ energy density at a corresponding power density of 800 W kg⁻¹ and an 85% capacitance was retained after 5000 cycles. The kinetics of the interfacial charge transport phenomena were analysed using a Nyquist plot of the electrochemical impedance analysis.

There is a high demand for high energy and power density in the field of energy storage devices.     

Aliovalent-doped sodium chromium oxide (Na0.9Cr0.9Sn0.1O2 and Na0.8Cr0.9Sb0.1O2) for sodium-ion battery cathodes with high-voltage characteristics

NaCrO₂ with high rate-capability is an attractive cathode material for sodium-ion batteries (NIBs). However, the amount of reversibly extractable Na⁺ ions is restricted by half, which results in relatively low energy density for practical NIB cathodes. Herein, we describe aliovalent-doped O3–Na_0.9[Cr_0.9Sn_0.1]O₂ (NCSnO) and O3–Na_0.8[Cr_0.9Sb_0.1]O₂ (NCSbO), both of which show high-voltage characteristics that translate to an increase in energy density. In contrast to NaCrO₂, NCSnO and NCSbO can be reversibly charged to 3.80 and 3.95 V, respectively, delivering 0.5 Na⁺ along with Cr^3+/4+ redox alone. The reversible chargeability to Na_0.4[Cr_0.9Sn_0.1]O₂ and Na_0.3[Cr_0.9Sb_0.1]O₂ is not associated with the suppression of Cr⁶⁺ formation. Both compounds show concentrations of Cr⁶⁺ that are higher than that of Na_0.3CrO₂, with an absence of O3′ phases. This implies that aliovalent-doping contributes to a suppression of the Cr⁶⁺ migration into tetrahedral sites in the interslab space, which reduces the possibility of irreversible comproportionation. NCSnO and NCSbO deliver capacities comparable to that of NaCrO₂, but show a higher average discharge voltage (2.94 V for NaCrO₂; 3.14 V for NCSnO; 3.21 V for NCSbO), which leads to a noticeable increase in energy densities. The high-voltage characteristics of NCSnO and NCSbO are also validated via density-functional-theory calculations.

In contrast to O3–NaCrO₂, O3–Na_0.8[Cr_0.9Sb_0.1]O₂ shows reversibility when charged to 3.95 V and high-voltage charge/discharge features, which results in improvement of energy density.     

Overexpression of sarcolipin decreases myocyte contractility and calcium transient

OBJECTIVE: Sarcolipin (SLN) is a novel 31-amino-acid protein associated with the sarcoplasmic reticulum (SR) whose function in cardiac muscle is poorly defined. In this study, we tested the hypothesis that SLN is a regulator of SR Ca(2+) transport function by overexpressing SLN in adult rat ventricular myocytes which express low levels of SLN. METHODS: Expression of SLN mRNA in rat tissues was analyzed by Northern blot as well by RT-PCR analysis. To define the role of SLN in cardiac muscle contractility, we overexpressed SLN in adult rat ventricular myocytes using adenoviral gene transfer techniques. Localization of SLN in the adult rat ventricular myocytes was determined using confocal microscopy. Myocyte contractility and calcium transients were measured using edge detection and Fura 2AM. RESULTS: Our results demonstrate that overexpression of SLN decreased the cell shortening significantly when compared to control myocytes, whereas the time to peak contraction was not altered. In addition, SLN overexpression prolonged the time of 50% relaxation. Calcium transient analysis shows that time to 50% decay of [Ca(2+) ]i was markedly prolonged in SLN-overexpressing myocytes (control -245.0+/-3.78 vs. SLN -199.0+/-3.25 ms, p<0.001). However, there were no significant differences in peak amplitudes of [Ca(2+)](i) between SLN-overexpressing and control myocytes. We further demonstrate that SLN is localized within the SR membrane similar to PLB and SR Ca(2+) ATPase. Co-immunoprecipitation studies indicate that SLN can physically interact with phospholamban. CONCLUSIONS: We conclude that SLN may play an important role in regulating the SR calcium ATPase pump, possibly by interacting with phospholamban.     

Accidental colchicine overdose. A case report and literature review

Colchicine overdose is uncommon but potentially life threatening. It is a safe drug when used according to established therapeutic guidelines but causes serious systemic effects if ingested in doses that exceed the recommendations. Overdose must therefore be recognised early and treated appropriately to optimise the outcome. A fatal case of colchicine overdose caused by inappropriate self medication is reported and to the best of the authors' knowledge, there has been no report of fatal accidental overdose in the United Kingdom. The pharmacology of colchicine, the clinical features associated with overdose, and the options for treatment are discussed.     

Glycosylated neuropeptides: A new vista for neuropsychopharmacology?

The application of endogenous neuropeptides (e.g., enkephalins) as analgesics has been retarded by their poor stability in vivo and by their inability to effectively penetrate the blood-brain barrier (BBB). Effective BBB transport of glycosylated enkephalins has been demonstrated in several labs now. Analgesia (antinociception) levels greater than morphine, and with reduced side effects have been observed for several glycopeptides related to enkephalin. Somewhat paradoxically, enhanced BBB transport across this lipophilic barrier is achieved by attaching water-soluble carbohydrate groups to the peptide moieties to produce biousian glycopeptides that can be either water-soluble or membrane bound. Transport is believed to rely on an endocytotic mechanism (transcytosis), and allows for systemic delivery and transport of the water-soluble glycopeptides. Much larger endorphin/dynorphin glycopeptide analogs bearing amphipathic helix address regions also have been shown to penetrate the BBB in mice. This holds forth the possibility of transporting much larger neuropeptides across the BBB, which may encompass a wide variety of receptors beyond the opioid receptors.