Effects of Antagonists and Heat on TRPM8 Channel Currents in Dorsal Root Ganglion Neuron Activated by Nociceptive Cold Stress and Menthol

Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperature and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of environmental cold stress such as cold allodynia in dorsal root ganglion (DRG) neuron; however, the underlying mechanisms of action are unclear. We tested the effects of physiological heat (37°C), anthralic acid (ACA and 0.025 mM), 2-aminoethyl diphenylborinate (2-APB and 0.05) on noxious cold (10°C) and menthol (0.1 mM)-induced TRPM8 cation channel currents in the DRG neurons of rats. DRG neurons were freshly isolated from rats. In whole-cell patch clamp experiments, TRPM8 currents were consistently induced by noxious cold or menthol. TRPM8 channels current densities of the neurons were higher in cold and menthol groups than in control. When the physiological heat is introduced by chamber TRPM8 channel currents were inhibited by the heat. Noxious cold-induced Ca²⁺ gates were blocked by the ACA although menthol-induced TRPM8 currents were not blocked by ACA and 2-APB. In conclusion, the results suggested that activation of TRPM8 either by menthol or nociceptive cold can activate TRPM8 channels although we observed the protective role of heat, ACA and 2-APB through a TRPM8 channel in nociceptive cold-activated DRG neurons. Since cold allodynia is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in DRG neurons.     

In vivo glucose-6-phosphatase inhibitory,toxicity and antidiabetic potentials of 2-picolylamine thioureas in Swiss albino mice

The 2-picolylamine is a simplest analogue of the alkaloid that has secondary and tertiary nitrogen function in its cyclic structure like that of alkaloids that can be derivatized to a number of biologically active compounds. In connection to our previous work, in the present work, three thiourea derivatives (I = 1,3-bis(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl) thiourea, II = 1,3-bis (pyridin-2-ylmethyl) thiourea, and III = 1-(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl)-3-phenylthiourea) were synthesized using 2-picolylamine template which is a readily available synthetic analogue of naturally occurring alkaloid. The biological effect of the synthesized derivatives were monitored on the activity of glucose-6-phosphatase in Swiss albino mice (21-days). The derivatives were also tested for their potential toxicity in a 28-days sub-chronic toxicity studies by assessing their effects on different parameters like hematological, serum biochemistry and liver histology. The therapeutic effect of the safe derivative (I) was examined in streptozotocin-induced diabetic mice as well. The derivatives showed inhibition of the enzyme activity from good to an excellent degree. Compound I had the highest inhibition with 21.42 ± 5.113 mg of the released phosphate as compared to that of the positive control group (84.55 ± 3.213 mg). Only I turned out to be safe for use in animals without exerting any toxic or lethal effects on any of the assessed parameters in the used animal model. Compound I efficiently reversed the effects like hyperglycemia, hyperlipidemia and weight loss in the test animals. Out of these three-tested compounds, I was found safe to be use as therapeutic agent in diabetes complications. However, further toxicological studies in other animal models are needed as well.     

Therapeutic effects of Typha elephantina leave’s extract against paracetamol induced renal injury in rabbits

Present study focuses on ameliorative potential of Typha elephantina leave’s aqueous (TE.AQ) extract against Paracetamol (PCM) induced toxicity in rabbits. We fed the male rabbits with 300 mg PCM in alone and in combination with TE.AQ at different doses i.e. (100, 200 and 300 mg/kg body weight) or silymarin (100 mg/kg) daily for 21 days. PCM in alone significantly (P < 0.5) increased serum urea, uric acid, creatinine, total protein, albumin, globulin and blood urea nitrogen. Serum sodium, potassium and magnesium level were high. The glutathione, radical scavenging activity and Thiobarbituric acid reactive substances were significantly reduced. Treatment with TE.AQ at dose rate 300 mg/kg body weight and Silymarin significantly ameliorated all the parameters when compared with PCM administered group. The 100 and 200 mg of TE.AQ showed no significant effects. The histopathological examination confirmed the therapeutic potential of TE.AQ. These results established the presence of natural antioxidants in Typha elephantina leaves.     

In-vitro and In-vivo management of Meloidogyne incognita (Kofoid and White) Chitwood and Rhizoctonia bataticola (Taub.) Butler in cotton using organic’s

Root-knot nematodes Meloidogyne incognita (Kofoid and White) Chitwood and Rhizoctonia bataticola (Taub.) Butler, fungus, are very dangerous root damaging pathogens. Present study was planned to establish a chemical control of these root deteriorating pathogens under lab conditions as well as in field. Maximum death rate of nematode juveniles and minimum numbers of nematode eggs hatched were recorded in plates treated with Cadusafos (Rugby® 100G) @12 g/100 ml and Cartap® (4% G) @9g/100 ml. Chemical treatment of Rhizoctonia bataticola with Trifloxystrobin + Tebuconazole (Nativo®) @0.2 g/100 ml and Mancozeb + Matalaxyl (Axiom) @0.25 g/100 ml significantly controlled the mycelial growth in plates. The best treatments tested in laboratory were applied in field as protective and curative treatments. Results proved that chemical control of root-knot nematode and root rot fungi by tested chemicals at recommended time and dose is a significant management technique under field conditions.     

Will an Unsupervised Self-Testing Strategy for HIV Work in Health Care Workers of South Africa? A Cross Sectional Pilot Feasibility Study

Background

In South Africa, stigma, discrimination, social visibility and fear of loss of confidentiality impede health facility-based HIV testing. With 50% of adults having ever tested for HIV in their lifetime, private, alternative testing options are urgently needed. Non-invasive, oral self-tests offer a potential for a confidential, unsupervised HIV self-testing option, but global data are limited.

Methods

A pilot cross-sectional study was conducted from January to June 2012 in health care workers based at the University of Cape Town, South Africa. An innovative, unsupervised, self-testing strategy was evaluated for feasibility; defined as completion of self-testing process (i.e., self test conduct, interpretation and linkage). An oral point-of-care HIV test, an Internet and paper-based self-test HIV applications, and mobile phones were synergized to create an unsupervised strategy. Self-tests were additionally confirmed with rapid tests on site and laboratory tests. Of 270 health care workers (18 years and above, of unknown HIV status approached), 251 consented for participation.

Findings

Overall, about 91% participants rated a positive experience with the strategy. Of 251 participants, 126 evaluated the Internet and 125 the paper-based application successfully; completion rate of 99.2%. All sero-positives were linked to treatment (completion rate:100% (95% CI, 66.0–100). About half of sero-negatives were offered counselling on mobile phones; completion rate: 44.6% (95% CI, 38.0–51.0). A majority of participants (78.1%) were females, aged 18–24 years (61.4%). Nine participants were found sero-positive after confirmatory tests (prevalence 3.6% 95% CI, 1.8–6.9). Six of nine positive self-tests were accurately interpreted; sensitivity: 66.7% (95% CI, 30.9–91.0); specificity:100% (95% CI, 98.1–100).

Interpretation

Our unsupervised self-testing strategy was feasible to operationalize in health care workers in South Africa. Linkages were successfully operationalized with mobile phones in all sero-positives and about half of the sero-negatives sought post-test counselling. Controlled trials and implementation research studies are needed before a scale-up is considered.     

Accumulation of Essential and Trace Elements in Guar (Cyamopsis tetragonoloba) and Guar Gum Cultivated in Semi-arid Regions of Sindh,Pakistan

Biological Trace Element Research - For physiological and biochemical studies, it is considered essential to have knowledge about the accumulation of mineral elements in plants and their...     

Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects

The liver is considered a radiosensitive organ. However, in rats, high single-dose irradiation (HDI) showed only mild effects. Consequences of fractionated irradiation (FI) in such an animal model have not been studied so far. Rats were exposed to selective liver FI (total dose 60 Gy, 2 Gy/day) or HDI (25 Gy) and were killed three months after the end of irradiation. To study acute effects, HDI-treated rats were additionally killed at several time points between 1 and 48 h. Three months after irradiation, no differences between FI and HDI treatment were found for macroscopically detectable small “scars” on the liver surface and for an increased number of neutrophil granulocytes distributed in the portal fields and through the liver parenchyma. As well, no changes in HE-stained tissues or clear signs of fibrosis were found around the portal vessels. Differences were seen for the number of bile ducts being increased in FI- but not in HDI-treated livers. Serum levels indicative of liver damage were determined for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (γGT) and lactate dehydrogenase (LDH). A significant increase of AP was detected only after FI while HDI led to the significant increases of AST and LDH serum levels. By performing RT-PCR, we detected up-regulation of matrix metalloproteinases, MMP-2, MMP-9, MMP-14, and of their inhibitors, TIMP-1, TIMP-2 and TIMP-3, shortly after HDI, but not at 3 month after FI or HDI. Overall, we saw punctual differences after FI and HDI, and a diffuse formation of small scars at the liver surface. Lack of “provisional clot”-formation and absence of recruitment of mononuclear phagocytes could be one explanation for scar formation as incomplete repair response to irradiation.     

The c.42_52del11 Mutation in TPRN and Progressive Hearing Loss in a Family from Pakistan

The DFNB79 locus harbors TPRN mutations in which have been reported in a few families with deafness. Four frameshift mutations in TPRN have been described to cause severe or severe-to-profound hearing loss in Moroccan and Pakistani families, and a single frameshift mutation was associated with progressive hearing loss in deaf individuals in a Dutch family. We identified a Pakistani family in which the affected individuals were homozygous for a pathogenic mutation, c.42_52del11, in TPRN (p.G15Afs150X). In contrast to the previously reported individuals affected by the same mutation, hearing loss is likely to be progressive in this family. Thus the same mutation of TPRN can be associated with different thresholds of hearing as well as differences in the stability of the phenotype.