6-Methoxyflavone antagonizes chronic constriction injury and diabetes associated neuropathic nociception expression.

Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects.

Motor dysfunction of the gut in Duchenne muscular dystrophy: A review.

BACKGROUND: Duchenne's muscular dystrophy (DMD) is a severe type of hereditary, neuromuscular disorder caused by a mutation in the dystrophin gene resulting in the absence or production of truncated dystrophin protein. Conventionally, clinical descriptions of the disorder focus principally on striated muscle defects; however, DMD manifestations involving gastrointestinal (GI) smooth muscle have been reported, even if not rigorously studied. PURPOSE: The objective of the present review is to offer a comprehensive perspective on the existing knowledge concerning GI manifestations in DMD, focusing the attention on evidence in DMD patients and mdx mice. This includes an assessment of symptomatology, etiological pathways, and potential corrective approaches. This paper could provide helpful information about DMD gastrointestinal implications that could serve as a valuable orientation for prospective research endeavors in this field. This manuscript emphasizes the effectiveness of mdx mice, a DMD animal model, in unraveling mechanistic insights and exploring the pathological alterations in the GI tract. The gastrointestinal consequences evident in patients with DMD and the mdx mice models are a significant area of focus for researchers. The exploration of this area in depth could facilitate the development of more efficient therapeutic approaches and improve the well-being of individuals impacted by the condition.

A Novel Monopole Ultra-Wide-Band Multiple-Input Multiple-Output Antenna with Triple-Notched Characteristics for Enhanced Wireless Communication and Portable Systems.

This study introduces a monopole 4 × 4 Ultra-Wide-Band (UWB) Multiple-Input Multiple-Output (MIMO) antenna system with a novel structure and outstanding performance. The proposed design has triple-notched characteristics due to CSRR etching and a C-shaped curve. The notching occurs in 4.5 GHz, 5.5 GHz, and 8.8 GHz frequencies in the C-band, WLAN band, and satellite network, respectively. Complementary Split-Ring Resonators (CSRR) are etched at the feed line and ground plane, and a C-shaped curve is used to reduce interference between the ultra-wide band and narrowband. The mutual coupling of CSRR enables the MIMO architecture to achieve high isolation and polarisation diversity. With prototype dimensions of (60.4 × 60.4) mm2, the proposed antenna design is small. The simulated and measured results show good agreement, indicating the effectiveness of the UWB-MIMO antenna for wireless communication and portable systems.

Targeting Anti-Inflammatory Pathways to Treat Diabetes-Induced Neuropathy by 6-Hydroxyflavanone.

It is evident that inflammation and metabolic syndrome instigated by diabetes mellitus can precipitate diabetes-induced neuropathy (DIN) and pain. In order to find an effective therapeutic method for diabetes-related problems, a multi-target-directed ligand model was used. 6-Hydroxyflavanone (6-HF) carrying anti-inflammatory and anti-neuropathic pain potential due to its quadruplicate mechanisms, targeting cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and opioid and GABA-A receptors was investigated. The anti-inflammatory potential of the test drug was confirmed utilizing in silico, in vitro, and in vivo tests. A molecular simulation approach was utilized to observe the interaction of 6-HF with the inflammatory enzyme COX-2 as well as opioid and GABA-A receptors. The same was confirmed via in vitro COX-2 and 5-LOX inhibitory assays. In vivo tests were performed to analyze the thermal anti-nociception in the hot-plate analgesiometer and anti-inflammatory action in the carrageenan-induced paw edema model in rodents. The potential anti-nociceptive effect of 6-HF was evaluated in the DIN model in rats. The Naloxone and Pentylenetetrazole (PTZ) antagonists were used to confirm the underlying mechanism of 6-HF. The molecular modeling studies revealed a favorable interaction of 6-HF with the identified protein molecules. In vitro inhibitory studies revealed that 6-HF inhibited the COX-2 and 5-LOX enzymes significantly. The 6-HF at dosages of 15, 30, and 60 mg/kg substantially reduced heat nociception in a hot plate analgesiometer as well as carrageenan-induced paw edema in rodent models. The authors discovered that 6-HF had anti-nociception properties in a streptozotocin-induced diabetic neuropathy model. According to the findings of this study, 6-HF was demonstrated to diminish inflammation caused by diabetes as well as its anti-nociception effect in DIN.

A Miniaturized Arc Shaped Near Isotropic Self-Complementary Antenna for Spectrum Sensing Applications.

This paper presents the design of an arc-shaped near-isotropic self-complementary antenna for spectrum sensing application. An arc-shaped dipole with horizontal and vertical arms is used to achieve a near isotropic radiation pattern. The radiation pattern improved by adjusting the horizontal and vertical arm lengths. Simulated and experimental results show that the proposed antenna has an impedance bandwidth of 146% (2.4-18.4 GHz) for VSWR ≤ 2 with a good radiation pattern. In order to quantify the antenna performance, antenna gain variation, bandwidth, efficiency, and size have been compared with previously reported designs. It is shown that the proposed arc-shaped antenna can achieve nearly isotropic radiation patterns with a maximum radiation efficiency of 92%. The isotropic performance of the antenna has been characterized by observing the radiation pattern and solid angle. The FR4 substrate is used as a dielectric with relative permittivity 4.4 and loss tangent of 0.02. (εr = 4.4, h = 1.6 mm) The simulated and measured results are in good comparison, and the proposed design is a suitable candidate for spectrum sensing.

Phytotherapeutic Approach in the Management of Cisplatin Induced Vomiting; Neurochemical Considerations in Pigeon Vomit Model.

Cisplatin induced vomiting involves multiple mechanisms in its genesis and a single antiemetic agent do not cover both the phases (acute & delayed) of vomiting in clinics; necessitating the use of antiemetics in combination. Cannabis sativa and other selected plants have ethnopharmacological significance in relieving emesis. The aim of the present study was to investigate the intrinsic antiemetic profile of Cannabis sativa (CS), Bacopa monniera (BM, family Scrophulariaceae), and Zingiber officinale (ZO, family Zingiberaceae) in combinations against vomiting induced by highly emetogenic anticancer drug-cisplatin in pigeons. We have analysed the neurotransmitters which trigger the vomiting response centrally and peripherally. Electrochemical detector (ECD) was used for the quantification of neurotransmitters and their respective metabolites by high performance liquid chromatography in the brain stem (BS) and area postrema (AP) while peripherally in the small intestine. Cisplatin (7 mg/kg i.v.) induced reliable vomiting throughout the observation period (24 hrs). CS-HexFr (10 mg) + BM-MetFr (10 mg)-Combination 1, BM-ButFr (5 mg) + ZO-ActFr (25 mg)-Combination 2, ZO-ActFr (25 mg) + CS-HexFr (10 mg)-Combination 3, and CS-HexFr (10 mg) + BM-ButFr (5 mg)-Combination 4; provided ~30% (30 ± 1.1), 70% (12 ± 0.4; P < 0.01), 60% (19 ± 0.2; P < 0.05) and 90% (05 ± 0.1; P < 0.001) protection, respectively, against cisplatin induced vomiting as compared to cisplatin control. Standard MCP (30 mg) provided ~50% (23 ± 0.3) protection (P > 0.05). CS Hexane fraction (10 mg/kg), BM methanolic (10 mg/kg) and bacoside rich n-butanol fraction (5 mg/kg) and ZO acetone fraction (25 mg/kg) alone provided ~62%, 36%, 71%, and 44% protection, respectively, as compared to cisplatin control. The most effective and synergistic combination 4 was found to reduce 5HT and 5HIAA (P < 0.05-0.001) in all the brain areas area postrema (AP)+brain stem (BS) and intestine at the 3rd hour of cisplatin administration. In continuation, at the 18th of cisplatin administration reduction in dopamine (P < 0.001) in the AP and 5HT in the brain stem and intestine (P < 0.001) was observed. The said combination did not change the neurotransmitters basal levels and their respective metabolites any significantly. In conclusion, all the tested combinations offered protection against cisplatin induced vomiting to variable degrees, where combination 4 provided enhanced attenuation by antiserotonergic mechanism at the 3rd hour while a blended antidopaminergic and antiserotonergic mechanism at the 18th hour after cisplatin administration.

Cancerous Tumor Controlled Treatment Using Search Heuristic (GA)-Based Sliding Mode and Synergetic Controller.

Cancerous tumor cells divide uncontrollably, which results in either tumor or harm to the immune system of the body. Due to the destructive effects of chemotherapy, optimal medications are needed. Therefore, possible treatment methods should be controlled to maintain the constant/continuous dose for affecting the spreading of cancerous tumor cells. Rapid growth of cells is classified into primary and secondary types. In giving a proper response, the immune system plays an important role. This is considered a natural process while fighting against tumors. In recent days, achieving a better method to treat tumors is the prime focus of researchers. Mathematical modeling of tumors uses combined immune, vaccine, and chemotherapies to check performance stability. In this research paper, mathematical modeling is utilized with reference to cancerous tumor growth, the immune system, and normal cells, which are directly affected by the process of chemotherapy. This paper presents novel techniques, which include Bernstein polynomial (BSP) with genetic algorithm (GA), sliding mode controller (SMC), and synergetic control (SC), for giving a possible solution to the cancerous tumor cells (CCs) model. Through GA, random population is generated to evaluate fitness. SMC is used for the continuous exponential dose of chemotherapy to reduce CCs in about forty-five days. In addition, error function consists of five cases that include normal cells (NCs), immune cells (ICs), CCs, and chemotherapy. Furthermore, the drug control process is explained in all the cases. In simulation results, utilizing SC has completely eliminated CCs in nearly five days. The proposed approach reduces CCs as early as possible.

Fixed Dose Combination Tablets of Aripiprazole and Divalproex Sodium: a Pilot Pharmacokinetic Study in Human Volunteers.

A combination product of aripiprazole (antipsychotic) and divalproex sodium (mood stabilizer) was recently developed to establish their tolerability and safety in fixed dose combination (FDC). A pilot pharmacokinetic (PK) open-labeled parallel study on healthy human volunteers was carried out to assess the PK of FDC of aripiprazole/divalproex sodium in comparison with its individual components with a view to rationalize therapeutic regimen and potentially improve compliance of bipolar patients in future. A total of 24 volunteers were randomized to aripiprazole 5mg, divalproex sodium 500mg, and FDC (aripiprazole/divalproex sodium 5/500 mg) enteric-coated tablets. Peak plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax) of aripiprazole increased, Cmax of valproic acid increased, and Tmax decreased. Half-life (t1/2) of both aripiprazole and valproic acid decreased. Area under the curve (AUC) of both aripiprazole and valproic acid increased while volume of distribution (Vd) and clearance (Cl) decreased when used in fixed combination. Increase in the AUC and decrease in the Vd of aripiprazole in the presence of valproic acid were found statistically significant while rest of the parameters were insignificant at level 0.05. Although not adequately powered, this pilot study gives an idea that FDC of aripiprazole and divalproex sodium has a PK profile comparable to its mono-component products. Thus, concomitant use of aripiprazole and valproate in FDC is possible which may prove to be a cost-effective and result-oriented substitute for conventional individual tablets to improve patients' compliance; however, further evaluation with positive control is required.

The 7-Hydroxyflavone attenuates chemotherapy-induced neuropathic pain by targeting inflammatory pathway.

Vincristine and paclitaxel are widely used chemotherapeutic drugs for the treatment of brain tumors, breast cancer, leukemia, lymphomas, and malignant solid tumors. Though, these drugs are associated with some severe adverse effects including peripheral neuropathic pain. The anti-nociceptive and anti-inflammatory properties of the 7-Hydroxyflavone (7HF) were evaluated in the mice using thermally- and chemically-induced nociception, naloxone antagonistic test, and carrageenan-induced paw edema models. Initially, the in-vitro cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitory assays were carried out. Peripheral neuropathic pain was induced in the Sprague Dawley (SD) rats by administration of paclitaxel (4 mg/kg) and vincristine (200 µg/kg) on days 1, 3, 5, 7, and 9, respectively. The protective effect of 7HF was assessed against the chemotherapy-induced peripheral neuropathy in the rats. Moreover, the expression of the inflammatory mediators in the spinal cord was investigated through RT-PCR. In addition, a computational study was performed to find the potential therapeutic targets and the binding mechanism of 7HF. The 7HF caused concentration-dependent inhibition of COX-2 and 5-LOX, it attenuated the nociceptive pain, carrageenan-induced paw edema, and the development of mechanical and cold allodynia, and hyperalgesia dose-dependently without causing motor coordination deficit. Likewise, the 7HF decreased the vincristine-induced increased expression of different inflammatory mediators including COX-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and nuclear factor-kappa B (NF-κB). The computational study showed the effective interactions of 7HF with the binding sites of NF-κB, COX-2, and 5-LOX, exert its inhibitory activities. These findings reveal that the 7HF has anti-nociceptive, anti-inflammatory, and anti-neuropathic potentials.

Clinical Investigation on the Impact of Cannabis Abuse on Thyroid Hormones and Associated Psychiatric Manifestations in the Male Population.

Cannabis abuse is a common public health issue and may lead to considerable adverse effects. Along with other effects, the dependence on cannabis consumption is a serious problem which has significant consequences on biochemical and clinical symptoms. This study intends to evaluate the harmful effects of the use of cannabis on thyroid hormonal levels, cardiovascular indicators, and psychotic symptoms in the included patients. This prospective multicenter study was conducted on cannabis-dependent patients with psychotic symptoms (n = 40) vs. healthy control subjects (n = 40). All participants were evaluated for psychiatric, biochemical, and cardiovascular physiological effects. Patients were selected through Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and urine samples, exclusively for the evaluation of cannabis presence. Serum thyroid stimulating hormone (TSH), T3, and T4 levels were measured using the immunoassay technique. Patients were assessed for severity of depressive, schizophrenic, and manic symptoms using international ranking scales. Various quantifiable factors were also measured for the development of tolerance by cannabis. Among the patients of cannabis abuse, 47.5% were found with schizophrenia, 20% with schizoaffective symptoms, 10% with manic symptoms, and 22.5% with both manic and psychotic symptoms. In the group-group and within-group statistical analysis, the results of thyroid hormones and cardiovascular parameters were non-significant. The psychiatric assessment has shown highly significant (p < 0.001) difference of positive, negative, general psychopathology, and total scores [through Positive and Negative Syndrome Scale (PANSS) rating scales] in patients vs. the healthy control subjects. The study revealed that cannabis abuse did not significantly alter thyroid hormones and cardiovascular parameters due to the development of tolerance. However, the cannabis abuse might have a significant contributing role in the positive, negative, and manic symptoms in different psychiatric disorders.

Attenuation of spatial memory in 5xFAD mice by targeting cholinesterases, oxidative stress and inflammatory signaling using 2-(hydroxyl-(2-nitrophenyl)methyl)cyclopentanone.

Alzheimer's disease (AD) is classified pathologically as a progressive neurological disorder associated with memory decline. The study was designed to assess the underlying molecular signaling involved in the neuroprotective effect of the 2-(hydroxyl-(2-nitrophenyl)methyl)cyclopentanone (2NCP) as a novel therapeutic agent for AD. In this connection, in vitro cholinesterases inhibitory and antioxidant activities were investigated. In vivo studies were carried out on a well-known 5xFAD mice model in different behavioural models such as light/dark box,balance beam, rotarod, elevated plus maze (EPM),novel object recognition (NOR), paddling Y-maze, and Morris water maze (MWM) tests. Hippocampus (HC) and frontal cortex (FC) homogenates were examined for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals, glutathione S-transferase (GST), glutathione (GSH), and catalase. Further, we examined the expression of inflammatory cytokines and Nrf2 in the HC and FC through RT-PCR. Computational studies were conducted to predict the binding mode of the 2NCP with target sites of nuclear factor-κB (NF-κB) and cholinesterases. The findings of in vitro assays revealed that the IC50 values of the 2NCP against AChE and BChE were 17 and 23 µg/ml respectively. DPPH antioxidant assay displayed an IC50 value for the 2NCP was 62 µg/ml. Whereas, theex vivo study depicted that the activities of AChE and BChEwere significantly reduced. Moreover, free radicals load, GSH level, catalase and GST activities were significantly declined. Furthermore, in vivostudies showed that the 2NCP treated animals exhibited gradual memory improvement and improved motor functions. RT-PCR study revealed that mRNA levels of the inflammatory mediators (IL-1ß, IL-6, TNF-α) were significantly reduced, while the expression of antioxidant Nrf2 was significantly increased.The molecular docking studies further confirmed that the 2NCP showed excellent binding affinities for NF-κB and cholinesterases. Taken together, the 2NCP improves spatial memory and learning, short- and long-term memory,markedly inhibits cholinesterases, reduced neuroinflammation, and mitigated oxidative stress in the 5xFAD mice; hence the 2NCP may be a potential candidate for the management of AD.

Pharmacological evaluation of the gabapentin salicylaldehyde derivative, gabapentsal, against tonic and phasic pain models, inflammation, and pyrexia.

Gabapentinoids are effective drugs in most animal models of pain and inflammation with variable effects in humans. The current study evaluated the pharmacological activity of gabapentin (GBP) and its salicylaldehyde derivative (gabapentsal; [2-(1-(((2-hydroxybenzylidene) amino) methyl) cyclohexyl) acetic acid]; GPS) in well-established mouse models of nociceptive pain, inflammatory edema, and pyrexia at doses of 25-100 mg/kg. GPS allayed tonic visceral pain as reflected by acetic acid-induced nociception and it also diminished thermally induced nociception as a mimic of phasic thermal pain. Antagonism of GPS-induced antinociceptive activities by naloxone (NLX, 1.0 mg/kg, subcutaneously, s.c), beta-funaltrexamine (ß-FNT, 5.0 mg/kg, s.c), naltrindole (NT, 1.0 mg/kg, s.c), and nor-binaltorphimine (NOR-BNI, 5.0 mg/kg, s.c), and pentylenetetrazole (PTZ-15 mg/kg, intraperitoneally, i.p) implicated an involvement of both opioidergic and GABAergic mechanisms. Tail immersion test was conducted in order to delineate the mechanistic insights of antinociceptive response. Inflammatory edema induced by carrageenan, histamine, or serotonin was also effectively reversed by GPS in a fashion analogous to aspirin (150 mg/kg, i.p), chlorpheniramine (1.0 mg/kg, i.p), and mianserin (1.0 mg/kg, i.p), respectively. Additionally, yeast-induced pyrexia was decreased by GPS in a comparable manner to acetaminophen (50 mg/kg, i.p). These observations suggest that GPS possesses ameliorative properties in tonic, phasic, and tail immersion tests of nociception via opioidergic and GABAergic mechanisms, curbs inflammatory edema, and is antipyretic in nature.

A novel gabapentin analogue assuages neuropathic pain response in chronic sciatic nerve constriction model in rats.

Gabapentin (GBP) is an established drug that has been used in the management of symptoms of neuropathy but it is associated with unwanted side effects such as sedation and motor incoordination. The goal of the study was to find out a drug with greater efficacy and safety for the treatment of neuropathic pain. Our previously synthesized GABA analogue (Gabapentsal, GPS) was tested (25-100 mg/kg, i.p) in chronic constriction injury (CCI) induced nociceptive model of static allodynia, dynamic allodynia, thermal hyperalgesia, mechanical hyperalgesia and cold allodynia in rats (Sprague Dawley). Open field and rotarod tests were performed to assess the impact of GPS on the motor performance of the animals. GBP (100 mg/kg, i.p) was used as a standard for comparison. GPS dose dependently reduced static (P <0.001) and dynamic allodynia (P <0.001), thermal hyperalgesia (P <0.001), mechanical hyperalgesia (P < 0.001) and cold allodynia (P < 0.001). In comparison to GBP, GPS failed to alter any significantly the motor performance of rats in both the open field and rotarod assays. These results suggest that GPS is effective in alleviating nociception in CCI neuropathic pain model but free from the side effect of motor discoordination seen in the treatment with GBP. In conclusion, GPS may prove to be a prospectively more effective and safer option in the management of neuropathic syndromes.

Attenuation of nociceptive and paclitaxel-induced neuropathic pain by targeting inflammatory, CGRP and substance P signaling using 3-Hydroxyflavone.

Paclitaxel is an anti-microtubule agent, most widely used chemotherapeutic agent for the treatment of malignant solid tumors. However, it is associated with some severe side effects including painful neurotoxicity with reporting of neuropathic pain and sensory abnormalities by patients during and after paclitaxel therapy. Peripheral neuropathy was induced by the administration of paclitaxel (4 mg/kg on days 1, 3, 5, and 7). In this study, the anti-nociceptive and anti-inflammatory propensity of 3-Hydroxyflavone (3HF) in mice and the preventive effect of 3HF against paclitaxel-induced peripheral neuropathy in Sprague Dawley (SD) rats were investigated. Moreover, tactile and cold allodynia, thermal and tail immersion hyperalgesia, and effects on motor-coordination were also evaluated. Furthermore, the expression of proinflammatory cytokines i.e. Calcitonin gene-related peptide (CGRP), and Substance P from the spinal cord was examined through RT-PCR. Additionally, a computational structural biology approach was applied to search the potential therapeutic targets and to predict the binding mechanism of 3HF. Treatment of 3HF alleviated the nociceptive pain, paw edema, development of tactile and cold allodynia, and hyperalgesia. Similarly, treatment with 3HF suppressed the paclitaxel-induced increase in mRNA expression of several inflammatory cytokines including tumor necrosis factor -α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), CGRP, and Substance P. However, the daily treatment of 3HF did not affect the motor behaviors of rats. The inhibitory mechanism of 3HF in neuropathic pain is predicted with extensive computational bioinformatics approach which indicates that the 3HF effectively interacts with the binding domains of Nuclear factor-kappa B (NF-κB), CGRP receptor and the receptor of Substance P to exert its inhibitory activities. However, the computationally predicted binding affinities revealed that the potential of binding of the compound with Substance P receptor (Neurokinin 1 receptor) is higher than the other receptors; there NK1R could be the most possible binding target of 3HF. These findings indicate that 3HF has anti-nociceptive, anti-inflammatory, and anti-neuropathic pain effects against paclitaxel-induced neuropathic pain.

The antioxidant N-(2-mercaptopropionyl)-glycine (tiopronin) attenuates expression of neuropathic allodynia and hyperalgesia.

The current pharmacotherapy of neuropathic pain is inadequate as neuropathic pain involves varied clinical manifestations with multifactorial etiology, modulated by a cascade of physical and molecular events leading to different clinical presentations of pain. There is an accumulating evidence of the involvement of oxidative stress in neuropathy, and antioxidants have shown promise in mitigating neuropathic pain syndromes. To explore the evidence supporting this beneficial proclivity of antioxidants, this study investigated the antinociceptive effectiveness of N-(2-mercaptopropionyl)glycine or tiopronin, a well-recognized aminothiol antioxidant, in a refined chronic constriction injury (CCI) rat model of neuropathic pain. Tiopronin (10, 30, and 90 mg/kg, i.p.) and pregabalin (30 mg/kg, i.p.) were administered daily after CCI surgery. The neuropathic paradigms of mechanical/cold allodynia and mechanical/heat hyperalgesia were assessed on days 3, 7, 14, and 21 post-nerve ligation. At the end of study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were estimated in the sciatic nerve, dorsal root ganglion, and spinal cord for assessing the extent of oxidative stress. The expression of neuropathic nociception was attenuated by tiopronin which was observed as a significant attenuation of CCI-induced allodynia and hyperalgesia. Tiopronin reversed the neuronal oxidative stress by significantly reducing MDA, and increasing SOD, CAT, and GSH levels. Pregabalin also showed similar beneficial propensity on CCI-induced neuropathic aberrations. These findings suggest prospective neuropathic pain attenuating efficacy of tiopronin and further corroborated the notion that antioxidants are effective in mitigating the development and expression of neuropathic pain and underlying neuronal oxidative stress.

Analgesic and Antiallodynic Effects of 4-Fluoro-N-(4-Sulfamoylbenzyl) Benzene Sulfonamide in a Murine Model of Pain.

INTRODUCTION: Physical, chemical, thermal injuries along with infectious diseases lead to acute pain with associated inflammation, being the primary cause of hospital visits. Moreover, neuropathic pain associated with diabetes is a serious chronic disease leading to high morbidity and poor quality of life. OBJECTIVE: Earlier multiple sulphonamides have been reported to have an antinociceptive and antiallodynic profile. 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide (4-FBS), a synthetic sulfonamide with reported carbonic anhydrase inhibitory activity, was investigated for its potential effects in mice model of acute and diabetic neuropathic pain. METHODS AND RESULTS: 4-FBS was given orally (p.o.) one hour before the test and then mice were screened for antinociceptive activity by using the tail immersion test, which showed significant antinociceptive effect at both 20 and 40 mg/kg doses. To explore the possible mechanisms, thermal analgesia of 4-FBS was reversed by the 5HT3 antagonist ondansetron 1mg/kg intraperitoneally (i.p.) and by the µ receptor antagonist naloxone (1 mg/kg i.p.), implying possible involvement of serotonergic and opioidergic pathways in the analgesic effect of 4-FBS. Diabetes was induced in mice by a single dose of streptozotocin (STZ) 200 mg/kg i.p. After two weeks, animals first became hyperalgesic and progressively allodynic in the fourth week, which was evaluated through behavioral parameters like thermal and mechanical tests. 4-FBS at 20 and 40 mg/kg p.o. significantly reversed diabetes-induced hyperalgesia and allodynia at 30, 60, 90, and 120 minutes. CONCLUSION: These findings are significant and promising while further studies are warranted to explore the exact molecular mechanism and the potential of 4-FBS in diabetic neuropathic pain.

6-Methoxyflavanone abates cisplatin-induced neuropathic pain apropos anti-inflammatory mechanisms: A behavioral and molecular simulation study.

Cisplatin is used as a first line therapy in treating cancers. However, its use is often accompanied with the development of peripheral neuropathy. 6-Methoxyflavanone (6-MeOF) is a positive allosteric modulator at GABAA receptors and is known for attenuating diabetes-induced neuropathic pain. Neuropathy was induced in male Sprague-Dawley rats (150-250 g), via intraperitoneal injection of cisplatin (3 mg/kg) once a week for four consecutive weeks. 6-MeOF (25, 50 and 75 mg/kg, i.p) and gabapentin (75 mg/kg, i.p) were administered 30 min before each cisplatin injection. Static and dynamic allodynia were assessed using von Frey filaments and cotton buds. The anti-inflammatory activity was analyzed with plethysmometer. Body weights were also measured each week. The binding affinity of 6-MeOF with chloride channel, Cyclooxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2) was studied using docking approach. The in vitro COX-1 and COX-2 inhibitory effect of 6-MeOF was conducted with COX colorimetric assay. Administration of cisplatin for four consecutive weeks induced static (decreased paw withdrawal threshold; PWT) and dynamic allodynia (decreased paw withdrawal latency; PWL). Co-administration of 6-MeOF for four weeks significantly attenuated the cisplatin-induced expression of nocifensive behaviors observed as significant increase in PWT and PWL. Moreover, it also prevented the body weight loss induced by cisplatin administration. In silico studies depicted a good interaction of 6-MeOF with chloride ion channels and COX-1 and COX-2 enzymes. The in vitro study confirmed the inhibitory activity of 6-MeOF for COX-1 and COX-2. 6-MeOF may be effective in attenuating cisplatin-induced allodynia, probably through interaction with GABAergic receptors and reducing inflammation.

Efficient broadband light absorption in thin-film a-Si solar cell based on double sided hybrid bi-metallic nanogratings.

Thin film solar cells (TFSCs) suffer from poor light absorption due to their small thickness, which limits most of their practical applications. Surface plasmons generated by plasmonic nanoparticles offer an opportunity for a low-cost and scalable method to optically engineer TFSCs. Here, a systematic simulation study is conducted to improve the absorption efficiency of amorphous silicon (a-Si) by incorporating double sided plasmonic bi-metallic (Al-Cu) nanogratings. The upper pair of the gratings together with an antireflection coating are responsible for minimizing the reflection losses and enhancing the absorption of low wavelength visible light spectrum in the active layer. The bottom pairs are accountable for increasing the absorption of long wavelength photons in the active layer. In this way, a-Si, which is a poor absorber in the long wavelength region, is now able to absorb broadband light from 670-1060 nm with an average simulated absorption rate of more than 70%, and improved simulated photocurrent density of 22.30 mA cm-2, respectively. Moreover, simulation results show that the proposed structure reveals many other excellent properties such as small incident angle insensitivity, tunability, and remarkable structural parameters tolerance. Such a design concept is quite versatile and can be extended to other TFSCs.

Optical optimization of double-side-textured monolithic perovskite-silicon tandem solar cells for improved light management.

Tandem configuration-containing perovskite and silicon solar cells are promising candidates for realizing a high power conversion efficiency of 30% at reasonable costs. Silicon solar cells with planar front surfaces used in tandem devices cause high optical losses, which significantly affects their efficiency. Moreover, some studies have explored the fabrication of perovskites on textured silicon cells. However, due to improper texturing, light trapping is not ideal in these devices, which reduces the efficiency. In this work, we optimized the pyramid height of textured silicon cells and efficiently characterized them to achieve enhanced light trapping. Two different kinds of perovskites, namely, Cs0.17FA0.6Pb(Br0.17I0.7)3 and Cs0.25FA0.6Pb(Br0.20I0.7)3 with wide bandgaps were conformally deposited on textured silicon cells, and the performance of these flat and fully textured tandem devices was numerically analyzed. The thickness of each layer in the tandem cell was optimized in a way to ensure a perfect current match between the top perovskite and bottom silicon subcells. The results indicated that the textured tandem configuration enhances light absorption over a broad spectral range due to the optimized pyramid height compared to flat surfaces. Eventually, the photovoltaic parameters of the proposed tandem cell were compared with the already existing structures, and our design supports large values of open circuit voltage (V oc) = 1.78 V, short circuit current density (J sc) = 20.09 mA cm-2, fill factor (FF) = 79.01%, and efficiency (η) = 28.20% compared to other kinds of tandem solar cells.