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Poonam Ashish Gupte,1 Shital Ashok Giramkar,1 Shubhangi Mandar Harke,1 Sneha Keshav Kulkarni,1 Amol Panjabrao Deshmukh,2 Lal Lachhmandas Hingorani,2 Madhavi Prabhakar Mahajan,3 Supriya Sudhakar Bhalerao11Obesity Diabetes lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth Deemed University Campus, Pune, Maharashtra, India; 2Research and Development Department, Pharmanza Herbals Pvt. Ltd., Dharmaj, Gujrat, India; 3College of Ayurved, Bharati Vidyapeeth Deemed University Campus, Pune, Maharashtra, IndiaPurpose: Osteoarthritis is the single most common cause of disability in older adults with an estimated 10% to 15% prevalence in individuals above 60 years. The contemporary medications include nonsteroidal anti-inflammatory drugs acetaminophen, cyclooxygenase-2 inhibitors, and surgical interventions. In view of safety issues regarding their longterm use, necessitating search for effective and safe alternatives, we evaluated Capsule Longvida®, Optimized Curcumin prepared using solid lipid curcumin particles (SLCP) technology in patients with knee osteoarthritis.Patients and methods: Eligible patients fulfilling American College of Rheumatology Criteria were randomized to SLCP group (400 mg twice daily delivering 80 mg of curcumin per capsule) or Ibuprofen with placebo group (400 mg each once daily) for 90 days. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analog Scale (VAS) were used for clinical assessment of knee pain and function. Degree of knee flexion and swelling were also noted. Blood biochemistry included hemogram, blood urea, creatinine, Random blood sugar and inflammatory markers viz. PGE2, TNF α, IL6, IL1β and LTB4 while urine examination included degenerative marker CTX II. The parametric data was analyzed using unpaired t test while non-parametric data was analyzed using Friedman’s test or Mann Whitney t test as applicable. A level of p

Multi-drug resistance in bacteria is emerging as a major global health challenge, causing substantial harm in terms of mortality, morbidity, and financial strain on healthcare systems. These bacteria are constantly acquiring new virulence factors and drug-resistance mechanisms, which highlights the critical need for innovative antimicrobial medicines and identification of new therapeutic targets, such as Sortase A (EfSrtA ΔN59 ). EfSrtA ΔN59 , a transpeptidase significant for the adhesion and virulence of Enterococcus faecalis (E. faecalis), presents an attractive target for disrupting biofilm formation-a key factor in persistent infections. This study investigates the inhibitory effects of two natural flavonoids- Rutin Trihydrate and Quercetin, on EfSrtA ΔN59 and biofilm formation in E. faecalis. With in vitro enzymatic assays and biofilm quantification techniques, we demonstrate that both compounds significantly attenuate EfSrtA ΔN59 activity, thereby hindering bacterial biofilm formation. Rutin Trihydrate and Quercetin exhibited strong binding affinities to the EfSrtA ΔN59 enzyme, as confirmed by molecular docking and MD simulation studies. This was further substantiated by a notable reduction in biofilm biomass in bacterial cultures treated with these compounds. These findings highlight the potential of Rutin Trihydrate and Quercetin as promising candidates for the development of novel anti-virulence therapies aimed at mitigating E. faecalis infections, thereby offering a compelling alternative to traditional antibiotics., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baig, Karade, Ahmad, Khan, Haque, Webster, Faiyazuddin and Al-Qahtani.)

Herein, we demonstrated the in situ synthesis of g-C 3 N 4 /Ti 3 C 2 T x nano-heterostructures for hydrogen generation under UV visible light irradiation. The formation of the g-C 3 N 4 /Ti 3 C 2 T x nano-heterostructures was confirmed via powder X-ray diffraction and supported by XPS. The FE-SEM images indicated the formation of layered structures of MXene and g-C 3 N 4 . HR-TEM images and SAED patterns confirmed the presence of g-C 3 N 4 together with Ti 3 C 2 T x nanosheets, i.e. , the formation of nano-heterostructures of g-C 3 N 4 /Ti 3 C 2 T x . The absorption spectra clearly showed the distinct band gaps of g-C 3 N 4 and Ti 3 C 2 T x in the nano-heterostructure. The increase in PL intensity and broadening of the peak with an increase in g-C 3 N 4 indicated the suppression of electron-hole recombination. Furthermore, the nano-heterostructure was used as a photocatalyst for H 2 generation from water and methylene blue dye degradation. The highest H 2 evolution (1912.25 μmol/0.1 g) with good apparent quantum yield (3.1%) and an efficient degradation of MB were obtained for gCT-0.75, which was much higher compared to that of the pristine materials. The gCT-0.75 nano-heterostructure possessed a high surface area and abundant vacancy defects, facilitating the separation of charge carriers, which was ultimately responsible for this high photocatalytic activity. Additionally, TRPL clearly showed a higher decay time, which supports the enhancement in the photocatalytic activity of the gCT-0.75 nano-heterostructure. The nano-heterostructure with the optimum concentration of g-C 3 N 4 formed a hetero-junction with the linked catalytic system, which facilitated efficient charge carrier separation also responsible for the enhanced photocatalytic activity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: : To assess the impact of early intervention services provided to children with visual loss and to report how parents perceive them in terms of a child's development and the family dynamics., Methods: : A qualitative descriptive study was conducted on a purposively selected sample of 15 children with severe visual impairment, availing early intervention services at a tertiary care facility in Pune, Maharashtra. Data were collected by conducting in-depth interviews of the parents with the help of a semi-structured interview topic guide. Participants were asked in detail about how and whether various components of the early intervention program (EIP) had an impact on their child. The interviews were audio-recorded, transcribed, and translated into English, and the resultant textual data were analyzed using the qualitative research software NVIVO 12 to identify themes and sub-themes under each domain., Results: : A total of 15 children were included in the study, with ages ranging from 13 months to 5 years. All the children included in the study suffered from severe visual impairment in infancy (Vision 3/60 - PL). In the course of this EIP, the majority of the children showed consistent progress in various aspects of child development. According to the parents, the most beneficial components of EIP were visual stimulation exercises, an improvised teaching methodology, and counseling services., Conclusion: : Almost all the parents included in the study reported a positive change in the behavior and development of the child as well as improved family dynamics after implementation of EIP., Competing Interests: None

A novel, highly sensitive gold nanowire (AuNW) resistive sensor is reported here for humidity sensing in the relative humidity range of 11% to 92% RH as well as for breath sensing. Both humidity and breath sensors are widely needed. Despite a lot of research on humidity and breath sensors, there is a need for simple, inexpensive, reliable, sensitive and selective sensors, which will operate at room temperature. Here we have synthesized gold nanowires by a simple, wet chemical route. The nanowires synthesized by us are 4-7 nm in diameter and a few micrometers long. The nanowires are amine functionalized. The sensor was prepared by drop casting gold nanowires on an alumina substrate to form a AuNW layer with different thicknesses (10, 20, 30 μm). The AuNW sensor is highly selective towards humidity and shows minimum cross sensitivity towards other gases and organic vapors. At an optimum thickness of 20 μm, the humidity sensing performance of the AuNW sensor over 11% to 92% RH was found to be superior to that of 10 and 30 μm thick layers. The response time of the sensor is found to be 0.2 s and the recovery time is 0.3 s. The response of the AuNW sensor was 3.3 MΩ/% RH. Further, the AuNW sensor was tested for sensing human breathing patterns., Competing Interests: There is no conflict of interest to report., (This journal is © The Royal Society of Chemistry.)

Sigma-1 and sigma-2 receptors are emerging therapeutic targets. We have identified that simple ammonium salts bind to these receptors and are effective in vivo. Radioligand binding assays were used to obtain structure-activity relationships of these salts. MTS assays were performed to determine their effect on growth in MCF7 and MDA-MB-486 cells. Anticancer properties were tested in NMRI mice transplanted with a fragment of mouse adenocarcinoma (MAC13). Antidepressant activity was tested using the forced-swim test and tail suspension tests. Dipentylammonium (K i 43 nM), tripentylammonium (K i 15 nM) and trihexylammonium (K i 9 nM) showed high affinity for the sigma-1 receptor. Dioctanoylammonium had the highest affinity (K 50 0.05 nM); this also showed the highest affinity for sigma-2 receptors (K i 13 nM). Dipentylammonium was found to have antidepressant activity in vivo. Branched-chain ammonium salts showed lower affinity. Bis(2-ethylhexyl)ammonium (K 50 29 µM), triisopentylammonium (K 50 196 µM) and dioctanoylammonium showed a low Hill slope, and fitted a 2-site binding model for the sigma-1 receptor. We propose this two-site binding can be used to biochemically define a sigma-1 receptor antagonist. Bis(2-ethylhexyl)ammonium and triisopentylammonium were able to inhibit the growth of tumours in vivo. Cheap, simple ammonium salts act as sigma-1 receptor agonists and antagonists in vivo and require further investigation.

Layer structured vanadium pentoxide (V 2 O 5 ) microparticles were synthesized hydrothermally and successfully decorated by a facile wet chemical route, with ∼10-20 nm sized ruthenium nanoparticles. Both V 2 O 5 and ruthenium nanoparticle decorated V 2 O 5 (1%Ru@V 2 O 5 ) were investigated for their suitability as resistive gas sensors. It was found that the 1%Ru@V 2 O 5 sample showed very high selectivity and sensitivity towards ammonia vapors. The sensitivity measurements were carried out at 30 °C (room temperature), 50 °C and 100 °C. The best results were obtained at room temperature for 1%Ru@V 2 O 5 . Remarkably as short a response time as 0.52 s @ 130 ppm and as low as 9.39 s @ 10 ppm recovery time at room temperature along with high selectivity towards many gases and vapors have been noted in the 10 to 130 ppm ammonia concentration range. Short response and recovery time, high reproducibility, selectivity and room temperature operation are the main attributes of the 1%Ru@V 2 O 5 sensor. Higher sensitivity of 1%Ru@V 2 O 5 compared to V 2 O 5 has been explained and is due to dissociation of atmospheric water molecules on 1%Ru@V 2 O 5 as compared to bare V 2 O 5 which makes hydrogen atoms available on Brønsted sites for ammonia adsorption and sensing. The presence of ruthenium with a thin layer of oxide is clear from X-ray photoelectron spectroscopy and that of water molecules from Fourier transform infrared spectroscopy., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Purpose: Osteoarthritis is the single most common cause of disability in older adults with an estimated 10% to 15% prevalence in individuals above 60 years. The contemporary medications include nonsteroidal anti-inflammatory drugs acetaminophen, cyclooxygenase-2 inhibitors, and surgical interventions. In view of safety issues regarding their longterm use, necessitating search for effective and safe alternatives, we evaluated Capsule Longvida ® Optimized Curcumin prepared using solid lipid curcumin particles (SLCP) technology in patients with knee osteoarthritis. Patients and methods: Eligible patients fulfilling American College of Rheumatology Criteria were randomized to SLCP group (400 mg twice daily delivering 80 mg of curcumin per capsule) or Ibuprofen with placebo group (400 mg each once daily) for 90 days. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analog Scale (VAS) were used for clinical assessment of knee pain and function. Degree of knee flexion and swelling were also noted. Blood biochemistry included hemogram, blood urea, creatinine, Random blood sugar and inflammatory markers viz. PGE2, TNF α, IL6, IL1β and LTB4 while urine examination included degenerative marker CTX II. The parametric data was analyzed using unpaired t test while non-parametric data was analyzed using Friedman's test or Mann Whitney t test as applicable. A level of p <0.05 was considered as statistically significant. Results: Out of 50 recruitments, 25 from the Ibuprofen group and 17 from the SLCP group completed the study with significant improvements in VAS and WOMAC scores indicating comparable efficacy of SLCP in alleviating pain with Ibuprofen. None of the markers displayed significant changes. Except one withdrawal in the study group due to rash and itching, the study drug was found safe. Conclusions: SLCP in a dose of 160 mg daily was found to be effective and safe in alleviating symptoms in patients suffering from knee osteoarthritis when administered for 90 days., Competing Interests: The authors report no conflicts of interest in this work.

Background: Brucellosis is a zoonotic infection. Humans contract brucellosis through inhalation of aerosolized infected particles, or when they come in direct contact with infected animal parts, or on consuming unpasteurised dairy products. It can affect multiple organs and systems. Endocarditis is diagnosed late in the course of the disease with mostly aortic valve involvement with serious morbidity and mortality., Case Summary: We report a case series of four patients with Brucella endocarditis. The first patient presented with fever, malaise, and exertional breathlessness. He underwent aortic valve replacement for refractory heart failure and bulky vegetations after failed medical therapy. The second patient presented with fever, breathlessness New York Heart Association (NYHA) III, with arthralgia, myalgia, anorexia, and weight loss. In view of aortic abscess with impending rupture and compression of left main coronary artery, aortic valve replacement was performed on the 4th day of antibiotic treatment. The third patient presented with fever, fatigue, NYHA II, and developed peripheral embolization but responded to medical treatment alone. The fourth patient presented with intermittent fever for 7 months. During hospitalization, he suffered acute limb ischaemia and stroke with absence of left dorsalis pedis and posterior tibial pulsation. Brucella IgG ELISA was positive. Mitral valve replacement was done subsequently with unremarkable hospital course., Discussion: Brucellosis is a challenging diagnosis to make. The diagnosis and treatment is often delayed as it presents with non-specific symptoms and signs. Cardiac involvement occurs in only 2% of the cases, but accounts for 80% of the mortality due to brucellosis. Brucella endocarditis should be suspected in cases of endocarditis with negative blood cultures and a risk of exposure. The most accepted treatment for Brucella endocarditis is a combination of antimicrobial therapy with surgery., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Coronary artery ectasia (CAE) is defined as a localised or diffuse dilatation of coronary artery lumen more than 1.5 times that of an adjacent normal segment. CAE may present with or without functionally significant stenosis. Such patients may manifest with stable angina or with acute coronary syndrome. Ectasia may serve as a nidus for thrombus formation with likelihood of distal embolisation or it may lead to dissection or spasm. This condition presents a challenge for an interventionist. Should we intervene or manage it medically. We describe a case of CAE where all the vessels were diffusely ectatic with variable degree of stenosis. In brief we discuss the causes and management issues in ectasia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary arterial hypertension (PAH) in which the pulmonary thrombus fails to resolve, resulting in occlusion and remodelling of pulmonary arteries. 1 Timely diagnosis is critical since it is potentially curable by pulmonary thromboendarterectomy. Twenty five per cent of cases do not have a history of thromboembolic event. The diagnosis should be considered in the diagnostic work-up of PAH despite lack of history of episodes of thromboembolism. Here we are reporting a case of CTEPH with multiple systemic to pulmonary collaterals delineated by angiogram and CT., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Monodispersed and highly luminescence cadmium selenide (CdSe) quantum dots (QDs) have been prepared in a single pot by colloidal reaction method. The QDs were characterized using X-ray diffraction (XRD), Raman Spectroscopy, transmission electron microscope (TEM), energy dispersive spectroscopy (EDS), UV-visible absorption spectroscopy and photoluminescence (PL) spectroscopy to study the structural, morphological, compositional and optical properties. The growth temperature played an important role to control the particle size. The optical wavelength was found to be shifted systematically from 460 nm to 575 nm upon increasing the reaction temperature from 110 °C to 260 °C. The size of CdSe QDs, ~2-4 nm was estimated from absorption data. The emission tail exhibited at higher wavelength in PL measurement for the QDs synthesized for lower reaction temperature revealed the presence of surface trap-states. A cubic crystal structure of CdSe QDs was revealed by XRD analysis. The spherical QDs of size 2 to 4.5 nm were observed from TEM analysis for the samples prepared at 140 °C, 200 °C and 260 °C. The sizes of QDs obtained by TEM are in good agreement with the results obtained from optical and XRD data. High resolution transmission electron microscopy (HRTEM) confirmed the cubic crystal structure of CdSe QDs. The Selected area diffraction (SAD) pattern exhibited diffused ring corresponds to (111), (220) and (311) reflections of cubic structure of CdSe. The compositional analysis studied by EDS revealed the growth of nearly stoichiometric CdSe QDs. The LO1 vibrational mode observed about 202-205 cm-1 decreases the broadening systematically upon increasing the reaction temperature.

Background and Aims: Atherosclerosis, the root cause of cardiovascular disease (CVD), has a number of risk factors-some modifiable and some not. CVD increases in women particularly during the postmenopausal period. Small dense low-density lipoprotein (sdLDL), a subclass of LDL, is an important determinant of atherosclerosis in postmenopausal women. Paraoxonase1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that prevents oxidative modifications in LDL and HDL. With this background, we studied the sdLDL-C, PON1 and lipid profile in postmenopausal women to compare between quality and quantity of LDL., Methods: We studied 80 pre- and postmenopausal women (40/group). The following parameters were studied: lipid profile, sdLDL-C and PON1 levels. With proper statistical tools the correlation between these parameters was studied., Results: Postmenopausal women, in comparison with premenopausal women, have significantly increased levels of serum triglycerides and sdLDL-C and very-low-density lipoprotein cholesterol (VLDL-C) and significantly decreased levels of HDL-C and PON1. PON1 activity was negatively correlated with age, TC, TG, LDL-C and sdLDL-C (r = -0.574, -0.119, -0.226, -0.473 and -0.455, respectively) and positively correlated with HDL-C (r = 0.368), whereas sdLDL-C was positively correlated with age, TC, TG, LDL-C (r = 0.633, 0.485, 0.561 and 0.705, respectively) and negatively with HDL-C (r = -0.235). Stepwise multiple regression analysis demonstrated HDL-C and menopausal status as the best determinant for PON1 (R(2) = 0.320, p < 0.05) and menopausal status, LDL-C, TG, and TC were the best determinants for sdLDL-C (R(2) = 0.606, p < 0.05)., Conclusion: The results of the present study suggest quality, i.e., sdLDL-C, is more important than only LDL-C levels. Similarly, decrease in PON1 and increase in sdLDL-C go hand in hand. This shows that antioxidant capacity is compromised with a qualitative downfall in lipoproteins in postmenopausal women., (Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.)

Curcumin, obtained from Curcuma longa, has been in use for manifold human disorders. The present study explores the effect of curcumin against pentylenetetrazol (PTZ) seizure threshold in mice. The possible involvement of adenosine receptor(s) mechanism was also investigated. Minimal dose of PTZ (i.v., mg/kg) needed to induce different phases of convulsions were recorded as an index of seizure threshold. Curcumin (20-120 mg/kg, p.o.) produced an increase in seizure threshold for convulsions induced by PTZ i.v. infusion. The anticonvulsant effect of curcumin (80 mg/kg) was prevented by 8-phenyltheophylline (0.5 mg/kg, i.p., non-selective adenosine receptor antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (5 mg/kg, i.p., adenosine A1 receptor antagonist) but not by 8-(3-cholorostryl)caffeine (4 mg/kg, i.p., adenosine A2A receptor antagonist). Further, 5'-N-ethylcarboxamidoadenosine (0.005 mg/kg, i.p., non-selective A1 /A2 receptor agonist), or N(6) -cyclohexyladenosine (0.2 mg/kg, i.p., adenosine A1 receptor agonist), was able to potentiate the anticonvulsant action of curcumin. In contrast, 5'-(N-cyclopropyl) carboxamidoadenosine (0.1 mg/kg, i.p., adenosine A2A receptor agonist) failed to potentiate the effect of curcumin. This study demonstrated the anticonvulsant effect of curcumin against PTZ i.v. seizure threshold via a direct or indirect activation of adenosine A1 but not A2A receptors in mice. Thus, curcumin may prove to be an effective adjunct in treatment of convulsions., (Copyright © 2013 John Wiley & Sons, Ltd.)

Umbilical venous pH is claimed to mirror fetal acid-base status. Importantly, it is easier to perform. The aim of this study is to : 1. Evaluate the umbilical venous blood gas (UVBG) profile of normal newborns and to compare UVBG in the following situations: presence or absence of asphyxia presence or absence of meconium-stained amniotic fluid presence or absence of respiratory distress: and in newborns that did and did not survive and 2. To study the peripheral venous blood gas (PVBG) profile of newborns that develop cardio-respiratory insufficiency (CRI). Venous blood gas (VBG) was performed in 961 newborns consecutively admitted to the neonatal nursery over one year and in 100 controls. PVBG was also performed in 370 admissions to the nursery that developed signs of CRI. Demographic, clinical and outcome data were collected. Mean UVBG parameters (pH, pCO 2 , HCO 3 , base deficit, pO 2 and SO 2 %) were compared between different groups of newborns using t test. This study had ethical approval. Of the 3349 live births over one year, 961 (28.7%) needed intensive care. Of these, 123 (12.8%) died. All the mean cord gas parameters differed significantly between who died and who survived. Metabolic acidosis and hypoxemia were conspicuous on PVBG among babies with CRI. Except for PO 2 all the mean parameters of UVBG differed significantly with asphyxia and meconium-stained amniotic fluid. When similar comparison was made among newborns that did or that did not develop respiratory distress, the difference was significant for all the parameters except SO 2 %. UVBG gives useful information about common neonatal morbidities and appears to be a useful tool for neonatal assessment. PVBG gives objective information about babies with CRI that may need special interventions.

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and validated for the estimation of tenoxicam in the microemulsion gels. Tenoxicam was chromatographed on silica gel 60 F(254) TLC plate, as a stationary phase. The mobile phase was toluene: ethyl acetate: formic acid (6:4:0.3 v/v/v), which gave a dense and compact spot of tenoxicam with a R(f) value of 0.38±0.03. The quantification was carried out at 379 nm. The method was validated in terms of linearity, accuracy, precision and specificity. To justify the suitability, accuracy and precision of the proposed method, recovery studies were performed at three concentration levels. Statistical analysis proved that the proposed method is accurate and reproducible with linearity in the range of 100 to 400 ng. The limit of detection and limit of quantification for tenoxicam were 25 and 50 μg/spot, respectively. The proposed method can be employed for the routine analysis of tenoxicam as well as in pharmaceutical formulations.

Background: Curcumin is the active principle of Curcuma longa, one of the widely used components in the traditional system of medicine in India. Despite its efficacy in experimental studies aiming at neuronal disorders like depression, curcu-min's poor water solubility challenges the production of therapeutic formulations. This study investigates the antidepressant-like activity of novel water-soluble curcumin formulations, dispensed in three different concentrations. Further, the study comparatively evaluates St. John's wort (SJW), another herbal preparation., Methods: These compounds were evaluated in the forced swimming test in mice, and the corresponding changes in the neurotransmitter levels were measured., Results: Three water-soluble curcumin formulations, C-5, C-20 and C-50 (50-200 mg/kg p.o.) decreased the immobility period, and increased serotonin and dopamine levels in the brain tissues. A subeffective dose (50 mg/kg) of these formulations enhanced the antidepressant-like effect of classical antidepressants with varied mechanisms of action. In addition, an SJW dose of 25 mg/kg showed a significant antidepressant-like effect in all the behavioral studies and also significantly increased brain neurotransmitter levels, especially that of serotonin. The effects produced by C-5 were comparable with those of SJW and fluoxetine, respectively., Conclusion: In all these observations, the water-soluble formulations showed a significant antidepressant-like effect, including enhancement of neurotransmitter levels as compared to the similar dose of a conventional curcumin preparation. Thus, these formulations may be used as a novel treatment option in the management of mental depression., (Copyright © 2012 S. Karger AG, Basel.)

1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol is a novel putative trace amine receptor modulator hypothesized to be useful for treatment-resistant depression. In our previous study, we have demonstrated the antidepressant-like effect of this molecule in mouse forced swim and tail suspension tests and shown to act via modulating the levels of norepinephrine, serotonin and dopamine. The present study attempts to explore the involvement of l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol in the mouse forced swim test. The antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (8 mg/kg, i.p) was reversed by pretreatment with L-arginine (750 mg/kg, i.p.), a nitric oxide precursor. In contrast, pretreatment with methylene blue (a soluble guanlyate cyclase inhibitor and nitric oxide synthase (NOS) inhibitor) or 7-nitroindazole (a specific neuronal NOS inhibitor) potentiated the antidepressant-like effect of sub-effective dose of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (2mg/kg, i.p.) in this test model. Furthermore, the antidepressant-like effect of this molecule (8 mg/kg, i.p.) was reversed by sildenafil (5mg/kg, i.p.), a phosphodiesterase inhibitor. In conclusion, the antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol involved L-arginine-nitric oxide-cyclic guanosine monophospate signaling pathway., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects, particularly the irregular movements of chorionic type. This limitation presents a marked therapeutic challenge. The present study investigates the molecular etiology of haloperidol neurotoxicity and the role of curcumin, a well-known anti-oxidant, in ameliorating these adverse effects. The redox status of haloperidol-treated brains along with NO, TNF-α, NF-kappaB p65 subunit, caspase-3, and monoamine neurotransmitters were measured in the striatum of rat brain. Chronic treatment with haloperidol (5 mg/kg, i.p., 21 days) produced orofacial dyskinetic movements which were coupled with marked increase in oxidative stress parameters, TNF-α, caspase-3 activity in cytoplasmic lysate and active p65 sub unit of NF-kappaB in nuclear lysates of the striatum. Neurochemically, chronic administration of haloperidol resulted in a significant decrease in the levels of norepinephrine, dopamine, and serotonin. The prototype atypical anti-psychotic, clozapine (10 mg/kg, i.p., 21 days) produced mild oxidative stress but did not alter any other parameters. Interestingly, co-administration of curcumin (25 and 50 mg/kg, i.p., 21 days) dose-dependently prevented all the behavioral, cellular, and neurochemical changes associated with the chronic administration of haloperidol. Curcumin per se (50 mg/kg) did not show any side effects. Co-administration of piperine significantly enhanced the effect of curcumin (25 mg/kg) but not of curcumin (50 mg/kg). Collectively, the data indicated the potential of curcumin as an adjunct to haloperidol treatment and provided initial clues to the underlying molecular mechanisms in haloperidol neurotoxicity. This study also provides a rationale for the combination of piperine and curcumin.