Nanonization of Magnoflorine-Encapsulated Novel Chitosan-Collagen Nanocapsules for Neurodegenerative Diseases: In Vitro Evaluation.

Neurodegeneration is one of the most common diseases in the aged population, characterized by the loss in the function of neuronal cells and their ultimate death. One of the common features in the progression of this type of diseases is the oxidative stress. Drugs which are currently being used have been found to show lateral side effects, which is partly due to their inefficiency to cross blood-brain barrier. Nanoencapsulation of bioactive compounds is a profound approach in this direction and has become a method of choice nowadays. This study involved the evaluation of the anti-oxidative properties of magnoflorine (MF), which is an aporphine quaternary alkaloid, and synthesis of MF-loaded chitosan-collagen nanocapsules (MF-CCNc) for its better efficacy as a potent anti-oxidant. Physiochemical characterization of the synthesized nanocapsules was done by using dynamic light scattering and transmission electron microscopy. It revealed that the synthesized nanocapsules are of small size range, as small as 12 ± 2 nm, and are more or less of spherical shape. Sustained release was shown by MF in the in vitro drug release studies. Both MF and MF-CCNc were found to have good anti-oxidant potential with IC50 < 25 µg/mL. No major cytotoxicity was shown by the synthesized nanocapsules on SH-SY5Y cells. In silico anti-acetylcholinesterase (AChE) studies were also done, and they revealed that MF can be a potent inhibitor of AChE.

Venous thromboembolism is linked to severity of disease in COVID-19 patients: A systematic literature review and exploratory meta-analysis.

PURPOSE: Coronavirus disease-2019 (COVID-19) may predispose to venous thromboembolism (VTE) and arterial thromboembolism because of excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. Thus, in this meta-analysis, we aim to assess the association of VTE with the severity of COVID-19 disease. METHODS: A literature search was conducted on PubMed and Cochrane Central Register of Controlled Trials using the keywords "COVID-19 and thromboembolism" and "COVID-19 and embolism," till 20 February 2021. Thirteen studies including 6648 COVID-19 patients were incorporated in this systematic review and exploratory meta-analysis. RESULTS: The analysis revealed nearly three times more risk than intensive care unit (ICU) care in patients with VTE compared to non-VTE patients (RR: 2.78; 95% CI: 1.75-4.39; P < .001; I2 : 65.1%). Patients with pulmonary embolism and deep vein thrombosis are at increased risk of being admitted to ICU (RR: 2.21; 95% CI: 1.86-2.61; P < .001; I2 : 41.2%) and (RR: 2.69; 95% CI: 2.37-3.06; P < .001; I2 : 0.0%), respectively. The quality assessment indicated that the included studies were of fair quality. CONCLUSIONS: Our findings suggest that VTE either deep vein thrombosis or pulmonary embolism may have a negative effect on the health status of COVID-19 patients. This study highlights the need to consider measures for reducing thromboembolism risk amongst COVID-19 patients.

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice.

Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3',4',7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties. This study investigated the neuroprotective effect of fisetin on experimental epilepsy. For acute studies, increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizure tests were performed to evaluate the antiseizure activity of fisetin. For the chronic study, the kindling model was established by the administration of PTZ in subconvulsive dose (25 mg/kg, i.p.). Mice were treated with fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable antiseizure mechanism. The kindled mice were evaluated for seizure scores. Their hippocampus and cortex were assessed for neuronal damage, inflammation, and apoptosis. Histological alterations were observed in the hippocampus of the experimental mice. Levels of high mobility group box 1 (HMGB1), Toll-like receptor-4 (TLR-4), interleukin-1 receptor 1 (IL-1R1), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed in the hippocampus and cortex by ELISA. The immunoreactivity and mRNA expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), cytochrome C, and caspase-3 were quantified by immunohistochemical analysis and real-time PCR. Phosphorylation ELISA was performed to evaluate AkT/mTOR (mammalian target of rapamycin) activation in the hippocampus and cortex of the kindled mice. The results showed that fisetin administration increased the seizure threshold current (STC) in the ICES test. In PTZ-induced seizures, fisetin administration increased the latency for myoclonic jerks (MJs) and generalized seizures (GSs). In the PTZ-induced kindling model, fisetin administration dose-dependently suppressed the development of kindling and the associated neuronal damage in the experimental mice. Further, fisetin administration ameliorated kindling-induced neuroinflammation as evident from decreased levels of HMGB1, TLR-4, IL-1R1, IL-1ß, IL-6, and TNF-α in the hippocampus and cortex of the kindled mice. Also, the immunoreactivity and mRNA expressions of inflammatory molecules, NF-κB, and COX-2 were decreased with fisetin administration in the kindled animals. Decreased phosphorylation of the AkT/mTOR pathway was reported with fisetin administration in the hippocampus and cortex of the kindled mice. The immunoreactivity and mRNA expressions of apoptotic molecules, cytochrome C, and caspase-3 were attenuated upon fisetin administration. The findings suggest that fisetin shows a neuroprotective effect by suppressing the release of inflammatory and apoptosis molecules and attenuating histological alterations during experimental epilepsy.

Evaluation of Stress and Associated Biochemical Changes in Patients with Type 2 Diabetes Mellitus and Obesity.

PURPOSE: Type 2 diabetes mellitus (T2DM), a metabolic disorder, remains associated with a physiological impairment affecting large populations worldwide. Onset of T2DM is multifactorial where obesity and abnormal basal metabolic rate are considered most critical. Of people diagnosed with T2DM, about 80% are also obese. It is also reported that obese individuals have an increased odds of developing depression, whereas T2DM is estimated to increase the incidence by two-fold. The preponderance of research data demonstrates that T2DM alters the serum level of cortisol and adiponectin which are known to be associated with neuronal physiology. The study explored, how a metabolic disorder like T2DM is linked with the altered plasma level of cortisol and adiponectin, the risk factors for stress and depression. PATIENTS AND METHODS: A cross-sectional population study was conducted in T2DM patients using a bimodal approach. First approach used questionnaires, (1) Patient Health Questionnaire (PHQ-9) and (2) Stress Coping Inventory Questionnaire (SCQ) to assess signs and symptoms of depression and stress, respectively, in T2DM patients. In the second approach, robust biochemical analysis was conducted for serum adiponectin and cortisol levels. RESULTS: An association of T2DM in stress and depression was evaluated in 158 subjects (105 T2DM obese patients and 53 healthy controls). A lower PHQ-9 score and adiponectin levels were seen in T2DM obese patients compared to healthy controls (p<0.05). Further, results also depicted a lower adiponectin levels in T2DM obese patients with depression compared to T2DM obese patients without depression (p<0.05). The study did not find a significant difference in cortisol serum levels among the T2DM and control groups. However, a higher level of serum cortisol was reported in T2DM obese patients with depression over those T2DM obese patients who lacked depression (p<0.05). CONCLUSION: The findings suggest that T2DM obese patients might have a higher risk of developing stress and depression. Further, biochemical parameters, adiponectin and cortisol, might be the potential biomarkers for T2DM and may help in early diagnosis of these comorbid conditions.

Impact of cardiovascular diseases on severity of COVID-19 patients: A systematic review.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) cases are increasing rapidly worldwide. Similar to Middle East respiratory syndrome where cardiovascular diseases were present in nearly 30% of cases, the increased presence of cardiovascular comorbidities remains true for COVID-19 as well. The mechanism of this association remains unclear at this time. Therefore, we reviewed the available literature and tried to find the probable association between cardiovascular disease with disease severity and mortality in COVID-19 patients. METHODS: We searched Medline (via PubMed) and Cochrane Central Register of Controlled Trials for articles published until Sept 5, 2020. Nineteen articles were included involving 6,872 COVID-19 patients. RESULTS: The random-effect meta-analysis showed that cardiovascular disease was significantly associated with severity and mortality for COVID-19: odds ratio (OR) 2.89, 95% confidence interval (CI) 1.98-4.21 for severity and OR 3.00, 95% CI 1.67-5.39 for mortality, respectively. Risk of COVID-19 severity was higher in patients having diabetes, hypertension, chronic obstructive pulmonary disease, malignancy, cerebrovascular disease and chronic kidney disease. Similarly, patients with diabetes, hypertension, chronic liver disease, cerebrovascular disease and chronic kidney disease were at higher risk of mortality. CONCLUSION: Our findings showed that cardiovascular disease has a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid cardiovascular disease are urgently needed to understand the extent of these concerning comorbidities.

Embelin ameliorates cognitive dysfunction and progression of kindling in pentylenetetrazol-induced kindling in mice by attenuating brain inflammation.

OBJECTIVE: This study was conducted to evaluate the effect of embelin (EMB) on various epileptic models and related brain inflammation. METHODS: Male Swiss albino mice were administered EMB (5, 10, and 20 mg/kg/p.o.) in acute and chronic study for 7 days and 35 days, respectively. Acute study included increasing current electroshock (ICES) and pentylenetetrazol (PTZ)-induced seizure test. Step-down latency (SDL) and forced swim test (FST) were performed to evaluate cognitive functions and depression-like behavior, respectively. Chronic study included PTZ-induced kindling. Levels of inflammatory biomarkers, namely interleukin-1 beta (IL-1ß), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were estimated in the hippocampus and cortex of the kindled brains by ELISA technique. Further, neurotransmitters (NTs), namely gamma aminobutyric acid (GABA), glutamate, and dopamine, were estimated by using validated liquid chromatography-mass spectrometry (LC-MS) method followed by ultra-high-performance liquid chromatography (UHPLC). RESULTS: Embelin (EMB) treatment increased the seizure threshold to hind limb extension (HLE) in the ICES test and decreased the seizure scores in the kindling experiment. Significantly low levels of IL-1ß, IL-1Ra, IL-6, and TNF-α were observed in the hippocampus of PTZ + EMB (10 and 20 mg/kg)-treated groups compared with PTZ+ vehicle-treated group. Significantly lower levels of IL-1Ra, IL-6, and TNF-α compared with PTZ+ vehicle-treated group were observed in the cortex of PTZ + EMB (10 and 20 mg/kg)-treated groups, while IL-1ß levels were found to be significantly lower only in the cortex of PTZ + EMB (20 mg/kg)-treated group. Increased levels of dopamine and GABA and decreased levels of glutamate in both hippocampus and cortex were observed in EMB + PTZ-treated groups compared with vehicle + PTZ-treated group. Latency of step down was found to be increased and immobility time in FST was decreased in EMB + PTZ groups compared with vehicle + PTZ group. CONCLUSION: Embelin suppressed epileptogenesis in the kindled mice via neurochemical modulation of neurotransmitters and inhibiting the inflammatory pathway. Further, EMB was also observed to be protecting the kindled animals from cognition and depression-like behavior.

Biofabricated platinum nanoparticles: therapeutic evaluation as a potential nanodrug against breast cancer cells and drug-resistant bacteria.

Use of plant extracts for the synthesis of various metal nanoparticles has gained much importance recently because it is a simple, less hazardous, conservative and cost-effective method. In this research work, platinum nanoparticles were synthesized by treating platinum ions with the leaf extract of Psidium guajava and their structural properties were studied using various characterization techniques. The formation of platinum nanoparticles was confirmed by the disappearance of the absorbance peak at 261 nm in UV-visible spectra. The results of gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy (FT-IR) analysis showed functional moieties responsible for bio-reduction of metal ions and stabilization of platinum nanoparticles. The use of dynamic light scattering (DLS) imaging techniques confirmed the formation of stable monodispersed platinum nanoparticles showing a zeta potential of -23.4 mV. The morphological examination using high resolution transmission electron microscopy (HR-TEM) and Scanning electron microscopy (SEM) confirmed the formation of spherical platinum nanoparticles with an average diameter of 113.2 nm. X-ray powder diffraction (XRD) techniques showed the crystalline nature of biosynthesized platinum nanoparticles with a face-centered cubic structure. The results of energy-dispersive X-ray spectroscopy (EDAX) showed 100% platinum content by weight confirming the purity of the sample. The cytotoxic effect of biosynthesized platinum nanoparticles assessed in a breast cancer (MCF-7) cell-line by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, revealed an IC50 of 167.2 µg ml-1. The results of a wound healing assay showed that treatment with platinum nanoparticles induced an anti-migratory effect on MCF-7 cells. In the cell cycle phase distribution, treatment with platinum nanoparticles inhibited cell proliferation as determined by flow cytometry with PI staining. Significant cell cycle arrest was detected at the G0/G1 phase with a notable decrease in the distribution of cells in the S and G2/M phases. The anti-bacterial activity of bio-synthesized platinum nanoparticles was evaluated against four pathogenic bacteria i.e. B. cereus (Gram positive), P. aeruginosa (Gram negative), K. pneumonia (Gram negative) and E. coli (Gram negative). The biosynthesized platinum nanoparticles were found to show dose-dependent inhibition against pathogenic bacteria with a significant effect on Gram-negative bacteria compared to Gram-positive bacteria. This synergistic blend of green and simplistic synthesis coupled with anti-proliferative and anti-bacterial properties makes these biogenic nanoparticles suitable in nanomedicine.

Bio-engineered palladium nanoparticles: model for risk assessment study of automotive particulate pollution on macrophage cell lines.

The surge in vehicular activity in densely populated areas has led to an increased concentration of airborne palladium nanoparticles (PdNPs) in the environment. Recent toxicity data have indicated that PdNPs exhibit adverse effects in in vitro and in vivo models, however, their effect on the immune system is not fully understood. Therefore, in the present study, we aimed to evaluate possible toxic effects of bio-engineered palladium nanoparticles on the murine macrophage cell line (J774). Here we prepared palladium nanoparticles using aqueous leaf extract of Parthenium hysterophorus and characterized them by UV-Vis spectroscopy, XRD, FT-IR spectroscopy, HR-TEM, EDX, SEM and zeta potential. Toxicity parameters such as cell viability, cell membrane integrity, induction of apoptosis and ROS production were assessed on J774 cell lines. Spherical palladium nanoparticles of mean size ∼4 nm, when subjected to time and dose-dependent cytotoxicity assay, showed cell viability was >95% at lower doses (25, 200 µg mL-1) and <50% at higher doses of palladium nanoparticles (400, 500 µg mL-1) after 24 hours of incubation. We also observed cell membrane injury at higher doses by lactate dehydrogenase assay. The induction of apoptosis observed was moderate. H2DCFDA assay revealed visible cell damage which could be due to modest levels of ROS generation. The detection of Pd in the road-dust samples of New Delhi using inductively coupled plasma-mass spectroscopy (ICP-MS) technique was also investigated.

Association of diabetes and hypertension with disease severity in covid-19 patients: A systematic literature review and exploratory meta-analysis.

AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 COVID-19 patients. RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p = 0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p = 0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p<0.001; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p = 0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p = 0.01; I2: 52.4%). CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.

Invasive Fungal Infections in Patients with Acute Myeloid Leukemia Undergoing Intensive Chemotherapy.

Patients with hematological malignancies are severely immunocompromised and are at high risk of invasive fungal infection (IFI), particularly those undergoing remission-induction chemotherapy for acute myeloid leukemia (AML). IFIs are a major cause of morbidity and mortality in such patients. We planned to study the incidence of IFI in patients with AML undergoing intensive chemotherapy and receiving antifungal prophylaxis. We retrospectively reviewed consecutive 46 patients with non-M3 AML, who received induction chemotherapy and systemic antifungal prophylaxis. None of the patients had IFI at the time of initiation of the chemotherapy. Patients were monitored for the occurrence of IFI using high-resolution computerized tomography of the chest or para-nasal sinus and test for galactomannan antigen on serum or broncho-alveolar lavage and were followed up for 90 days. Of the 46 patients on intensive chemotherapies, 41, 4 and 1 patients were started on posaconazole, amphotericin B and voriconazole prophylaxis, respectively. The occurrence of possible and probable IFI was observed in 16 and 4 patients respectively, in which 19 patients were on posaconazole and 1 patient was on amphotericin-B prophylaxis. Overall mortality in the study population was 11 (23.9%). Four out of 20 patients died with IFI but none of the death was attributable to IFI. IFI still remains a significant cause of morbidity and mortality in patients with AML despite universal use of antifungal prophylaxis. With effective pharmacotherapy, the mortality due to IFI is preventable. Appropriate antifungal prophylaxis strategy still needs to be developed through larger and prospective studies.

Factors Influencing Participation Of Healthy Volunteers In Clinical Trials: Findings From A Cross-Sectional Study In Delhi, North India.

PURPOSE: To identify the specific motivations that drive healthy volunteers to consent for their participation in clinical studies. Additionally, the study aimed to document the socio-demographic determinants of participation in the trial related solely to the intention of securing financial gains. PATIENTS AND METHODS: This cross-sectional study was conducted among subjects who participated as healthy volunteers in clinical trials conducted by Contract Research Organizations (CROs) of Delhi. Pre-tested, validated semi-structured questionnaires were used to collect baseline socio-demographic data, information about factors motivating participation in clinical trials, and pattern of utilisation of money received against participation in the trial. Logistic regression analysis was done to determine the factors that influenced participation in the trial related purely to the motive of securing financial gains. RESULTS: A total of 400 participants were selected. The majority of the volunteers (77.5%) reported that their sole reason for participating in clinical trials was for monetary gain. Around a tenth of the volunteers participated with the intent to advance scientific knowledge and another 4.5% participated due to benefits of free medical check-ups. Participants in the age group of 29-38 years, those that were married, those residing in an urban slum, male participants, those with a high number of dependent family members (ie, 5 to 8), and those earning less than 5000 INR (71 USD) a month had higher odds of participating in a clinical trial purely for the financial benefits. Those educated till intermediate and above had lower odds of participation in the trial due to monetary benefits. CONCLUSION: Our study shows that healthy volunteers in Delhi consider participation in clinical trials mainly because of the prospect of financial reward. More research is needed to inform judgments around the ethics of providing financial rewards and enrollment of healthy research volunteers.

Attenuated serum 25-hydroxyvitamin D and vitamin D binding protein associated with cognitive impairment in patients with type 2 diabetes.

PURPOSE: Clinical studies suggest that 25-hydroxyvitamin D (25[OH]D) deficiency plays a pivotal role in both type 2 diabetes mellitus (T2DM) and cognitive impairment. However, it is unclear if 25(OH)D deficiency could be a possible cause of cognitive impairment in T2DM. Vitamin-D binding protein (VDBP) acts as a major 25(OH)D transporter. Preclinical study has demonstrated improvement in cognitive function by VDBP via inhibiting synaptic degeneration. The aim of the study was to assess the association between serum 25(OH)D, VDBP and cognitive impairment in T2DM patients. PATIENTS AND METHODS: In this case-control study, cognitive function was assessed using the Mini-Mental State Examination (MMSE) and serum 25(OH)D and VDBP levels were estimated using ELISA kits. RESULTS: A total of 88 subjects were included in the study. T2DM patients had lower serum 25(OH)D (p=0.02), VDBP levels (p=0.04) and MMSE scores (p<0.0001) than controls. T2DM patients had higher prevalence of 25(OH)D deficiency and insufficiency, aOR 0.322 (0.128-0.809), p=0.016 and cognitive impairment, aOR 4.405 (1.617-12.002); p=0.004. Cognitive impairment was associated with serum 25(OH)D, aOR 0.131 (0.027-0.638); p=0.014 and VDBP, aOR 1.008 (1.001-1.015), p=0.029. A general linear model showed a significant association of MMSE with serum 25(OH)D (p=0.022). CONCLUSION: Serum 25(OH)D deficiency and cognitive impairment was higher in T2DM patients. Routine assessment of cognitive function is suggested to prevent further behavioral complications. The association of VDBP and cognitive impairment in T2DM needs further exploration.

Resveratrol suppressed seizures by attenuating IL-1ß, IL1-Ra, IL-6, and TNF-α in the hippocampus and cortex of kindled mice.

OBJECTIVE: There is an urge to identify new molecules which can modulate process of epileptogenesis, since currently available drugs act symptomatically and one-third of the patients remain refractory to the disease. Hence, the present study was conducted to evaluate the effects of Resveratrol (RESV) on epileptogenesis in pentylenetetrazole (PTZ)-induced kindling in mice. METHOD: Swiss albino mice were administered RESV (10, 20 and 40 mg/kg,p.o) in acute study. On the seventh day animals were subjected to various neurological and neurobehavioral tests viz, Increasing Current Electroshock Test (ICES), PTZ-induced seizures, passive avoidance response, and elevated plus maze test. For the development of kindling PTZ was administered in a dose of 25 mg/kg, i.p. on every alternate day and RESV in all the three doses was administered daily. Seizure score was continuously monitored till the development of kindling and cognition tests were performed in the end of the study. The animals were sacrificed and levels of inflammatory biomarkers viz., IL-1ß, interleukin-1 receptor antagonist (IL1-Ra), IL-6, and TNF-α were assessed in the hippocampus and cortex of the kindled animals. RESULTS: RESV in all three doses increased the seizure threshold to hind limb extension in the ICES test. RESV in all the tested doses suppressed the development of kindling and reduced the levels of IL-1ß, IL1-Ra, IL-6, and TNF-α in kindled mice. CONCLUSION: RESV suppressed the development of kindling in mice and decreased the levels of inflammatory biomarkers in their hippocampus. RESV modified brain inflammation during epileptogenesis and found to possess nootropic activity in the kindled mice.

Early manifestation of mild cognitive impairment in B-cell non-Hodgkin's lymphoma patients receiving CHOP and rituximab-CHOP chemotherapy.

Existing evidence suggests that pro-inflammatory cytokines increases during chemotherapy which plays an intermediary role in Chemotherapy related cognitive impairment (CRCI) and thyroid dysregulation. Previous studies suggest that thyroid hormones are essential for neuronal development and neurotransmitter release. CHOP regimen has been the backbone of Non-Hodgkin's lymphoma (NHL) treatment from a decade but rituximab addition to CHOP (R-CHOP) has improved cure rates. However, their adverse event profile on behavior is not well studied on patients. In this study total 68 NHL patients were enrolled and divided equally in 2 groups as CHOP receiving (n = 34) and R-CHOP receiving (n = 34). Effects of R-CHOP and CHOP regimen on thyroid function, pro-inflammatory cytokines and cognitive function were determined at four time points that was from one day before 1st (TP0), 2nd (TP1), 3rd (TP2) and 4th (TP3) cycle of chemotherapy. Results indicated significant increase in levels of pro-inflammatory cytokines after each time point from TP0 to TP3of chemotherapy. Thyroid hormone levels i.e. T3, T4 were found significantly decreased and TSH was increased after each time point of both groups. MMSE score was found significantly decreased after each cycle of both groups. However, an inverse association was found between IL-1ß levels with TSH by applying correlation coefficient. Cognitive function was decreased in patients with decreased T3 and T4 levels and increased TSH. To conclude, patients receiving R-CHOP regimen were found to have more increased IL-6 and IL-1ß with more cognitive decline and thyroid abnormality as comparison to CHOP receiving patients.

Efficacy and safety of canagliflozin in type 2 diabetes mellitus: systematic review of randomized controlled trials.

BACKGROUND: Currently available antihyperglycemic agents (AHAs), despite being effective, do not provide adequate glycemic control in some cases and are associated with side effects. A sodium glucose co-transporter 2 inhibitor, canagliflozin, is a newer AHA, which acts by decreasing the reabsorption of filtered glucose thereby elevating the urinary glucose excretion in diabetics. AREAS COVERED: This systematic review was completed to assess the clinical effectiveness and safety of canagliflozin in T2DM. A literature search in PubMed, MEDLINE, Cochrane and ClinicalTrials.gov was conducted for randomized clinical trials of canagliflozin as an AHA by applying predetermined inclusion and exclusion criteria. Total 13 studies were included in the systematic review. The main outcomes assessed were change in HbA1c and fasting plasma glucose. EXPERT OPINION: Canagliflozin monotherapy or combination therapy has the potential to decrease inadequately controlled hyperglycemia in T2DM. It acts by a novel insulin independent mechanism which complements the action of the existing AHA and improves glycemic control and decreases the body weight. Safety profile of canagliflozin indicates lower number of hypoglycemic episodes. Some manageable adverse events include genital mycotic infections, urinary tract infections, osmotic diuresis-related events etc. These findings affirm the utility of canagliflozin in T2DM; however, data on long-term safety and efficacy are needed.

Atorvastatin prevents development of kindling by modulating hippocampal levels of dopamine, glutamate, and GABA in mice.

PURPOSE: Atorvastatin (ATV) is widely used for the treatment of dyslipidemias. Recent evidence has shown that ATV has protection effects against seizures. However, the effect of ATV on certain neurotransmitter and oxidative stress markers associated with seizures had not been reported. Therefore, the present study aimed to evaluate the effects of ATV on oxidative stress markers on whole brain and GABA, glutamate, and dopamine levels in the hippocampus of PTZ-kindled mice. Additionally, effects of ATV on animal models of seizures, anxiety, and depression were also assessed. MATERIALS AND METHODS: Swiss albino mice were given ATV (20, 40, and 80mg/kg/p.o.) in an acute study. On the seventh day, animals were subjected to various neurological and neurobehavioral tests, viz, increasing current electroshock (ICES) test, pentylenetetrazole (PTZ)-induced seizures, Elevated Plus Maze (EPM), and Forced Swim Test (FST). For the development of kindling, a subconvulsant dose of PTZ, i.e., 25mg/kg, i.p., was administered every other day, and ATV in all the three doses was administered daily. Seizure score was continuously monitored until the development of kindling. Thiobarbituric acid reacting species (TBARS), glutathione, dopamine, GABA, and glutamate levels were also assessed in the brain tissues of mice. RESULTS: The results showed that in the ICES test, ATV 80mg/kg increased the seizure threshold to hind limb extension (HLE), and a complete protection against HLE was observed when ATV 80mg/kg was combined with a subanticonvulsant dose of phenytoin. Atorvastatin in all the tested doses suppressed the development of kindling, reduced lipid peroxidation, and increased glutathione levels. All doses of ATV maintained the normal levels of glutamate, GABA, and dopamine in kindled mice. CONCLUSION: Atorvastatin possesses anticonvulsant activity against electroconvulsions. It was found to suppress the development of PTZ kindling, presumably altering the redox status and hippocampal levels of dopamine, glutamate, and GABA.

Prevalence of depression in patients with type 2 diabetes attending an outpatient clinic in India.

BACKGROUND: Clinical studies have suggested that depression is common among patients with type 2 diabetes (T2D). Depression is an important factor which affects the management and complications of diabetes. However, the available data regarding its prevalence in India are limited. OBJECTIVES: To estimate the prevalence of depression in patients in India with T2D and to compare it with a non-diabetic group; and to determine the association of depression with glycaemic control and complications of diabetes in patients with T2D. METHODS: This case-control study was carried out over 5 months from May to September 2012 at a tertiary care hospital in India. Cases were patients with T2D and controls were individuals without diabetes. Depression was assessed using the Patient Health Questionnaire (PHQ)-9. The sociodemographic profile, duration of diabetes, presence of complications and other medical variables were also analysed. RESULTS: 260 subjects of Indian origin (162 men and 98 women; 130 with known T2D and 130 controls without T2D) were evaluated. The prevalence of depression in subjects with T2D was almost twice that in control subjects (46/130 (35.38%) vs 26/130 (20%); p=0.006). A statistically significant difference was found in the fasting blood glucose levels of subjects with depression and those without depression among the patients with T2D (145.70±53.92 vs 130.61±42.39; p=0.022), but depression was not found to be associated with any of the diabetic complications and glycaemic control. CONCLUSIONS: Our findings demonstrate that there is a higher prevalence of depression in Indian patients with T2D, which is almost twice that in those without T2D. Since patients with T2D are at higher risk of developing depression, assessment of depression should be performed as part of the routine practice in India. TRIAL REGISTRATION NUMBER: CTRI/2012/06/002747.

Liposomal formulation of curcumin attenuates seizures in different experimental models of epilepsy in mice.

Contemporary research indicates promising anticonvulsant effect of curcumin. However, its poor oral bioavailability is a major hindrance toward its pharmacological action. Thus, this study was carried out to evaluate the acute effect of liposome-entrapped curcumin on increasing current electroshock seizures (ICES) test, pentylenetetrazole (PTZ)-induced seizures, and status epilepticus in mice. Liposome-entrapped curcumin in doses 25 and 50 mg/kg demonstrated significant increase in seizure threshold current and latency to myoclonic and generalized seizures in ICES test and PTZ-induced seizures, respectively. Similarly, liposomal-entrapped curcumin also increased the latency to the onset and decreased the duration of seizures during status epilepticus in mice. To conclude, liposomal-entrapped curcumin possesses anticonvulsant activity against status epilepticus in mice.

Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice.

Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants viz. lamotrigine (5mg/kg, p.o.), oxcarbazepine (15mg/kg, p.o.) and topiramate (10mg/kg, p.o.) on cognitive function and oxidative stress during pentylenetetrazole (PTZ)-kindling in mice. Kindling was induced by the administration of PTZ (25mg/kg, i.p.) on every alternate day till 5 weeks. Cognition was assessed after the development of kindling. Elevated plus maze (EPM) and passive avoidance response (PAR) tests were carried out after 24h and 48h of the last PTZ administration. After completion of behavioural tests malondialdehyde (MDA), glutathione levels, superoxide dismutase and catalase activity were measured as an indicator of oxidative stress. The results of the present study indicate that topiramate (10mg/kg) administration to kindled animals increased transfer latency and decreased step-down latency in EPM and PAR tests, respectively. However, lamotrigine and oxcarbazepine did not alter the two parameters. Topiramate administration to kindled as well as non-kindled animals has shown increase in MDA and decrease in glutathione levels. Lamotrigine and oxcarbazepine did not show significant alteration in oxidative stress parameters. To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer.

Modulation of pentylenetetrazole-induced kindling and oxidative stress by curcumin in mice.

Epilepsy is a chronic neurological disorder affecting 1% population worldwide. A number of experimental studies have reported anticonvulsant, neuroprotective and antioxidant activity of certain natural products like curcumin, an active ingredient of turmeric. The present study was designed to explore the effect of acute administration of curcumin at doses 50, 100 and 200 mg/kg, orally (p.o.) pentylenetetrazole-induced kindling in mice. Further two oxidative stress markers viz., malondialdehyde (MDA) and glutathione were estimated in brain tissues of rodents. Curcumin (50, 100 and 200 mg/kg, p.o.) dose dependently suppressed the progression of kindling in mice. In addition, the increased levels of MDA and glutathione were also reduced by curcumin in kindled animals. These results suggest that curcumin appears to possess protective activity against kindling in mice.