A Systematic Review on Interferon Alpha-Induced Cognitive Impairment in Hepatitis C Patients.

OBJECTIVE: Interferon-alpha (IFN-α) is an important treatment modality for the hepatitis C virus (HCV). However, treatment with IFN-α is often associated with cognitive difficulties in HCV patients. Thus, this systematic review was performed to assess the effects of IFN-α on cognitive functioning in patients suffering from HCV. METHODS: Relevant literature was identified by performing a comprehensive literature search in major databases including PubMed, clinicaltrials.gov, and Cochrane Central using a combination of suitable keywords. We retrieved studies that were published from the start of each database until August 2021. RESULTS: Out of 210 articles, 73 studies were selected after removing the duplicates. In the first pass, 60 articles were excluded. Out of 13 full-text articles, only 5 articles qualified for qualitative analyses in the second pass. We observed conflicting results concerned with the use of IFN-α and the risk of neurocognitive impairment in HCV patients. CONCLUSION: In conclusion, we have observed conflicting results regarding the impact of INF-α treatment on the cognitive functioning of patients suffering from HCV. Thus, there is an urgent need for an extensive study to evaluate the exact association between INF-αtherapy and cognitive functioning in HCV patients.

Role of Cytokines in Chemotherapy-related Cognitive Impairment of Breast Cancer Patients: A Systematic Review.

BACKGROUND: Cognitive impairment is one of the most common problems experienced by patients receiving chemotherapy, and evidence suggests that cytokines might play an important role. Various studies were conducted to evaluate the role of cytokines in chemotherapy-related cognitive impairment (CRCI). However, the association between CRCI due to cytokines is not well-established. Thus, this systematic review aims to assess the role of cytokines in CRCI in breast cancer patients. METHODS: This systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. An intense literature search was carried out for inclusion criteria in major databases, including PubMed and Clinicaltrials.gov, in August 2021. Studies assessing cognitive parameters through objective and subjective assessment in breast cancer patients receiving chemotherapy were included. RESULTS: A total of 4052 studies were identified, and 15 studies were included in this systematic review. We found that IL-6, IL-1ß, and TNF-α were associated with varying degrees of cognitive impairment in breast cancer patients receiving chemotherapy. CONCLUSION: This systematic review showed a correlation between various cytokines and chemotherapy- associated cognitive decline in breast cancer patients.

Zolpidem use and risk of suicide: A systematic review and meta-analysis.

INTRODUCTION: Zolpidem is one of the most commonly prescribed nonbenzodiazepine hypnotic drugs for insomnia. Published epidemiological studies linked zolpidem with the risk of suicide. However, to date, no meta-analysis investigated this association. Hence, we systematically reviewed and meta-analysed the current evidence from real-world studies reporting the risk of suicide with the use of zolpidem. METHODS: Medline (Ovid), Embase (Ovid), and PsycINFO databases were searched from inception till June 2021 for real-world evidence studies reporting the risk of suicide with the use of zolpidem. The quality assessment of included studies was assessed using the New-Castle Ottawa Scale (NOS). Random-effect meta-analysis was performed using a generic inverse variance method. RESULTS: This meta-analysis was based on four studies with 344,753 participants, of which 42,279 were zolpidem users. The methodological quality of all the included studies was of high quality. A significantly increased risk of suicide or suicide attempt was found in zolpidem users compared to non-users, with a pooled relative risk of 1.88 (95% CI: 1.54 - 2.30). Furthermore, an increased risk of suicidal death was observed in zolpidem users compared to non-users, with a pooled relative risk of 1.82 (95% CI: 1.43 - 2.30). Dose-response analysis also revealed a significantly increased risk of suicide in patients receiving ≥ 180cDDD (cumulative defined daily doses) of zolpidem (124 times), followed by 90-179cDDD (113 times) and <90cDDD (93 times) of zolpidem compared to non-users. CONCLUSION: In conclusion, zolpidem use was associated with an increased risk of suicide or suicide attempt and suicidal death. Therefore, careful prescribing practices must be followed by considering the risk-benefit profile.

Elevated urinary IL-36α and IL-18 levels are associated with diabetic nephropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Inflammatory cytokines have been reported to be pathogenic factors for the development and progression of diabetic nephropathy (DN). Interleukin (IL)-36α is a newly discovered member of the IL-1 cytokine family that has been implicated in animal models of renal impairment. However, little is known about the role of IL-36α in DN in humans. The purpose of the present study was to assess the levels of IL-36α and IL-18 in type 2 diabetic patients (T2DM) patients with and without DN. METHODS: Subjects were divided into 3 groups: Control (N.=20), T2DM without DN (N.=30), and T2DM with DN (N.=30). Urinary IL-36α and IL-18 levels were assessed using ELISA. Correlation analysis was performed to determine the association of the IL levels with clinical markers of T2DM and DN. RESULTS: IL-36α and IL-18 levels were significantly elevated in T2DM patients with DN, when compared to T2DM patients without DN (P<0.0001, P=0.0025, respectively) and controls (P<0.0001, for both). IL-36α levels showed a positive correlation with urinary albumin excretion (r=0.754, P<0.0001), HbA1c (r=0.433, P=0.0168), fasting plasma glucose (r=0.433, P=0.0168) and negative correlation with glomerular filtration rate (r=-0.852 P<0.0001). CONCLUSIONS: The results highlighted the association of IL-36α with DN. However, further extensive studies are suggested for evaluating the association.

Risk Factors for Hematopoietic Stem Cell Transplantation-Associated Bone Loss.

Hematopoietic stem cell transplantation (HSCT), including bone marrow transplantation, is the treatment of choice for many hematologic diseases, including hematologic malignancies and different types of anemia. The use of HSCT is increasing annually, mainly because advanced research that has been conducted in this area has exponentially expanded the indications for HSCT and significantly improved transplantation techniques and supportive care practices. Collectively, these improvements have led to an increase in the overall survival of HSCT patients. However, as post-HSCT survival is increasing, awareness of the potential late complications of HSCT is also growing. Unpredictable bone loss is one of the major post-HSCT complications that can cause significant morbidity and impair the quality of life of survivors. Although the exact mechanism of post-HSCT bone loss is not yet known, previous studies have suggested that numerous factors, including destructive preparative regimens (eg, high-dose chemotherapy, total body irradiation), treatment-related complications (eg, graft-versus-host disease), endocrine abnormalities (eg, diabetes mellitus, thyroid dysfunction, adrenal insufficiency), lack of physical activity, and the underlying disease itself are responsible for HSCT-associated bone loss. Sufficient data have been collected to suggest that post-HSCT bone loss can be prevented and treated using the same preventive and treatment modalities as used for the general population. Various guidelines have been formulated to help keep a check on HSCT recipients' deteriorating bone health.

Liquid Crystalline Nanoparticles for Nasal Delivery of Rosuvastatin: Implications on Therapeutic Efficacy in Management of Epilepsy.

In the present study we investigated the protective role of intranasal rosuvastatin liquid crystalline nanoparticles (Ros-LCNPs) against pentylenetetrazole (PTZ) induced seizures, increasing current electroshock (ICES) induced seizures, and PTZ-induced status epilepticus. From the dose titration study, it was evident that intranasal rosuvastatin (ROS), at lower dose, was more effective than oral and intraperitoneal ROS. The Ros-LCNPs equivalent to 5 mg/kg ROS were developed by hydrotrope method using glyceryl monooleate (GMO) as lipid phase. The high resolution TEM revealed that the formed Ros-LCNPs were cubic shaped and multivesicular with mean size of 219.15 ± 8.14 nm. The Ros-LCNPs showed entrapment efficiency of 70.30 ± 1.84% and release was found to be biphasic following Korsmeyer-Peppas kinetics. Intranasal Ros-LCNPs (5 mg/kg) showed significant increase in latency to PTZ-induced seizures and ICES seizure threshold compared to control and intranasal ROS solution. Additionally, intranasal Ros-LCNPs provided effective protection against PTZ-induced status epilepticus. No impairment in cognitive functions was observed following intranasal Ros-LCNPs. The results suggested that Ros-LCNPs could be an effective and promising therapeutics for the epilepsy management.

Increased serum interleukin-9 and interleukin-1ß are associated with depression in type 2 diabetes patients.

BACKGROUND: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. OBJECTIVE: The aim of the present study was to investigate depression and its association with interleukins (IL)-1ß and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. METHODS: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1ß and IL-9 were measured in serum samples of all the patients using ELISA kit. RESULTS: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1ß were elevated in Group 3, as compared to the other groups. CONCLUSION: This study showed positive association between depression and IL-1ß, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.

Increased serum interleukin-9 and interleukin-1β are associated with depression in type 2 diabetes patients / Interleucina-9 e interleucina-1β séricas aumentadas estão associadas à depressão em pacientes com diabetes tipo 2

ABSTRACT Background: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. Objective: The aim of the present study was to investigate depression and its association with interleukins (IL)-1β and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. Methods: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1β and IL-9 were measured in serum samples of all the patients using ELISA kit. Results: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1β were elevated in Group 3, as compared to the other groups. Conclusion: This study showed positive association between depression and IL-1β, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.

RESUMO Introdução: O diabetes e a depressão comórbidas são condições crônicas prevalentes que afetam negativamente a qualidade de vida (QdV). A inflamação tem sido considerada como um mecanismo integral em pacientes com diabetes e depressão. Objetivo: Investigar a depressão e sua associação com interleucinas (IL)-1β e IL-9 em pacientes diabéticos tipo 2 (DM2) e controles. A QdV em diabéticos também foi avaliada. Métodos: Foram incluídos 80 indivíduos, divididos em três grupos: Grupo 1 - controles saudáveis; Grupo 2 - pacientes com DM2 sem depressão; Grupo 3 - pacientes com DM2 com depressão. A depressão e a QdV foram avaliadas usando o Questionário de Saúde do Paciente (Patient Health Questionnaire - PHQ-9) e a auditoria de QdV dependente de diabetes (Audit of Diabetes-Dependent Quality of Life - ADDQoL), respectivamente. IL-1β e IL-9 foram medidas em amostras de soro de todos os pacientes utilizando kit de ELISA. Resultados: O escore do PHQ no grupo 3 foi significativamente maior em comparação ao grupo 1. Os escores de ADDQoL no grupo 3 foram significativamente maiores em comparação ao grupo 2. Os níveis de IL-9 e IL-1β foram elevados no grupo 3, como em comparação com os outros grupos. Conclusão: Este estudo mostrou associação positiva entre depressão e IL-1β, IL-9 em pacientes com DM2. Além disso, os pacientes diabéticos têm pior QdV, o que é ainda piorado pela presença de depressão. Assim, a avaliação rotineira da presença de depressão é sugerida em pacientes com DM2.

Study of Awareness and Practice of Informed Consent Process Among Clinical Trial Participants and Their Motives Behind Participation.

Process to obtain informed consent is an essential component in research involving human subjects. However, much is not known about the level of awareness participants have about optimal consenting process and the motives that drive their participation in the trials. A cross-sectional study was conducted among volunteers who had been participating in clinical trials in contract research organizations of Delhi. Validated questionnaires were used to assess their knowledge, attitude, and practice of informed consent process. Most of the volunteers, 226 (56.5%), had participated in 1 to 3 clinical trials. Majority (54%) were unaware about any informed consent document. None of them were aware of their right of profession competence, privacy and integrity, transparency, nonexploitation, and nonusage of their biological samples. Effective implementation of principles of informed consenting is largely lacking among contract research organizations in Delhi, India. This could potentially cause risk to the participants.

Intranasal pitavastatin attenuates seizures in different experimental models of epilepsy in mice.

This study was carried out to evaluate the effect of intranasal pitavastatin (PVS) on pentylenetetrazole (PTZ)-induced seizures, increasing current electroshock (ICES) seizures, and status epilepticus in mice. Intranasal PVS, 0.5 and 1.0mg/kg, showed significant increase in latency to PTZ-induced seizures and ICES seizure threshold compared to control; however, the effects were dose-dependent and were more significant at higher dose. Further, intranasal PVS (1.0mg/kg) but not intravenous PVS (50.0mg/kg) showed effective protection against PTZ-induced status epilepticus. No impairment in cognitive functions was observed following intranasal PVS (1.0mg/kg), thus making it a prospective therapeutic approach for acute seizures and status epilepticus.

Effects of agomelatine on pentylenetetrazole-induced kindling, kindling-associated oxidative stress, and behavioral despair in mice and modulation of its actions by luzindole and 1-(m-chlorophenyl) piperazine.

In view of well-evidenced antiepileptic effects of melatonin and few reports of anticonvulsant action of agomelatine, the present study investigated whether agomelatine protects against pentylenetetrazole (PTZ)-induced kindling in mice and kindling-associated oxidative stress, depression, and impairment of spatial memory. In order to explore whether effects are mediated by melatonergic or serotonergic mechanisms, 1-(m-chlorophenyl) piperazine (mCPP), selective 5HT2c receptor agonist and luzindole, melatonergic receptor antagonist, were taken as pharmacological tools. In view of few hepatotoxic reports on agomelatine, the study evaluated effects on hepatic enzyme levels. Swiss strain albino mice were injected with PTZ (25mg/kg, i.p.) once every two days for 5weeks to induce kindling. The effects of agomelatine (10mg/kg, p.o.) alone and in combination with luzindole (2.5mg/kg, i.p.) or mCPP (7mg/kg, i.p.) on seizure severity during induction and % incidence of animals kindled at the end of 5weeks were recorded. Modified forced swim test was used for studying depression-like behavior while spontaneous alternation behavior was used for studying effects on spatial memory. Serum AST and ALT concentrations, cortical and hippocampal malondialdehyde, and reduced glutathione were measured. Agomelatine 10mg/kg, p.o. effectively delayed development of kindling, reduced seizure severity, and decreased % incidence. Luzindole reversed the protective effects of agomelatine while mCPP failed to show such a reversal, indicating melatonergic (and not serotonergic) mechanisms in the observed effects. Agomelatine also showed antioxidant effects that can partially contribute to its anticonvulsant action. In addition, it alleviated PTZ-kindling-associated behavioral despair and favorably modulated liver enzymes. Its effects on improvement of kindling-associated spatial memory could possibly be related to its effects on locomotor activity. Agomelatine, thus, could be explored as an adjunct to antiepileptic drugs for seizure control and for alleviating epilepsy-associated depression.

Alteration of Thyroid Function in Indian HER 2-Negative Breast Cancer Patients Undergoing Chemotherapy.

BACKGROUND: Thyroid hormones (TH) are regulated by the hypothalamic-pituitary axis, which plays an important role in cell growth, differentiation, development and other aspects of metabolism. It is believed that an active hypothalamic-pituitary axis increases the susceptibility of thyroid dysfunction during systemic chemotherapy. In order to investigate the relation between thyroid function and chemotherapy the present study was designed to investigate TH in breast cancer patients receiving at least three cycles of chemotherapy. The levels of TH were measured at the baseline and before each cycle of chemotherapy. MATERIALS AND METHODS: Blood samples for estimation of TH levels were collected from 80 (pre-menopausal-40; post-menopausal-40) breast cancer patients just before they were undergoing--1st, 2nd, 3rd and 4th cycle of chemotherapy. The serum was separated and T3, T4 and TSH levels were determined by chemiluminescence method. RESULTS: T3 and T4 were found significantly decreased and TSH was found significantly increased after 1st (p<0.001), 2nd (p<0.0001) and 3rd cycle of chemotherapy (p<0.0001). The variation of T3 levels (decreased) and TSH levels (increased) was found more in post-menopausal (p<0.0001) women then in pre-menopausal women after 3rd cycle of chemotherapy as compared to baseline (p<0.001). CONCLUSIONS: TH were remarkably altered after each cycle of chemotherapy leading to decline in thyroid function of breast cancer patients. Further, the results also indicated that post- menopausal women were more prone towards decline in thyroid function then pre-menopausal women. The present study proposes the monitoring of TH after each cycle of chemotherapy in breast cancer patients.