Design and evaluation of oral nanoemulsion drug delivery system of mebudipine

Abstract

A nanoemulsion drug delivery system was developed to increase the oral bioavailability of mebudipine as a calcium channel blocker with very low bioavailability profile. The impact of nano-formulation on the pharmacokinetic parameters of mebudipine in rats was investigated. Nanoemulsion formulations containing ethyl oleate, Tween 80, Span 80, polyethylene glycol 400, ethanol and deionized water were prepared using probe sonicator. The optimum formulation was evaluated for physicochemical properties, such as particle size, morphology and stability. The particle size of optimum formulation was 22.8?±?4.0?nm. Based on the results of this study, the relative bioavailability of mebudipine nanoemulsion was enhanced by about 2.6-, 2.0- and 1.9-fold, respectively, compared with suspension, ethyl oleate solution and micellar solution. In conclusion, nanoemulsion is an interesting option for the delivery of poorly water soluble molecules, such as mebudipine.     

The impact of a randomized dietary and physical activity intervention on chronic inflammation among obese African-American women

ABSTRACT

Lifestyle interventions may reduce inflammation and lower breast cancer (BrCa) risk. This randomized trial assessed the impact of the Sistas Inspiring Sistas Through Activity and Support (SISTAS) study on plasma C-reactive protein (CRP), interleukin-6 (IL-6) and Dietary Inflammatory Index (DII). This unblinded, dietary and physical activity trial was implemented in 337 obese (body mass index [BMI] ≥30 kg/m²) African American (AA) women recruited between 2011 and 2015 in South Carolina through a community-based participatory approach with measurements at baseline, 3 months, and 12 months. Participants were randomized into either intervention (n = 176) or wait-list control group (n = 161). Linear mixed-effect models were used for analyses of CRP and IL-6. Baseline CRP was significantly higher in those with greater obesity, body fat percentage, and waist circumference (all p <.01). No difference was observed between groups for CRP or IL-6 at 3 or 12 months; however, improvements in diet were observed in the intervention group compared to the control group (p = .02) at 3 months but were not sustained at 12 months. Although the intervention was not successful at reducing levels of CRP or IL-6, a significant decrease was observed in DII score for the intervention group, indicating short-term positive dietary change.     

Presynaptic α₂-adrenoceptors control the inhibitory action of presynaptic CB₁ cannabinoid receptors on prefrontocortical norepinephrine release in the rat

Endocannabinoids play a crucial neuromodulator role in both physiological and pathological states in various brain regions including the prefrontal cortex (PFC). We examined, whether presynaptic cannabinoid receptors are involved in the modulation of basal and electrical field stimulation-evoked [³H]norepinephrine ([³H]NE) release from rat PFC slices. WIN55,212-2, a nonselective CB₁ receptor (CB₁R) agonist, inhibited the electrical stimulation-evoked efflux of [³H]NE in a concentration-dependent fashion, which was antagonized by the CB₁R antagonist/inverse agonist, AM251 (1 μM). Idazoxan, a selective α₂-adrenoceptor antagonist, augmented the evoked [³H]NE release. In the presence of idazoxan, the effect of WIN55,212-2 was exacerbated or attenuated, depending on the applied concentration and stimulation frequency. Moreover their combined, but not individual application elicited a depressive-like phenomenon in the forced-swim test. These data were bolstered with fluorescent and confocal microscopy analysis, which revealed that CB₁R immunoreactivity co-localized with dopamine-β-hydroxylase positive (i.e. noradrenergic) fibers and the inhibitory α_2A adrenergic autoreceptors (α_2AR) in the PFC. Furthermore, idazoxan triggered a decrease in CB₁R density in the PFC, suggesting that high extracellular level of norepinephrine downregulates CB₁Rs.     

The Role of School Health Centers in Health Care Access and Client Outcomes

Objectives. We describe the impact of school health centers in Alameda County, California, on adolescents'' access to care and their mental and physical health outcomes.Methods. We used a multimethod evaluation of 12 school health centers to track data on clients (n = 7410), services, and provider-reported outcomes; client pre–post surveys (n = 286); and student focus groups (n = 105 participants).Results. School health centers were the most commonly reported source of medical (30%), family planning (63%), and counseling (31%) services for clients. Mental health providers reported significant improvements (P < .05) from baseline to follow-up in clients'' presenting concerns and resiliency factors. Medical providers and clients also reported general improvements in reproductive health, particularly in the use of birth control other than condoms. Student focus group participants noted that school health centers helped improve access to services students might not seek out otherwise, particularly counseling and family planning services. Furthermore, students noted that they liked school health centers because of their confidentiality, free services, convenience, and youth-friendly staff.Conclusions. School health centers increase access to care and improve mental health, resiliency, and contraceptive use.School-based and school-linked health centers (hereafter “school health centers”) represent a model of care that responds to the unique physical and mental health issues of adolescents by offering care in an accessible, youth-friendly environment. Studies have found that access to school health centers increases use of primary care, reduces use of emergency rooms, and results in fewer hospitalizations.^1–3 School health centers also expand access to and quality of care for underserved adolescents; one study found that school health center users were more likely than were traditional outpatient clients to have received primary and preventive care services despite the fact that they were less likely to be insured.⁴ Furthermore, adolescents with alternate forms of health care report high degrees of comfort-seeking care at school health centers.⁵Adolescent mental health outcomes have also improved because of school health centers. Studies have shown a significant decline in depression among students who received school health center mental health services⁶ and a reduced likelihood of suicide ideation among students attending schools with school health centers.⁷ Studies have also documented the positive impact of school health centers on reproductive health outcomes,⁸ including improved contraceptive use.⁹Although research has demonstrated how the school health center model of care can affect health access and outcomes, many studies have been limited by relatively small sample sizes. Collecting uniform outcome data from larger coalitions of school health centers is challenging, given the obstacles of different school districts, community health providers, service structures, and data confidentiality regulations. Our aim was to demonstrate the impact of 12 school health centers on clients'' access to care, satisfaction, and reproductive and mental health outcomes. We incorporated data collection from both client and provider perspectives through a standardized evaluation process that documents services provided, as well as provider assessments of 2 outcome measures that school health centers have been known to affect: reproductive health and mental health.     

Severe Acute Respiratory Syndrome Coronavirus 2 Seropositivity among Healthcare Personnel in Hospitals and Nursing Homes,Rhode Island,USA, July–August 2020

Healthcare personnel are recognized to be at higher risk for infection with severe acute respiratory syndrome coronavirus 2. We conducted a serologic survey in 15 hospitals and 56 nursing homes across Rhode Island, USA, during July 17–August 28, 2020. Overall seropositivity among 9,863 healthcare personnel was 4.6% (95% CI 4.2%–5.0%) but varied 4-fold between hospital personnel (3.1%, 95% CI 2.7%–3.5%) and nursing home personnel (13.1%, 95% CI 11.5%–14.9%). Within nursing homes, prevalence was highest among personnel working in coronavirus disease units (24.1%; 95% CI 20.6%–27.8%). Adjusted analysis showed that in hospitals, nurses and receptionists/medical assistants had a higher likelihood of seropositivity than physicians. In nursing homes, nursing assistants and social workers/case managers had higher likelihoods of seropositivity than occupational/physical/speech therapists. Nursing home personnel in all occupations had elevated seropositivity compared with hospital counterparts. Additional mitigation strategies are needed to protect nursing home personnel from infection, regardless of occupation.     

Role of Nitric Oxide in Neurodegeneration: Function,Regulation, and Inhibition

Reactive nitrogen species (RNS) and reactive oxygen species (ROS), collectively known as reactive oxygen and nitrogen species (RONS), are the products of normal cellular metabolism and interact with several vital biomolecules including nucleic acid, proteins, and membrane lipids and alter their function in an irreversible manner which can lead to cell death. There is an imperative role for oxidative stress in the pathogenesis of cognitive impairments and the development and progression of neural injury. Elevated production of higher amounts of nitric oxide (NO) takes place in numerous pathological conditions, such as neurodegenerative diseases, inflammation, and ischemia, which occur concurrently with elevated nitrosative/oxidative stress. The enzyme nitric oxide synthase (NOS) is responsible for the generation of NO in different cells by conversion of L-arginine (Arg) to L-citrulline. Therefore, the NO signaling pathway represents a viable therapeutic target. Naturally occurring polyphenols targeting the NO signaling pathway can be of major importance in the field of neurodegeneration and related complications. Here, we comprehensively review the importance of NO and its production in the human body and afterwards highlight the importance of various natural products along with their mechanisms against various neurodegenerative diseases involving their effect on NO production.     

A comparative study between non‑colistin based combinations for treatment of infections caused by extensive drug resistant Acinetobacter baumannii: comments

International Journal of Clinical Pharmacy -     

Cutaneous lupus profundus]

The objective of this studies is to review clinical and laboratory features of lupus panniculitis. The authors report 3 cases of lupus profundus from a group of 70 lupus erythematosus. In both cases the lupus panniculitis presented as subcutaneous infiltrated and indurated nodules. The diagnosis was confirmed on clinical, histological and therapeutic data. The evolution is slow and is characterised by regression of the inflammatory lesions with treatment by antimalarial drugs. The lupus panniculitis has generally a favorable prognosis.     

Chronic Administration of Ketamine Elicits Antidepressant‐Like Effects in Rats without Affecting Hippocampal Brain‐Derived Neurotrophic Factor Protein Levels

Abstract: A growing body of evidence has pointed to the blockade of the N‐methyl‐d ‐aspartate (NMDA) receptor signaling as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open‐field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain‐derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine‐ and ketamine‐treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders.     

Protective effects of L-arginine against cisplatin-induced renal oxidative stress and toxicity: role of nitric oxide

Nephrotoxicity is a dose-limiting factor in clinical use of cisplatin. The changes in renal haemodynamics were suggested to play a role in cisplatin-induced nephrotoxicity. The aim of the present study was to investigate the effect of modulation of nitric oxide on the severity of cisplatin-induced nephrotoxicity using an experimental rat model. A nitric oxide precursor, L-arginine and an inhibitor of nitric oxide synthase, L-NAME were used. After six days of cisplatin injection, acute nephrotoxicity was demonstrated by a marked increase in serum creatinine and blood urea nitrogen. Histological examination of the kidneys confirmed the occurrence of renal damage. Moreover, cisplatin induced an increase in the level of lipid peroxides and oxidized glutathione and a depletion of reduced glutathione. The activities of the antioxidant enzymes glutathione peroxidase and superoxide dismutase were also lowered. Besides, there was a reduction in the kidney total nitrate/nitrite levels. L-arginine significantly attenuated the oxidative stress and nephrotoxic effect of cisplatin. On the other hand, L-NAME was found to aggravate cisplatin nephrotoxicity. In conclusion, the decrease in the kidney nitric oxide level contributes, at least in part, in the mechanism underlying the nephrotoxicity of cisplatin. Furthermore, L-arginine shows nephroprotective effects and might be useful in improving the therapeutic index of cisplatin.