Prognostic significance of metastasis-associated protein S100A4 (Mts1) in prostate cancer progression and chemoprevention regimens in an autochthonous mouse model.

PURPOSE: We recently showed that metastasis-promoting Mts1 gene (S100A4) and protein is overexpressed during progression of prostate cancer in humans. The purpose of this study was to assess the expression of S100A4 during autochthonous prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Because oral consumption of green tea polyphenols (GTP) has been shown to inhibit metastasis and prostate cancer in TRAMP, we further assessed the significance of S100A4 during chemoprevention regimen. EXPERIMENTAL DESIGN: Male TRAMP mice 8 weeks of age were equally divided into two groups. A freshly prepared 0.1% GTP solution in tap water was supplied thrice a week to experimental animals as the sole source of drinking fluid for 24 weeks, whereas the control group of animals received the same tap water throughout the experiment. The animals were sacrificed at 0, 8, 16, and 24 weeks of GTP feeding and were analyzed for S100A4 and E-cadherin. Additional untreated and treated nontransgenic controls were also included in the study. RESULTS: With the progression of age and prostate cancer growth in TRAMP mice, an increase in the expression of S100A4 at mRNA and protein level in dorsolateral prostate, but not in nontransgenic mice, occurred. GTP feeding to TRAMP mice resulted in marked inhibition of prostate cancer progression, which was associated with reduction of S100A4 and restoration of E-cadherin. CONCLUSIONS: S100A4 represents a promising marker for prostate cancer progression and could be employed as a biomarker in chemoprevention regimens.     

Valproate attenuates dextroamphetamine-induced subjective changes more than lithium

Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n = 12), 900 mg lithium (n = 9), or placebo (n = 12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of dextroamphetamine, and at two time points after administration. Differences in the response to dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.     

Development and evaluation of osmotically controlled oral drug delivery system of glipizide.

Extended release formulation of glipizide based on osmotic technology was developed and evaluated. The effect of different formulation variables, namely, level of solubility modifier in the core, membrane weight gain, and level of pore former in the membrane, were studied. Drug release was found to be affected by the level of solubility modifier in the core formulation. Glipizide release was inversely proportional to the membrane weight but directly related to the initial level of pore former (PVP) in the membrane. Burst strength of the exhausted shells increased with the weight gain of the membrane. On the other hand, burst strength decreased with an increase in the level of pore former in the membrane. Drug release from the developed formulations was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Results of SEM studies showed the formation of pores in the membrane from where the drug release occurred. The numbers of pores were directly proportional to the initial level of pore former in the membrane. The manufacturing procedure was found to be reproducible and formulations were stable after 3 months of accelerated stability studies.     

Impaired anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with diabetes mellitus: A preliminary report

Background and aimsPatients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM).MethodsRecords of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis.ResultsThirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA_1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14–17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019).ConclusionsCOVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.     

Cannabis/Cannabinoids for Treating COVID-19 Associated Neuropsychiatric Complications

COVID-19 epidemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health effects that have included respiratory/pulmonary, cardiovascular, mental health and neurological consequences such as anxiety, depression, and substance use. Several effective vaccines have been developed and extensive efforts are underway to develop therapeutics to treat COVID-19. Cannabis and/or its product-cannabidiol (CBD) are being advertised for the treatment of COVID-19 associated mental/neurological complications and substance use disorders. However, research reviewed shows that there is insufficient data from clinical studies to support the use of cannabis or CBD for the treatment of COVID-19 associated mental health and neurological complications. Additional basic and clinical research is suggested to develop cannabis or cannabidiol for the treatment of mental health problems associated with coronavirus infection and or substance use disorders. In the meantime, it is important that the addiction physician/psychiatrist must caution while prescribing or recommending cannabis or CBD for treating such clinical indications.

Graphical abstract

Research shows that currently there is no clinical evidence to support the use of cannabis or any of its compounds including CBD for treating any of the neuropsychiatric complications of COVID-19. Thus, it is important that the addiction physicians/psychiatrists caution their patients from using cannabis or cannabis products for treating any such complications.