The alprazolam analogue 4'-chloro deschloroalprazolam identified in seized capsules.

New designer benzodiazepines continue to be identified in the illicit drug market. In December 2021, eight capsules were submitted to ChemCentre for analysis. The samples were analysed by a range of analytical techniques including gas chromatography-mass spectrometry (GC-MS), ultraviolet-visible spectrophotometry, liquid chromatography-mass spectrometry (LC-MS, low and high resolution), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, which identified the main component of the capsules to be 4'-chloro deschloroalprazolam, a new designer benzodiazepine. Alarmingly, the mass spectral data for this alprazolam analogue were very similar to that of alprazolam, such that misidentification could be possible. A minor component of the capsules was also partially characterised, it is believed to be the synthetic precursor 4'-chloro deschloronordiazepam. The information provided in this paper includes ways to discriminate these analogues from alprazolam and nordiazepam which will enable other laboratories to identify these new drugs.

Experimental Evidence of Long-Lived Electric Fields of Ionic Liquid Bilayers.

Herein we demonstrate that ionic liquids can form long-lived double layers, generating electric fields detectable by straightforward open circuit potential (OCP) measurements. In imidazolium-based ionic liquids an external negative voltage pulse leads to an exceedingly stable near-surface dipolar layer, whose field manifests as long-lived (∼1-100 h) discrete plateaus in OCP versus time traces. These plateaus occur within an ionic liquid-specific and sharp potential window, defining a simple experimental method to probe the onset of interfacial ordering phenomena, such as overscreening and crowding. Molecular dynamics modeling reveals that the OCP arises from the alignment of the individual ion dipoles to the external electric field pulse, with the magnitude of the resulting OCP correlating with the product of the projected dipole moment of the cation and the ratio between the cation diffusion coefficient and its volume. Our findings also reveal that a stable overscreened structure is more likely to form if the interface is first forced through crowding, possibly accounting for the scattered literature data on relaxation kinetics of near-surface structures in ionic liquids.

Optimization of activated palm oil sludge biochar preparation for sulphur dioxide adsorption.

Palm oil sludge (POS) is an organic waste generated from the palm oil industry. POS causes environmental pollution if it is improperly disposed. In this study, the potential of activated POS biochar, as an adsorbent for the removal of SO2 gas was tested. POS biochar was physically activated using CO2 gas. The effects of activation preparation variables i.e. activation temperature (300-700 °C), activation time (30-150 min) and CO2 flow rate (100-500 ml/min) were investigated using design expert version 8.0.7.1 software. Central Composite Design (CCD) was used to develop a quadratic model to correlate the operating variables with the activated biochar adsorption capacity. Analysis of variance (ANOVA) was performed to identify the significant factors on the experimental design response. The optimum preparation conditions of activated POS biochar were found to be at activation temperature of 442 °C, activation time of 63 min and CO2 flow rate of 397 ml/min. The maximum adsorption capacity at the optimum conditions was recorded as 16.65 mg/g. The adsorption capacity increased significantly after the activation process. Characteristics of the activated POS biochar proposed that SO2 was physically adsorbed. Furthermore, it was found that the adsorption capacity can be further enhanced by increasing the reaction temperature to 100 °C or with 15% of relative humidity in the inlet gas. The prepared adsorbents can be regenerated by thermal treatment.

Adsorptive behaviour of palm oil mill sludge biochar pyrolyzed at low temperature for copper and cadmium removal.

In this work, the influence of pyrolysis temperature on the physicochemical properties of palm oil mill sludge biochar (POSB) and its adsorption properties towards cadmium (Cd) and copper (Cu) was investigated. Characterization experiments suggested that POSBs' surface functional groups play the major role in the adsorption process. POSB pyrolyzed at 400 °C showed the best characteristics for Cu and Cd removal. Adsorption study indicated that contact time and shaking speed enhances the adsorption capacity of POSB. It was affirmed that pH adjustment is not necessary for POSB to adsorb Cu and Cd. Mechanism studies fitted well with Langmuir and Pseudo-Second Order model. Thermodynamic parameters indicated that the adsorption was spontaneous, endothermic and correspond to chemical adsorption. The highest uptakes of Cu and Cd were recorded at 48.8 mg/g and 46.2 mg/g respectively. This work verifies that the temperature used for palm oil mill sludge (POS) pyrolysis and adsorption condition played the most prominent role in Cu and Cd removal from aqueous solutions.

Thermal annealing behaviour and gel to crystal transition of a low molecular weight hydrogelator.

The thermal annealing behaviour of an electrolyte-triggered calixarene hydrogelator is found to depend strongly on the specific metal chloride used. While the lithium chloride gel showed typical gel-sol transitions as a function of temperature, the magnesium chloride gel was found to repeatedly strengthen with heat-cool cycles. Structural investigations using small-angle neutron scattering, and scanning probe microscopy, suggest that the annealing behaviour is associated with a change in morphology of the fibrous structures supporting the gel. On prolonged standing at room temperature, the magnesium chloride gel underwent a gel-crystal transition, with the collapsing gel accompanied by the deposition of crystals of a magnesium complex of the proline-functionalised calix[4]arene gelator.

Investigating hydrogel formation using in situ variable-temperature scanning probe microscopy.

The assembly and disassembly of supramolecular gel fibres are observed in situ using variable temperature scanning probe microscopy. The results show that fibre formation can be monitored at high resolution at a surface, and the final fibre morphologies are broadly consistent with those found by ex situ analysis of the bulk gel. The impact of a gelation inhibitor upon the fibre morphology is successfully investigated, providing direct evidence for the mechanism of inhibition as a function of additive concentration.

Cardiorenal syndrome type 4: a review.

There is a bidirectional and complex relationship between the heart and kidneys. This interaction is physical, chemical as well as biological and is also reflected in a strong connection between renal and cardiovascular diseases. Cardiorenal syndrome type 4 (CRS type 4) is characterized by primary chronic kidney disease (CKD) leading to an impairment of cardiac function, with ventricular hypertrophy, diastolic dysfunction, and/or increased risk of adverse cardiovascular events. The incidence of CKD is increasing, and CRS type 4 is becoming a major public health problem associated with a high morbidity and mortality. In this study, we briefly review the epidemiology and pathophysiology of CRS type 4, the role of biomarkers in its early identification, and its management.

Renal replacement therapies for prevention of radiocontrast-induced nephropathy: a systematic review.

BACKGROUND: Radiocontrast-induced nephropathy (RCIN) is an important cause of acute kidney injury, increasing in-hospital and long-term mortality. It is controversial whether prophylactic renal replacement therapy (RRT) may reduce a patient's risk of RCIN when compared with standard medical therapy (SMT). METHODS: We searched through PubMed and bibliographies of retrieved articles. Published studies of RRT for RCIN prevention in patients receiving radiocontrast were included. The primary endpoint was RCIN incidence, defined as an increase in serum creatinine ≥0.5 mg/dL. Results were combined on the risk ratio (RR) scale. Random-effects models were used. Sensitivity analyses were defined a priori to evaluate the effects of RRT modality, study design, and sample size. RESULTS: Nine randomized controlled and 2 nonrandomized trials were included (n = 1010 patients); 8 studies used hemodialysis (HD) and 3 used hemofiltration or hemodiafiltration. Nine studies had data for primary endpoint; RCIN incidence was 23.3% in the RRT group and 21.2% in SMT. RRT did not decrease RCIN incidence compared with SMT (risk ratio [RR] 1.02; 95% confidence interval [CI], 0.54-1.93); however, intertrial heterogeneity was high. In sensitivity analyses, limiting to only HD studies significantly reduced heterogeneity. HD appeared to increase RCIN risk (RR 1.61; 95% CI, 1.13-2.28) and had no effect on need for permanent RRT or progression to end-stage renal disease (RR 1.47; 95% CI, 0.56-3.89). CONCLUSION: In this updated meta-analysis, periprocedural RRT did not decrease the incidence of RCIN compared with SMT. HD appears to actually increase RCIN risk.

Cardiorenal syndrome: a complex series of combined heart/kidney disorders.

Over the last decade, it has become increasingly clear that the cardiovascular and renal systems are interdependent. Primary disorders of either system have been shown to disturb the other system. As a result, a class of cardiorenal syndrome (CRS) has been identified where in a vicious cycle is established in which acute/chronic dysfunction of either the kidney or the heart exacerbates the loss of function in the other organ. The ADQI organization has proposed a classification derived from a consensus conference held in 2008. CRS is classified as a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other. The general definition has been expanded into five subtypes: CRS type 1 = acute worsening of heart function (acute heart failure-acute coronary syndrome) leading to kidney injury and/or dysfunction; CRS type 2 = chronic abnormalities in heart function (chronic heart failure-chronic heart disease) leading to kidney injury or dysfunction; CRS type 3 = acute worsening of kidney function (acute kidney injury) leading to heart injury and/or dysfunction; CRS type 4 = chronic kidney disease (chronic kidney disease) leading to heart injury, disease and/or dysfunction; and CRS type 5 = systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. A major problem with previous terminology was that it did not allow for identification of pathophysiological interactions occurring in the different types of combined heart/kidney disorders. The subdivision into different subtypes seems to provide a better approach to this syndrome.

Self-inclusion of proline-functionalised calix[4]arene leads to hydrogelation.

Solution-phase and solid-state structural studies indicate that the remarkable hydrogelation properties of a proline-functionalised calix[4]arene emerge as a result of extended helical structures formed via inclusion of a proline moiety in a neighbouring calixarene cavity.

Laboratory parameters of cardiac and kidney dysfunction in cardio-renal syndromes.

"Cardio-Renal Syndromes" (CRS) are disorders of the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The pathophysiology of CRS is complex, and there is accumulating evidence that various novel biomarkers are useful for diagnosis, prognostication, and risk stratification in patients with heart failure and chronic kidney disease (CRS). When both the heart failure (HF) and CKD occur together, it is important to have biomarkers that are able to risk stratify patients by looking at both their heart and kidney aspects. There are some promising newer renal biomarkers that may contribute to a better evaluation and prediction of prognosis in CRS patients. Most of the renal biomarkers studies in CRS have been performed in the setting of cardiac surgery, acute coronary syndrome (ACS), HF or after exposure to radiocontrast media in diagnostic and/or therapeutic percutaneous coronary procedures. Natriuretic peptides (NPs) have been validated as an important cardiac biomarker for risk stratification and prognostication in HF patients with or without CKD. However, the best cutoff values for each stage of CKD, including those on renal replacement therapy, are yet to be ascertained. In this context, it is likely that panels of multiple biomarkers will be needed for optimal evaluation, risk stratification, timely treatment initiation, and follow-up of patients with CRS.

Enhancement of solute removal in a hollow-fiber hemodialyzer by mechanical vibration.

Better solute clearance, particularly of middle-molecular-weight solutes, has been associated with improved patient outcomes. However, blood-membrane interaction during dialysis results in the development of secondary mass transfer resistances on the dialyzer membrane surface. We discuss the potential effects of mechanical vibration on the diffusion, convection and adsorption of uremic solutes during dialysis. For sinusoidal and triangular vibratory motions, we conceptualized the hemodynamic changes inside the membrane and consequent effects on membrane morphology. Longitudinal vibration generates reverse flow by relative membrane motion, and transverse vibration generates a symmetric swirling flow inside the hollow fiber, which enhances wall shear stress and flow mixing. Moreover, the impulse induced by triangle wave vibration could provide higher absorption capacity to middle-molecular-weight solutes. Mechanical vibration could enhance solute removal by minimizing membrane morphology changes resulting from blood-membrane interaction during hemodialysis. These effects of mechanical vibration can be helpful in extracorporeal blood purification therapies including continuous, portable and wearable systems.

Early biomarkers of renal injury.

Cardiorenal syndrome (CRS) refers to pathophysiologic interaction of the heart and kidney and is associated with acute kidney injury (AKI) and high mortality. Cardiac surgery or acute decompensated heart failure and radiocontrast-induced nephropathy are common clinical scenarios of CRS. Unfortunately, established functional biomarkers of glomerular filtration rate such as serum creatinine, urea, and diuresis delay AKI diagnosis by 24 to 48 hours. Novel renal biomarkers indicating tubular injury are emerging and may have wide implications. This review focuses on several novel renal biomarkers with the most promising biologic characteristics and clinical evidence for their AKI predictive ability: neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin 18, and fatty acid-binding proteins. The value of each biomarker is reviewed on currently available clinical data in typical settings of CRS. These markers might extend the therapeutic window during which timely and individualized patient management might be possible.

Cardio-renal syndromes.

'Cardio-Renal syndromes' (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Proline-functionalised calix[4]arene: an anion-triggered hydrogelator.

A water-soluble, chiral calix[4]arene has been found to form hydrogels when triggered by the presence of specific anions, with efficacy linked to the Hofmeister series; the gel properties are modified by the associated cations, and gelation can be reversibly switched off by increasing pH.

Rapid nondestructive on-site screening of methylamphetamine seizures by attenuated total reflection fourier transform infrared spectroscopy.

The identification and quantification of illicit substances in the field is often desirable. Fourier transform infrared spectroscopy (FT-IR) has both qualitative and quantitative capabilities and field portable instruments are commercially available. Transmission infrared spectra of mixtures containing ephedrine hydrochloride, glucose, and caffeine and attenuated total reflection (ATR) infrared spectra of mixtures composed of methylamphetamine hydrochloride, glucose, and caffeine were used to develop principal component regression (PCR) calibration models. The root mean sum of errors of predictions (RMSEP) of all individual components in a mixture from a single measurement was <6% w/w, which reduced to approximately 3% w/w when triplicates were averaged. Sample mixing and grinding are essential to minimize the effect of heterogeneity, as deviations of up to 20% w/w were observed for single measurements of unground samples. Poor predictions of the components in a mixture occurred when samples were "contaminated" with substances not present in the calibration set, as would be expected. When only a single analyte (drug) was targeted, using a calibration set that contained both contaminated and uncontaminated samples, an RMSEP of approximately 4% w/w was achieved. The results demonstrate that ATR-FT-IR has the potential to quantify methylamphetamine samples, and possibly other licit or illicit substances, in at-seizure and on-site scenarios.