Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen—a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders.O objetivo do presente estudo foi investigar a atividade anti-inflamatória in vitro de nanossuspensões e do complexo de inclusão contendo naproxeno. Esse fármaco é derivado de ácido propiônico, com ação analgésica, antipirética e antiinflamatória. A obtenção dessas formulações teve por finalidade o aumento da solubilidade e da atividade anti-inflamatória do fármaco. Os métodos por precipitação em solução aquosa por evaporação e por empastagem foram modificados para a obtenção da nanossuspensão e do complexo de inclusão, respectivamente. Para a avaliação da atividade anti-inflamatória das formulações utilizou-se ensaio in vitro modificado de inibição de tripsina. As propriedades físico-químicas das formulações propostas foram determinadas utilizando espectroscopia UV e de infravermelho, além de estudos de solubilidade. O complexo de inclusão de naproxeno apresentou menor atividade antitripsina, quando comparado ao composto livre e à nanossuspensão. Em conclusão, entre as formulações avaliadas, a nanossuspensão de naproxeno apresentou maior efeito anti-inflamatório. Esse efeito foi devido à redução da dimensão das partículas de naproxeno para a escala nanométrica. Com base nos resultados obtidos, a atividade da nanossuspensão de naproxeno foi notável. Dessa forma, essa formulação apresenta potencial para o tratamento de distúrbios inflamatórios

Anti-Urolithiatic Activity of Melia Azedarach Linn Leaf Extract in Ethylene Glycol-Induced Urolithiasis in Male Albino Rats

Purpose: To investigate the anti-urolithiatic activity of the aqueous and alcoholic extracts of Melia azedarach Linn leaves in calcium oxalate urolithiasis in male albino rats.Methods: The effect of oral administration of aqueous and ethanol extracts of Melia azedarach Linn leaves on calcium oxalate urolithiasis has been investigated. Lithiasis was induced by oral adminstration of ethylene glycol (0.75 %v/v) in male albino rats for 28 days. Each of the extract (250 mg/kg) was administered orally day 0 as a prophylactic regimen and from day 15 as a curative regimen. Regular administration of ethylene glycol caused hyperoxaluria in ethylene glycol-fed animals, leading to increased renal retention and excretion of oxalate, calcium and phosphate. Histopathological study, urine microscopy, serum analysis and biochemical analysis of kidney homogenate were performed.Results: Oxalate and calcium excretion in urine increased (p < 0.01) to 3.68 ± 0.01 and 4.5 ± 0.01 mg/24 h, respectively, in lithiatic control animals compared to (0.37 ± 0.01 and 1.27 ± 0.12 mg/24 h) for the normal control group. Treatment with aqueous or ethanol extract (250 mg/kg, p.o.) significantly (p <0.01) reduced the elevated levels of calcium, oxalate and phosphate excretion in urine to 0.79 ± 0.01 and 1.09 ± 0.04 mg/24 h, respectively. Following treatment with the ethanol extract (250mg/kg), serum creatinine excretion was restored from 0.95 ± 0.01 mg/24 h to the normal level of 0.87 ± 0.01 mg/24 h. The results were comparable to those of the standard drug, allopurinol (50 mg/kg p.o.).Histopathological data for the kidney supported the foregoing results.Conclusions: The results demonstrate that the aqueous and ethanol extracts of Melia azedarach Linn leaves have potent antiurolithiatic activity against ethylene glycol-induced calcium oxalate urolithiasis in male albino rats.Keywords: Melia azedarach, Antiurolithiatic, Ethylene glycol, Urolithiasis, Excretion, Kidne

INVESTIGATION ON ANTIDIARRHOEAL ACTIVITY OF ARISTOLOCHIA INDICA LINN. ROOT EXTRACTS IN MICE

Background: The present study aimed at investigating the effect of ethanolic extract (EtAI), and aqueous extract (AqAI) of Aristolochia indica Linn roots on castor oil-induced diarrhoea and study on small intestinal transit. Phytochemical analysis of extracts was performed as per standard procedure. Materials and Methods: The oral toxicity study using Swiss albino mice was performed in accordance with OECD guidelines. The EtAI and AqAI extracts of Aristolochia indica Linn were studied for antidiarrhoeal property using castor oil-induced diarrhoeal model and charcoal-induced gastrointestinal motility test in Swiss albino mice. Results: Among the tested doses of 200 and 400 mg/kg body weight, the extracts reduced the frequency and severity of diarrhoea in test animals throughout the study period. At the same doses, the extract delayed the intestinal transit of charcoal meal in test animals as compared to the control and the results were statistically significant. Conclusion: Experimental findings showed that ethanol extract of Aristolochia indica Linn root possess significant antidiarrheal activity and may be a potent source of anti-diarrhoeal drug in future

Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020.

BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019.ResultsAll samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5-6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic.ConclusionAlthough blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak

Hemodynamic predictors of aortic dilatation in bicuspid aortic valve by velocity-encoded cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Congenital Bicuspid Aortic Valve (BAV) is a significant risk factor for serious complications including valve dysfunction, aortic dilatation, dissection, and sudden death. Clinical tools for identification and monitoring of BAV patients at high risk for development of aortic dilatation, an early complication, are not available.</p> <p>Methods</p> <p>This paper reports an investigation in 18 pediatric BAV patients and 10 normal controls of links between abnormal blood flow patterns in the ascending aorta and aortic dilatation using velocity-encoded cardiovascular magnetic resonance. Blood flow patterns were quantitatively expressed in the angle between systolic left ventricular outflow and the aortic root channel axis, and also correlated with known biochemical markers of vessel wall disease.</p> <p>Results</p> <p>The data confirm larger ascending aortas in BAV patients than in controls, and show more angled LV outflow in BAV (17.54 ± 0.87 degrees) than controls (10.01 ± 1.29) (p = 0.01). Significant correlation of systolic LV outflow jet angles with dilatation was found at different levels of the aorta in BAV patients STJ: r = 0.386 (N = 18, p = 0.048), AAO: r = 0.536 (N = 18, p = 0.022), and stronger correlation was found with patients and controls combined into one population: SOV: r = 0.405 (N = 28, p = 0.033), STJ: r = 0.562 (N = 28, p = 0.002), and AAO r = 0.645 (N = 28, p < 0.001). Dilatation and the flow jet angle were also found to correlate with plasma levels of matrix metallo-proteinase 2.</p> <p>Conclusions</p> <p>The results of this study provide new insights into the pathophysiological processes underlying aortic dilatation in BAV patients. These results show a possible path towards the development of clinical risk stratification protocols in order to reduce morbidity and mortality for this common congenital heart defect.</p

T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations

Localized double-quantum filtered correlated spectroscopy on 3T MRI/MRS scanner

Standard localized magnetic resonance spectroscopic sequences employ single quantum coherences for excitation and detection. This results in a complex spectra containing large number of resonances. In this thesis we have developed a novel volume localized spectroscopic technique that excites multiple quantum coherences in coupled spin clusters (metabolites) and then reconvert them into single quantum coherences for detection. This results in filtering of uncoupled resonances and also suppresses water with high efficiency. The resulting spectra is reduced in complexity due to the absence of uncoupled resonances.;The technique has been developed in volume localized mode and implemented on a 3T scanner. The technique has been designed to get single-scan coherence pathway selection under gradient-controlled echo filtering, ensuring optimum use of the dynamic range of the receiver electronics.;The multiple quantum preparation sandwich consists of 90° -- t1 -- 90° RF pulse sequence. The period t1 can be optimized for maximizing the desired multiple quantum coherence. The final 90° pulse reconverts the multiple quantum coherences into single quantum coherences. The slice selection gradients are combined with the three RF pulses for volume localization.;The sequence has been tested on phantoms of ethanol and ethyl acetate. The singlets are suppressed as expected. Only the double quantum coherence are able to pass through the double quantum coherence pathway. Preliminary in vivo results for identification of EMCL and IMCL in human calf muscle has been presented

Neonatal onset Cockayne syndrome: A rare photogenodermatosis

Cockayne syndrome (CS) is a rare genodermatosis with autosomal recessive inheritance and around 180 cases have been reported worldwide. It results from mutation in genes ERCC8 and ERCC6 coding for proteins involved in transcription-coupled repair. It is characterized by profound growth retardation, microcephaly, neurodevelopmental impairment, photosensitive skin eruption, premature skin aging, disproportionate large hands, feet and ears, ocular defects, and extensive demyelination. It spans a phenotypic spectrum that includes classic (CS-I), rare severe form with onset from birth (CS-II) and late onset milder form (CS-III). Here, we report an infant with neonatal onset CS-II along with a brief review of the literature