Inhibition of the angiotensin II type 2 receptor AT2R is a novel therapeutic strategy for glioblastoma.

Glioblastoma (GBM) is an aggressive malignant primary brain tumor with limited therapeutic options. We show that the angiotensin II (AngII) type 2 receptor (AT2R) is a therapeutic target for GBM and that AngII, endogenously produced in GBM cells, promotes proliferation through AT2R. We repurposed EMA401, an AT2R antagonist originally developed as a peripherally restricted analgesic, for GBM and showed that it inhibits the proliferation of AT2R-expressing GBM spheroids and blocks their invasiveness and angiogenic capacity. The crystal structure of AT2R bound to EMA401 was determined and revealed the receptor to be in an active-like conformation with helix-VIII blocking G-protein or ß-arrestin recruitment. The architecture and interactions of EMA401 in AT2R differ drastically from complexes of AT2R with other relevant compounds. To enhance central nervous system (CNS) penetration of EMA401, we exploited the crystal structure to design an angiopep-2-tethered EMA401 derivative, A3E. A3E exhibited enhanced CNS penetration, leading to reduced tumor volume, inhibition of proliferation, and increased levels of apoptosis in an orthotopic xenograft model of GBM.

Challenges in direct determination of Glyphosate and aminomethylphosphonic acid in water by liquid chromatography-tandem mass spectrometry at modified reverse phase columns: Effect of matrix interferences in fresh and hard water systems.

This study validated two underivatized methods (M1 and M2) according to the Eurachem guidelines to analyze the herbicide Glyphosate and its major metabolite aminomethylphosphonic acid simultaneously by liquid chromatography-tandem mass spectrometry in both fresh and hard waters. Samples were analyzed directly after filtration through 0.22 µm syringe filters in M1, while samples were acidified with acetic acid before filtration in M2. Spike recoveries were greater than 80% for Glyphosate and aminomethylphosphonic acid in both methods. The limit of quantitation was 0.5 µg/L for M1, and 0.1 µg/L for M2 by using matrix-matched calibrations. The linear regression coefficient of both methods was greater than 0.995. The expanded uncertainty was found to be less than 25% for both. Moreover, M1 has an additional mass spectral confirmation ability, and the column and the mobile phase used in M2 can be used to analyze the inert surfactant used in Glyphosate formulations, Polyethoxylated tallow amine. The accuracy of the developed methods was assured by participating in a proficiency testing program against M2 and conducting the t-test for results generated by both M1 and M2. Both methods, therefore, can be used to determine Glyphosate and aminomethylphosphonic acid content concurrently in fresh and hard waters.

Aqueous Humour Ofloxacin Concentration after Topical Instillation in Patients with Dry Eye Disease.

Background and Objectives: A prospective, randomized clinical trial was conducted to evaluate the concentration of ofloxacin in the aqueous humour (AqH) of patients suffering from dry eye disease (DED) after topical instillation. Materials and Methods: Ninety-one (91) cataract patients scheduled for phacoemulsification were categorized into three groups according to DED severity. Group I (n = 17) was comprised of subjects without DED, patients in group II (n = 37) were evaluated as having non-severe DED, while group III (n = 37) consisted of patients suffering from severe DED. Preoperatively, patients received 4 drops of 0.3% of ofloxacin at 15 min intervals. One hour after the last instillation, aqueous samples were collected intraoperatively. Results: The median AqH concentration of ofloxacin in group I was 199.9 ng/mL (range 92.2−442.8 ng/mL), while in group II it was 530.5 ng/mL (range 283.7−1004.9 ng/mL), and 719.2 ng/mL (range 358.0−1512.4 ng/mL) in Group III, p < 0.001 (Kruskal-Wallis tests). Pairwise tests (two-tailed with Bonferroni corrections) between groups resulted in a p-value of 0.001 when group II was compared to group I and group III was compared to group I, and a p-value of 0.020 when group II was compared to group III. The severity of DED, across groups I, II, and III, and the levels of ofloxacin revealed a strong positive correlation (r = 0.639, p < 0.001). Conclusions: Ofloxacin concentration in the AqH after topical drop instillation may be affected by the degree of ocular surface inflammation in patients suffering from DED.

In vivo quantification and pharmacokinetic studies of cotinine in mice after smoke exposure by LC-MS/MS.

A sensitive analytical method was developed and validated for the quantification of cotinine in mouse plasma after exposure to smoke of 0.5, 1.0, and 1.5 commercially available cigarettes, using liquid chromatography tandem mass spectrometry. The method was validated over a linear concentration range of 0.075-20.0 ng/mL with the R2 value being higher than 0.99. Both the precision (coefficient of variation; %) and accuracy (relative error; %) were within acceptable criteria of <15%. The lower limit of quantification (LLOQ) for cotinine was 0.075 ng/mL with sufficient specificity, accuracy, and precision. Following exposure to 0.5, 1.0, and 1.5 cigarette smoke, it was observed that the AUC and the Cmax increased linearly as the doses increased. The pharmacokinetics of cotinine was found linear for the range of 0.5-1.5 commercial cigarette smoke. The quantification of the concentration of cotinine in mouse plasma after smoke exposure will facilitate future behavioral and toxicological experiments in animals and may prove useful in predicting cotinine levels in humans during smoking.

Development and validation of analytical methodologies for the quantification of PCK3145 and PEG-PCK3145 in mice.

PCK3145 is an anti-metastatic synthetic peptide against prostate cancer. The objective of the study is to develop and validate novel and sensitive methods for the determination of PCK3145 and Pegylated PCK3145 in mouse plasma. An LC-MS/MS method was developed and validated for the determination of PCK3145 giving high sensitivity and linearity in the range of 0.125-4.0 µg/mL. PCK3145 characterised by short half-life, therefore, it was conjugated with the poly ethylene glycol (PEG). However, LC-MS/MS has been more difficult to apply for the quantitative analysis of PEGylated peptides due to the large size. A UHPLC-UV method was developed and validated for the determination of PEG-PCK3145, with linearity of 0.05-2.0 mg/mL. In order to further improve the sensitivity for the detection of PEG-PCK3145, an indirect ELISA method was used. It was found that this method was capable of detecting PCK3145 through the quantification of PEG with excellent sensitivity found at 0.132 ng/mL. The in vitro proteolytic stability of PCK3145 and PEG-PCK3145 in mouse plasma and whole blood was studied by LC-MS/MS and UHPLC, respectively. The LC-MS/MS and ELISA methods can be applied for monitoring levels of PCK3145 in mouse plasma for in vivo pharmacokinetic and bioavailability animal studies.

Nano-Antenna Coupled Infrared Detector Design.

Since the 1940s, infrared (IR) detection and imaging at wavelengths in the two atmospheric windows of 3 to 5 and 8 to 14 µm has been extensively researched. Through several generations, these detectors have undergone considerable developments and have found use in various applications in different fields including military, space science, medicine and engineering. For the most recently proposed generation, these detectors are required to achieve high-speed detection with spectral and polarization selectivity while operating at room temperature. Antenna coupled IR detectors appear to be the most promising candidate to achieve these requirements and has received substantial attention from research in recent years. This paper sets out to present a review of the antenna coupled IR detector family, to explore the main concepts behind the detectors as well as outline their critical and challenging design considerations. In this context, the design of both elements, the antenna and the sensor, will be presented individually followed by the challenging techniques in the impedance matching between both elements. Some hands-on fabrication techniques will then be explored. Finally, a discussion on the coupled IR detector is presented with the aim of providing some useful insights into promising future work.

Development and validation of a UHPLC-UV method for the determination of a prostate secretory protein 94-derived synthetic peptide (PCK3145) in human plasma and assessment of its stability in human plasma.

PCK3145 is a synthetic peptide, derived from the Prostate Secreted Protein 94 (PSP94), with promising in vitro and animal in vivo results in prostate cancer. The aim of the present study was to develop and validate a fast and robust ultra-high-performance liquid chromatography with ultraviolet detection for the determination of PCK3145 in human plasma which would be suitable for the assessment of PCK3145 stability to proteolytic degradation. Following protein precipitation, chromatographic separation was carried out on an Aeris Peptide C18 column with mobile phase consisting of acetonitrile-water at a flow-rate of 0.50 mL/min. The calibration curve was linear over the range 0.50-20.00 µg/mL. Intra- and inter-day percentage relative standard deviation and relative error were ≤10%. The limit of detection and the lower limit of quantification were 0.15 and 0.50 µg/mL, respectively. Recovery of PCK3145 from human plasma was ≥96%. The peptide presented high stability in whole blood and in human plasma (>98% intact peptide after 24 h incubation at 37°C in human plasma), which represents a distinctive advantage in the therapeutic use of the compound. This is the first validated UHPLC method for the determination of PCK3145 reported, and it was successfully applied in the study of the proteolytic stability of PCK3145 in human plasma ex vivo. Copyright © 2016 John Wiley & Sons, Ltd.

Super-Selective Trans-Catheter Arterial Embolization (TAE) of the Vesical Arteries in the Management of Intractable Hematuria Secondary to Advanced Bladder and Prostate Cancers.

This article was previously presented as an abstract at the 18th UAA Congress, Seoul, October 15-17, 2020, and the abstract was published in The International Journal of Urology. It was also presented as an e-poster at the 2021 BAUS Annual Meeting on June 22, 2021. Introduction In frail patients intractable hematuria secondary to advanced pelvic malignancies is a clinical challenge. Super-selective TAE of the vesical arteries is a suitable minimally invasive option. We present our experience in this patient cohort. Patients and methods All patients who underwent TAE from January 2014 to December 2019 were included. Super-selective TAE of the superior and inferior vesical arteries was done using 300-500µ polyvinyl alcohol (PVA) particles. Demographic data, cancer stage, associated urinary system obstruction, pre-embolization palliative treatment, chemotherapy, and radiotherapy were recorded. Technical and clinical success, time to cessation of hematuria, recurrence of hematuria, and complications were recorded. Data are presented as mean ± standard deviation, and statistical significance is set at p<0.05. Results From 2014 to 2019, seven patients underwent eight procedures. The average patient's age was 60.6±10.3 years. All presented with gross hematuria, six due to locally advanced and/or metastatic bladder cancer, and one due to prostate cancer. The average time of hematuria clearance was 60 hours. The average hemoglobin levels at the time of the procedure, one month, and six months post-embolization were 9.6±1.7 g/dL, 10.6±1.5 g/dL (p<0.05), and 9.6±0.9 g/dL, respectively (p>0.05). Packed red blood cell (PRBC) requirements decreased from 7±2 units to 5±3 units after the procedure (p >0.05). The patients were followed up for an average of 13.6 months and four had a recurrence at an average of four months post-embolization. Conclusion Super-selective TAE is an effective palliative method in controlling intractable hematuria. The risks of major surgery and anesthesia are omitted, and the procedure can be repeated as needed. Furthermore, post-embolization complications, using this technique, are minor and manageable.

Perception of urinary biomarker tests among patients referred with suspected urological malignancy.

Objective: To determine the acceptability of a non-invasive urinary biomarker test in place of conventional flexible cystoscopy for the diagnosis of bladder cancer in patients referred to a Rapid Access Haematuria Clinic (RAHC) with suspected urological malignancy. Patients and methods: Patients attending a RAHC were recruited to a prospective observational study evaluating a novel urinary biomarker (URO17™) for the detection of bladder cancer and invited to complete a two-part structured questionnaire. Questions related to demographics, attitudes towards conventional cystoscopy and the minimal acceptable sensitivity (MAS) at which a urinary biomarker would be considered an alternative to flexible cystoscopy both before and after undergoing the procedure. Results: A total of 250 patients completed the survey; the majority of whom were referred with visible haematuria (75.2%). One hundred seventy-one (68.4%) would be willing to accept a urinary biomarker in place of cystoscopy, with 59 (23.6%) expressing preference for the biomarker with a MAS as low as 85%. Conversely, 74 patients (29.6%) would not be willing to accept a urinary biomarker, regardless of its sensitivity. A significant number of patients reported a change in MAS after undergoing cystoscopy, with 80 (32.0%) and 16 (6.4%) increasing and decreasing the required value respectively (P = 0.001). The greatest increase was seen in the proportion of patients unwilling to accept a urinary biomarker regardless of its sensitivity, rising from 29.6% to 38.4%. Conclusions: Although many patients attending a RAHC would be willing to accept a urinary biomarker test in place of conventional flexible cystoscopy for the detection of bladder cancer, effective patient, public and clinician engagement will be necessary at all stages of implementation if it is to become an established component of the diagnostic pathway.

High-grade vesicoureteral reflux in infants: Our experience with endoscopic subureteric injections.

BACKGROUND: Vesicoureteral reflux (VUR) is the most common urological anomaly in pediatric patients. Management options for VUR vary from continuous antibiotic prophylaxis (CAP) to surgery via either endoscopic subureteric injection of a bulking agent or open anti-reflux surgery. In this study, we assess the efficacy of subureteric injections of Dextranomer/Hyaluronic acid Copolymer (Deflux) in managing primary VUR in infant patients with high-grade VUR. METHODS: From 2010 to 2015, children less than 1-year-old with primary high-grade VUR were observed prospectively following the administration of endoscopic subureteric injections of Dextranomer/Hyaluronic Acid Copolymer (Deflux). The diagnosis of VUR was based on MCUG, and all patients underwent a holistic clinical, laboratory, and radiological assessment before and after the intervention. Complete success was defined as the resolution of VUR on follow up 1 year post-operatively. RESULTS: A total of 30 infants (50 renal units) with high-grade VUR (grades IV and V) were included in the study. The mean age at surgery was 6.3 ± 2.5 months. Most of the patients presented with a urinary tract infection (90%). Complete symptomatic relief was achieved in 27 patients (90%) at the first post-operative follow-up. Forty-four renal units received one injection, while six required a second injection as they did not meet our treatment success criteria. No patients required a third injection or referral for open surgery. CONCLUSION: Endoscopic injection of Dextranomer/Hyaluronic acid Copolymer (Deflux) at the vesicoureteral junction is an effective minimally invasive intervention to treat high grades VUR (IV-V) infants.

Evaluation of transverse dorsal lumbotomy in management of PUJ obstruction in patients younger than 6 months.

OBJECTIVE: The transverse dorsal lumbotomy approach provides excellent exposure to the PUJ and causes minimal tissue damage. In this study, we assess the efficacy of dorsal lumbotomy in PUJ obstruction in children younger than 6 months. METHODS: All children less than 6 months who were managed with the dorsal lumbotomy approach between 2009 and 2017 were reviewed prospectively. Data included: demographic data, pre/post-operative renal ultrasound scan with SFU grading and RDS, operative time, post-operative complications, and follow up results. RESULTS: A total of 42 children with a mean age of 4.4 ± 1 months were included. On pre-operative RDS, all patients had an obstructive pattern and a SRF of 30.3 ± 9.3. The mean operative duration was 49 min and analgesia was minimal. Post-operative ultrasound at 6 months showed an improvement in hydronephrosis (p < 0.05) and a mean SRF of 39.3 ± 6.1 (p < 0.001). CONCLUSION: Transverse dorsal lumbotomy approach is a safe and efficient alternative in patients less than 6 month.

Renal Carcinoma Patterns and Prevalence in Bahrain: A Descriptive Study.

Cancer is a major health problem with a significant impact on society and healthcare systems. In 2018, approximately 18.1 million cases of cancer were diagnosed and 9.6 million deaths were documented. Urological cancers account for 12.9% of new cases recorded and 8% of deaths due to cancer worldwide. The latest cancer registries covering the Gulf Cooperation Council (GCC) countries report that 4078 cases of renal cell carcinoma were diagnosed from 1998 to 2012. Urological cancers comprised 9.4% of all cases with an incidence rate of 16.1% in males and 3.2% in females. All renal cancer cases documented in Salmaniya Medical Complex (SMC) from 2014 to 2018 were reviewed. Data collected for all patients from the electronic health record system included age at diagnosis, gender, laterality of cancer (where applicable), histological type, and TNM (tumor, node, metastasis) classification and staging. Furthermore, World Health Organization (WHO) grade and data were collected for kidney cancer cases. Statistical analysis was carried out using Statistical Package for the Social Sciences (SPSS) version 23 (IBM Corp, Armonk, NY). From 2014 to 2018, there were 65 documented cases of kidney cancer with an average caseload of 13 cases per year. The mean age at diagnosis was 57.6 years. Clear cell carcinoma was the most common histological subtype (37.5%). Stage 1 was the most common stage at diagnosis (35.4%) and the age-standardized mortality rate for males and females were 4.59 and 4.58 in 100,000, respectively. Kidney cancer is a urological malignancy that can pose a burden on both the patient and the healthcare system. There should be a national effort to better understand the etiology and epidemiology of this disease entity with regard to our population. Such efforts would make data regarding diagnosis, management, and follow-up more accessible and would add positively to our healthcare system.

Ultrasound heterogeneity as an indicator of testicular salvage in testicular torsion: A single center experience.

OBJECTIVE: Testicular torsion is a common urological emergency, mainly in the younger population. Our aim is to evaluate the efficacy and value of testicular echogenicity in predicting testicular viability. METHODS: Patients who were older than 13 years of age and were discharged with the diagnosis of testicular torsion were reviewed. Data obtained included demographic data, history, physical examination results, ultrasound findings including size, color Doppler flow, and echotexture, torsion degrees, and surgical procedure. In addition, the histopathological findings of patients who underwent orchiectomy were reviewed. RESULTS: A total of 71 cases were diagnosed with testicular torsion between January 2016 to December 2018. The mean age at presentation was 20.4±7.0 years. The average time from the onset of pain until the presentation was 36.0±55.1 h. Out of the 71 ultrasound scans reviewed, 45.1% showed homogenous echotexture and 54.9% showed heterogeneous echotexture of the affected testis. On scrotal exploration, the mean degree of torsion was 475.7±301.8 degrees; 66.2% of the patients had a viable testis; and bilateral orchidopexy was done. The remaining 33.8% had a non-viable testis. Homogenous echotexture was after an average of 13.5 h of scrotal pain, while heterogeneous echotexture presented after 53.7 h of scrotal pain. There was a statistically significant difference between the time of presentation and echotexture changes on scrotal ultrasonography (p<0.01). The relationship between echotexture changes and testicular viability was statistically significant as well (p<0.001). CONCLUSION: A long time since the onset of pain coupled with heterogeneous changes in testicular parenchyma is a good indicator of non-viability. However, we still advocate for surgical exploration as the gold standard in diagnosis and management.

Transurethral Catheterization in Early Training: The Impact of Peer-Led Mentorship.

INTRODUCTION: Transurethral catheterization (TUC) is a common hospital procedure. According to the literature, junior doctors contribute to the majority of TUC-related injuries. Our aim is to evaluate the immediate and long-term impact of a short procedure-centric TUC workshop on junior doctor's confidence, procedural knowledge, and ability to identify potential complications of catheterization. MATERIALS AND METHODS: Intern doctors were invited to attend a one-hour workshop on TUC. A questionnaire was completed before and after the workshop. Three months later, the questionnaire was readministered to assess the workshop's long-term impact. The questionnaire consisted of three domains. A: experience, training, and confidence levels (using 5-point Likert scales), B: procedural knowledge (the highest possible score was 10 points), and C: identification of TUC-related complications (the highest possible score was 3 points). RESULTS: 81 interns participated and reported a confidence level of 3.03 ± 1.05 in performing a straightforward TUC. Preworkshop domain B and domain C were 3.92 ± 1.63 and 1.75 ± 0.69 points, respectively. After the workshop, reported confidence levels improved to 3.71 + 1.02 (p < 0.05). Likewise, the scores in domains B and C increased significantly to 8.85 ± 1.40 (p < 0.005) and 2.65 ± 0.6 (p < 0.005), respectively. Three months later, the same parameters were evaluated, and confidence levels were higher than those of the preworkshop levels at 3.83 ± 0.77 (p < 0.05). The average domain B score was 7.85 ± 1.88 (p < 0.005), and domain C score was 2.69 ± 0.53 (p < 0.005). All scores reported after three months were significantly better than the preworkshop levels (p < 0.005), but there were no statistically significant differences when compared to the immediate postworkshop scores (p > 0.05). CONCLUSION: Short peer-led TUC workshops positively impact intern doctors' confidence levels, procedural knowledge, and identifying complications.

Rare association of Klippel-Feil syndrome with situs inversus totalis and review of the genetic background.

Klippel-Feil syndrome (KFS) is a rare congenital anomaly in forming the cervical vertebrae resulting in the fusion of two or more of the vertebrae. KFS is associated with many congenital anomalies, some of which are common and well known. Here, we report a child with an extremely rare association of KFS with situs inversus totalis (SIT). Both KFS and SIT are genetically heterogeneous and their co-occurrence suggests a high possibility of sharing the same underlying causative agent. Here, we review the genetic background that is known for these two conditions in the literature.

Genome-wide association analysis of chickpea germplasms differing for salinity tolerance based on DArTseq markers.

Soil salinity is significant abiotic stress that severely limits global crop production. Chickpea (Cicer arietinum L.) is an important grain legume that plays a substantial role in nutritional food security, especially in the developing world. This study used a chickpea population collected from the International Center for Agricultural Research in the Dry Area (ICARDA) genebank using the focused identification of germplasm strategy. The germplasm included 186 genotypes with broad Asian and African origins and genotyped with 1856 DArTseq markers. We conducted phenotyping for salinity in the field (Arish, Sinai, Egypt) and greenhouse hydroponic experiments at 100 mM NaCl concentration. Based on the performance in both hydroponic and field experiments, we identified seven genotypes from Azerbaijan and Pakistan (IGs: 70782, 70430, 70764, 117703, 6057, 8447, and 70249) as potential sources for high salinity tolerance. Multi-trait genome-wide association analysis (mtGWAS) detected one locus on chromosome Ca4 at 10618070 bp associated with salinity tolerance under hydroponic and field conditions. In addition, we located another locus specific to the hydroponic system on chromosome Ca2 at 30537619 bp. Gene annotation analysis revealed the location of rs5825813 within the Embryogenesis-associated protein (EMB8-like), while the location of rs5825939 is within the Ribosomal Protein Large P0 (RPLP0). Utilizing such markers in practical breeding programs can effectively improve the adaptability of current chickpea cultivars in saline soil. Moreover, researchers can use our markers to facilitate the incorporation of new genes into commercial cultivars.

Fibroepithelial Polyp in a Child: A Rare Pathology of Upper Urinary Tract Obstruction.

Fibroepithelial polyp is a rare benign tumor of the urothelial system that originates from the mesoderm. Polyps are usually small and located in the upper urinary tract and ureteropelvic junction. However, in the pediatric population, such polyps are more common in the posterior urethra and will present with symptoms of urinary tract obstruction. Some will present with flank pain and hematuria, resembling symptoms of ureteric stones. In this case, we discuss a nine-year-old boy presenting with complaints of flank pain and hematuria for one year. Following laboratory and radiological investigations, the left ureter was dilated at the mid-lumbar region with an anteroposterior diameter of 2.3 x 0.6 cm and a left renal pelvis anteroposterior diameter of 2.2 cm. An ultrasound scan identified an intraluminal lesion suspected to be a fibroepithelial polyp. Management was carried out via retroperitoneal surgery with upper ureteral resection and end-to-end anastomosis. Postoperatively, the patient's symptoms improved, and a subsequent ultrasound scan and renal function test showed improvement of the left hydroureter and hydronephrosis.

Laparoscopic cholecystectomy in children with sickle cell disease: A simple modified technique.

INTRODUCTION: Sickle cell disease and other hemoglobinopathies are prevalent in Bahrain. In our hospital, we often encounter children with gallstones; sometimes gallstones are discovered on routine abdominal ultrasound, and in other cases, patients present with symptoms. Elective cholecystectomy has been controversial in patients with sickle cell disease and cholelithiasis because surgery can be a challenge. Therefore, the aim of this study was to assess the safety of elective cholecystectomy in children with sickle cell disease with cholelithiasis, as well as the safety and efficacy of a simple modification to the conventional laparoscopic cholecystectomy technique using two natural creases in the skin. METHODS: The modified technique employs four ports, two of which were placed in natural crease lines, specifically the umbilicus and the groin crease. The procedure was elective for patients with sickle cell disease with gallstones. All patients received either a preoperative blood transfusion or an exchange transfusion to reduce the risk of postoperative sickle cell complications. RESULTS: Eighty-one patients with sickle cell disease with gallstones underwent our simple modified laparoscopic cholecystectomy procedure. The mean ± SD operative time was 58.43 ± 8.02 minutes (range, 45-80 minutes). Only eight patients (9.9%) experienced postoperative complications; six had fever, and two had a sickle cell crisis. None of the patients required conversion to open cholecystectomy or intensive care management. CONCLUSION: Our simple modified laparoscopic cholecystectomy using two skin creases is a safe and feasible elective procedure in children with sickle cell disease that provides excellent cosmesis.

Effects of Exposure to Tobacco Cigarette, Electronic Cigarette and Heated Tobacco Product on Adipocyte Survival and Differentiation In Vitro.

Cigarette smoking (CS) causes significant morbidity worldwide, attributed to the numerous toxicants generated by tobacco combustion. Electronic cigarettes (ECIG) and heated tobacco products (HTP) are considered alternative smoking/vaping products that deliver nicotine through an inhaled aerosol and emit fewer harmful constituents than CS. However, their long-term impacts on human health are not well established. Nicotine exposure has been linked to lipolysis and body weight loss, while smoking has been associated with insulin resistance and hyperinsulinemia. Enhanced function of beige (thermogenic) adipocytes has been proposed as a means to reduce obesity and metabolic disorders. In this study, we compared the effect of extract-enriched media via exposure of culture medium to CS, HTP aerosol, and ECIG aerosol on the viability and the differentiation of 3T3-L1 pre-adipocytes to beige adipocytes. Only CS extract caused a decrease in cell viability in a dose- and time-dependent manner. Furthermore, relative lipid accumulation and expression levels of the adipocyte markers Pgc-1α, Ppar-γ and Resistin were significantly decreased in cells exposed to CS extract. Our results demonstrate that CS extract, in contrast to HTP and ECIG extracts, significantly impairs differentiation of pre-adipocytes to beige adipocytes and may therefore impact significantly adipose tissue metabolic function.

The Effect of Low-Doses of Caffeine and Taurine on Convulsive Seizure Parameters in Rats.

INTRODUCTION: Caffeine, an adenosine-receptor blocker, is believed to have neuronal excitatory effects, while Taurine, a mammalian amino acid, was shown to have neuroinhibitory effects. Aim: The aim of this study was to investigate the effects of acute and chronic administration of low doses of Caffeine and Taurine on the seizure threshold in rats. Methods: Six-week-old Sprague-Dawley male rats (n = 280) were divided randomly into five groups (control, acute caffeine intake, acute taurine intake, chronic caffeine intake and chronic taurine intake), with five subgroups per group according to five different doses of Pentylenetetrazole (PTZ) injections. Each subgroup consisted of eight rats. Data was entered and analyzed using Microsoft EXCEL and AddinsoftTM XLSTAT (Version 2012.6.06; New York, NY, USA). p-value = 0.05 was regarded as statistically significant. Results: There was a significant decrease in the latency of PTZ-induced seizures with both acute (p-value < 0.05) and chronic (p-value < 0.01) Caffeine treatment groups. Chronic exposure to Caffeine exhibited an increase in the probability of seizures (p-value < 0.05). However, acute exposure to Caffeine did not show a significant impact on the probability of seizures. Neither acute nor chronic exposures to Taurine had an effect on the probability of seizures, nor on the latency of PTZ-induced seizures. Discussion: Our study found that acute as well as chronic exposure to low doses of Caffeine (50 and 80 mg/kg) reduces the threshold, and hence increases the likelihood for seizures since it favors a state of neuronal hyper excitability through blocking of all adenosine receptors. On the other hand, acute or chronic exposure to Taurine did not show a significant effect on the PTZ-induced seizures parameters.