Diagnostic significance of miR‐21, miR‐141, miR‐18a and miR‐221 as novel biomarkers in prostate cancer among Egyptian patients

Prostate cancer (PC) is considered as the fifth cause of cancer deaths worldwide. The exact etiopathogenesis is unclear; however, genetic predisposition, hormonal influencers, lifestyle and environmental factors act as major contributors. It has been found that several miRNAs may play a crucial role in cancer initiation and progression. Here, in this study, we evaluated the peripheral blood levels of miR‐21, miR‐141, miR‐221 and miR‐18a expression among 80 prostate cancer patients (50 localised and 30 metastatic) and 30 benign prostatic hyperplasia patients compared to 50 normal control subjects, using RT‐PCR. Our results of analysis of miR‐21, miR‐141, miR‐18a and miR‐221 in the plasma of PC patients showed that miR‐18a is a powerful discriminator of PC patients from healthy controls as it had the highest AUC (0.966; 95% CI, 0.937–1.000), while miR‐221 provided better differentiation of metastatic from localised PC (sensitivity was 92.9% at 100% specificity), and when we combine miR‐18a and miR‐221 for differentiating patients with MPC, it will increase the sensitivity to 96.4% at a specificity of 100% (AUC, 0.997; 95% CI, 0.988–1.0) (p < .000). This current study recommends that analysis of these miRNAs might have clinical value in enhancing PSA testing.     

Multi-detector computed tomography imaging of blunt chest trauma

Background and purpose

Chest trauma is a significant cause of mortality and morbidity, especially in the younger population. The purpose of this study was to evaluate the role of multi-detector computed tomography (MDCT) in the assessment of patients with blunt chest trauma.

Patients and methods

A prospective study was conducted on thirty (30) patients with blunt chest trauma (21 males and 9 females, aged from 6 to 62 years) and 29 control patients presented with any trauma other than blunt chest trauma (23 males and 6 females, aged from 10 to 68 years) at the Emergency Department, Tanta University Hospital, from January 2013 to February 2014. Cases were subjected to clinical evaluation and radiological assessment of the chest using conventional chest X-ray (CXR) and multi-detector computed tomography.

Results

The most common mode of injury was motor vehicle accidents (56.7%). On MDCT scan, the frequency of chest injuries were; chest wall injuries (86.7%), pleural injuries (80%), parenchymal injuries (56.7%), mediastinal injuries (30%) and finally the dorsal spine injuries (16.7%). MDCT is more sensitive, specific, and accurate than CXR in the assessment of blunt chest trauma and management of patients.

Conclusion

MDCT is the modality of choice for rapid assessment of emergency chest trauma patients, when chest X-ray was inconclusive.     

Molecular Epidemiology of SARS-CoV-2 in Tunisia (North Africa) through Several Successive Waves of COVID-19

Documenting the circulation dynamics of SARS-CoV-2 variants in different regions of the world is crucial for monitoring virus transmission worldwide and contributing to global efforts towards combating the pandemic. Tunisia has experienced several waves of COVID-19 with a significant number of infections and deaths. The present study provides genetic information on the different lineages of SARS-CoV-2 that circulated in Tunisia over 17 months. Lineages were assigned for 1359 samples using whole-genome sequencing, partial S gene sequencing and variant-specific real-time RT-PCR tests. Forty-eight different lineages of SARS-CoV-2 were identified, including variants of concern (VOCs), variants of interest (VOIs) and variants under monitoring (VUMs), particularly Alpha, Beta, Delta, A.27, Zeta and Eta. The first wave, limited to imported and import-related cases, was characterized by a small number of positive samples and lineages. During the second wave, a large number of lineages were detected; the third wave was marked by the predominance of the Alpha VOC, and the fourth wave was characterized by the predominance of the Delta VOC. This study adds new genomic data to the global context of COVID-19, particularly from the North African region, and highlights the importance of the timely molecular characterization of circulating strains.     

Therapy of Hypertension in African Americans

Hypertension in African Americans is a major clinical and public health problem because of the high prevalence and premature onset of elevated blood pressure (BP) as well as the high burden of co-morbid factors that lead to pharmacological treatment resistance (obesity, diabetes mellitus, depressed glomerular filtration rate, and albuminuria). BP control rates are lower in African Americans, especially men, than in other major race/ethnicity-sex groups; overall control rates are 29.9% for non-Hispanic Black men. Optimal antihypertensive treatment requires a comprehensive approach that encompasses multifactorial lifestyle modifications (weight loss, salt and alcohol restriction, and increased physical activity) plus drug therapy. The most important initial step in the evaluation of patients with elevated BP is to appropriately risk stratify them to allow determination of whether they are truly hypertensive and also to determine their goal BP levels. The overwhelming majority of African American hypertensive patients will require combination antihypertensive drug therapy to maintain BP consistently below target levels. The emphasis is now appropriately on utilizing the most effective drug combinations for the control of BP and protection of target-organs in this high-risk population. When BP is > 15/10 mmHg above goal levels, combination drug therapy is recommended. The preferred combination is a calcium antagonist/angiotensin-converting enzyme inhibitor or, alternatively, in edematous and/or volume overload states, a thiazide diuretic/angiotensin-converting inhibitor.     

Complete heart block in a patient with acute lymphoblastic leukaemia: teicoplanin as a possible cause and review of literature

What is known and Objective:  Teicoplanin is a glycopeptide antibiotic used against documented or presumed methicillin‐resistant infections. We report a 31‐month‐old boy with acute lymphocytic leukaemia who developed permanent complete atrioventricular block (CAVB) necessitating pacemaker insertion after receiving teicoplanin for Staphylococcus epidermidis bacteremia. Case summary:  Clinical assessment of the child revealed febrile neutropenia. After thorough assessment and work‐up, the patient was started on teicoplanin intravenously after which he had sudden onset of bradycardia. Electrocardiography showed CAVB that eventually required permanent pacemaker insertion. Twenty‐nine months from the incident, the patient is doing well. What is new and Conclusion:  We report on a case of teicoplanin‐associated CAVB in a child with acute lymphoblastic leukaemia (ALL). This is one of only two similar cases reported in the literature. Teicoplanin remains the most probable cause. The use of teicoplanin should be approached cautiously in the setting of immunosuppression. Whether VZV contributed and teicoplanin triggered remains speculative. Physicians should be aware of this possible complication.     

Live/Real Time Three‐Dimensional Transthoracic Echocardiography in the Evaluation of Post Traumatic Acquired Thoracic Aortic Coarctation

We report a young patient with post traumatic acquired thoracic aortic coarctation in whom three‐dimensional transthoracic echocardiography (3DTTE) demonstrated incremental value over two‐dimensional transthoracic echocardiography (2DTTE). 3DTTE showed (1) en face views of the obstruction site that showed a markedly narrowed, roughly circular orifice measuring 0.33 cm² in area, (2) echogenic tissue encroaching on the graft lumen consistent with fibrosis/thrombus, and (3) no graft protrusion into the aortic lumen, only hypermobility of the medial portion of the graft. These important findings were not detected by 2DTTE. (Echocardiography 2010;27:470‐472)     

Relative bioavailability of griseofulvin lyophilized dry emulsion tablet vs. immediate release tablet: A single-dose, randomized, open-label, six-period, crossover study in healthy adult volunteers in the fasted and fed states

The oral bioavailability of griseofulvin (GF) formulated as a fast disintegrating lyophilized dry emulsion (LDE) tablet was studied and compared to the commercially available immediate release (IR) tablet, as a reference, in both the fasted and fed states in nine healthy volunteers after a single oral dose (125mg) in a crossover design. Furthermore the LDE tablets were ingested with and without water under both the fasted and fed states. In the fasted state, the rate of absorption was found to be significantly faster from LDE tablets, in the presence and absence of water, as shown by a higher C(max) (more than two times higher, p=0.0001) and a shorter t(max) (by more than 3h, p=0.0001) compared to IR tablets. The extent of absorption, expressed as AUC, from LDE tablets in the presence and absence of water was 65% and 77% larger and statistically significantly different relative to the mean AUC from IR tablets (p=0.006). In the fed state, C(max) from LDE tablets ingested with and without water was found to be about 30% and 50% higher, respectively, than the immediate release tablets. A shorter t(max) was also shown whether LDE tablets were ingested with or without water in the fed state as compared to immediate release tablets. The mean AUC from LDE tablets under fed conditions in the presence of water was about 21% larger and was not statistically significantly different from AUC from immediate release tablets (p=0.517). When ingested without water, AUC from LDE tablets was about 43% larger and statistically significantly different relative to AUC from IR tablets (p=0.033). The mean AUC from the LDE tablet ingested with water under fed conditions relative to AUC from LDE tablet ingested without water was not statistically significantly different (p=0.454). Results show that the food effect of the high fat meal is very pronounced in case of the immediate release tablets, Fulvin, than in case of LDE tablets whether given with or without water.     

Incubation in tissue culture media allows isolated rabbit proximal tubules to regain in-vivo-like transport function: response of HCO3 – absorption to norepinephrine

Using a new stop-flow perfusion technique with microspectrofluorometric determination of luminal fluid pH, we have studied which substrates or incubation conditions allow isolated rabbit proximal tubules to attain in-vivo-like rates of HCO3- absorption (J(HCO3)) and maximal responses of J(HCO3) to norepinephrine (NE). Essentially three incubation media were tested: plasma-like HCO(3-)-Ringer solution containing 5 mmol/l D-glucose (G-Ringer sol.), the same solution also containing 10 mmol/l lactate and 5 mmol/l L-alanine, (LAG-Ringer sol.), and two tissue culture media (DMEM and RPMI 1640). Compared to G-Ringer sol., application of LAG-Ringer sol. in the bath and/or lumen, or application of DMEM or RPMI 1640 in the bath either slightly increased or decreased J(HCO3) with borderline significance. However, RPMI 1640 plus 1 mmol/l pyruvate stimulated J(HCO3) by 55%. While NE (10(-5) mol/l), if applied in G-Ringer sol., had no effect, in the presence of LAG-Ringer sol. it increased J(HCO3) by approximately =40%, and in the presence of DMEM or RPMI 1640 it increased J(HCO3) by approximately =100%. This stimulation by NE followed Michaelis-Menten kinetics with an EC50 value of 0.25 micromol/l and was probably mediated by alpha1-adrenergic receptors. Additional cell pH measurements suggest that NE stimulates the basolateral Na+-HCO3- cotransporter which then becomes susceptible to inhibition by cAMP. We conclude that incubation in tissue culture media allows isolated proximal tubules to maintain a better functional state than the commonly used solutions with unphysiologically high substrate concentrations.     

Allele and genotype frequencies of polymorphic DCP1, CETP, ADRB2, and HTR2A in the Egyptian population

OBJECTIVE: The goal of this study was to determine the frequencies of important allelic variants of two drug targets, dipeptidyl carboxypeptidase ( DCP1) and cholesteryl ester transfer protein ( CETP), and two other drug receptors, beta-2 adrenergic receptor ( ADRB2) and 5-hydroxy tryptamine 2A receptor ( HTR2A), in the Egyptian population and compare them with the frequencies in other ethnic populations. METHODS: A sensitive real-time polymerase chain reaction assay was developed and successfully applied for genotyping of the consensus (wild-type) alleles plus five variants of four genes: DCP1 [the insertion allele ( I) versus the deletion allele ( D)], CETP*TaqI ( B1 versus B2), ADRB2*R16G, ADRB2*Q27E, and HTR2A*102T>C. This study was carried out in 242 unrelated Egyptian subjects and is the first to describe these allelic variants in the Egyptian population. RESULTS: The frequencies of the tested alleles were found as: DCP1 ( I: D, 0.32:0.68), CETPTaqI ( B1: B2, 0.65:0.35), ADRB2*R16G ( Arg16: Gly16, 0.57:0.43), ADRB2*Q27E ( Gln27: Glu27, 0.76:0.24), and HTR2A*102T>C ( T102: C102, 0.53:0.47). The common Arabian ancestors of the Egyptians, Spanish, Saudi, and Emirate had created a common pattern of distribution of some allelic variants ( DCP1 and CETP). However, in the genotyping of ADRB2, the frequency of the polymorphism at codon 16 was found to be similar to the Chinese population, whereas that at codon 27 was similar to African-Americans with significant differences than other Caucasian populations. The frequency of the HTR2A*102T>C variant appeared to be similar to many Caucasian populations and African-Americans. CONCLUSIONS: We have explored the frequencies of important allelic variants DCP1, CETP, ADRB2, and HTR2A among the Egyptian population focusing on the ethnic diversity in the distribution of the tested mutant alleles. Our results may help in better understanding the observed ethnic variation in angiotensin-converting enzyme inhibition and atherosclerosis therapy. It also may contribute to better characterization of interethnic differences in isoprenaline and clozapine response, which will have implications for the cost effective and rational prescribing of these drugs.