Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress.

BACKGROUND: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. MATERIAL AND METHODS: This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. RESULTS: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. CONCLUSIONS: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

Assessing the hepatoprotective effects of hesperidin on liver-associated disorders in albino rats with experimentally induced obesity and type II diabetes: A histological and biochemical study.

Hesperidin (HSP) has multiple beneficial effects in verities of clinical situations including type 2 diabetes mellitus (T2DM). AIM: Determination of curative effects of HSP on the liver in T2DM rats through biochemical and histopathological studies. METHODS: Animals. Fifty rats were enrolled. 10 rats were fed a normal diet (control group), and the remaining 40 rats received a high-fat diet (HFD) for 8 weeks. The HFD-fed rats were grouped into Group II: 10 rats, and Group III: 10 rats received HSP 100 mg/kg. Group IV: 10 rats received a single dose of streptozotocin (STZ), 30 mg/kg, and Group V: 10 rats received STZ and HSP. Body weight, Blood glucose, insulin level, liver enzymes, lipid profile, oxidative stress, TNF-α, NF-κB, and liver biopsy were estimated. RESULTS: there is improvement in the histological profile of the steatosis in HFD-fed rats treated with HSP either in group III or in group V (received STZ) along with amelioration in blood glucose, insulin, liver enzymes, lipid profile, oxidative profile, TNF-α, and NF-κB. CONCLUSION: HSP in this STZ model revealed an improvement in steatosis, biochemical markers, and histologic findings. By studying these factors, we expected to identify the prospective targets for intervention that could help improve outcomes for individuals with obesity and diabetes-related liver diseases.

Predictors of pulmonary hypertension in patients with hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an immunologically induced inflammation of the lung parenchyma that occurs in susceptible individuals in response to a variety of antigens. Repeated exposures to the causative antigens lead to chronic HP. The condition could be complicated with pulmonary hypertension (PH). METHODOLOGY: 60 patients with established diagnosis of HP were included, clinical examination, high resolution computed tomography (HRCT) of chest, arterial blood gases, six minute walking test (6MWT), desaturation index, spirometry, echocardiography were performed to all patients and right heart catheter was done for patients with high echo probability of PH. RESULTS: The mean age of patients was 41.67 ± 13.4 years with female predominance 83.3% of patients had history of raising birds. 71.7% of cases suffered from resting hypoxia with oxygen saturation 89 ± 11% with desaturation index 9% ± 8%, Echo probability of PH ranged from low to high 71.67, 21.67 and 6.67% respectively, mean pulmonary artery systolic pressure was 63.65 (18.48) mmHg. PH was diagnosed in 17 (28.33%) patients. HP with PH patients were significantly more symptomatic with predominant fibrotic pattern in HRCT chest P < 0.001, 82% of them had hypoxia P < 0.001 with significant desaturation after 6MWT P = 0.001. Predictors of PH in study group were fibrotic pattern in HRCT chest and hypoxia OR = 62.22, P < 0.001; 49.2, P < 0.001 respectively. CONCLUSION: PH was prevalent in 28.33% of patients with HP, predictors of development of PH were fibrotic pattern in HRCT chest and hypoxia. TRIAL REGISTRATION: Retrospectively registered, registration number is NCT05458635, date of registration 07/12/2022.

Egyptian Consensus on the Role of Lung Ultrasonography During the Coronavirus Disease 2019 Pandemic.

Background & Aims: Coronavirus disease 2019 (COVID-19) is a global health problem, presenting with symptoms ranging from mild nonspecific symptoms to serious pneumonia. Early screening techniques are essential in the diagnosis and assessment of disease progression. This consensus was designed to clarify the role of lung ultrasonography versus other imaging modalities in the COVID-19 pandemic. Methods: A multidisciplinary team consisting of experts from different specialties (ie, pulmonary diseases, infectious diseases, intensive care unit and emergency medicine, radiology, and public health) who deal with patients with COVID-19 from different geographical areas was classified into task groups to review the literatures from different databases and generate 10 statements. The final consensus statements were based on expert physically panelists' discussion held in Cairo July 2021 followed by electric voting for each statement. Results: The statements were electronically voted to be either "agree," "not agree," or "neutral." For a statement to be accepted to the consensus, it should have 80% agreement. Conclusion: Lung ultrasonography is a rapid and useful tool, which can be performed at bedside and overcomes computed tomography limitations, for screening and monitoring patients with COVID-19 with an accepted accuracy rate.

Clinical evaluation of pregnant women with SARS-COV2 pneumonia: a real-life study from Egypt.

BACKGROUND: Knowledge about the outcome of COVID-19 on pregnant women is so important. The published literature on the outcomes of pregnant women with COVID-19 is confusing. The aim of this study was to report our clinical experience about the effect of COVID-19 on pregnant women and to determine whether it was associated with increased mortality or an increase in the need for mechanical ventilation in this special category of patients. METHODS: This was a cohort study from some isolation hospitals of the Ministry of Health and Population, in eleven governorates, Egypt. The clinical data from the first 64 pregnant women with COVID-19 whose care was managed at some of the Egyptian hospitals from 14 March to 14 June 2020 as well as 114 non-pregnant women with COVID-19 was reviewed. RESULTS: The two groups did not show any significant difference regarding the main outcomes of the disease. Two cases in each group needed mechanical ventilation (p 0.617). Three cases (4.7%) died among the pregnant women and two (1.8%) died among the non-pregnant women (p 0.352). CONCLUSIONS: The main clinical outcomes of COVID-19 were not different between pregnant and non-pregnant women with COVID-19. Based on our findings, pregnancy did not exacerbate the course or mortality of COVID-19 pneumonia.

Utility of Lung Ultrasound in Decision-making to Prioritize Hospital Admission for COVID-19 Patients: A Developing Country Perspective.

BACKGROUND AND AIMS: In the midst of this pandemic, planning the prioritization of hospital admissions for patients affected with COVID-19 should be of prime concern, particularly in healthcare settings with limited resources. Thus, in this study, we aimed to develop a novel approach to triage COVID-19 patients and attempt to prioritize their hospital admission using Lung Ultrasonography (LUS). The efficacy of LUS in triaging suspected COVID-19 patients and assessing the severity of COVID-19 pneumonia was evaluated; the findings were then compared with those obtained by chest computed tomography (CT). METHODS: This multicenter, cross-sectional study comprised 243 COVID-19 patients who presented to the emergency department in 3 major university hospitals in Egypt. LUS was performed by an experienced emergency or chest physician, according to the local protocol of each hospital. Demographic, clinical, and laboratory data were then collected from each patient. Each patient was subjected to chest CT scans and LUS. RESULTS: The mean age of the 243 patients was 46.7 ± 10.4 years. Ground-glass opacity, subpleural consolidation, translobar consolidation, and crazy paving were reported in the chest CT scans of 54.3%, 15.2%, 11.1%, and 8.6% of the patients, respectively. B-line artifacts were observed in 81.1% of the patients (confluent pattern, 18.9%). The LUS findings completely coincided with the CT findings (Kappa agreement value, 0.77) in 197 patients (81.1%) and offered a diagnostic sensitivity of 74%, diagnostic specificity of 97.9%, positive predictive value of 90.2%, and negative predictive value of 93.6% for the COVID-19 patients. Following the addition of O2 saturation to the lung imaging findings, the ultrasound method was able to demonstrate 100% sensitivity and specificity in accurately differentiating between severe and non-severe lung diseases. CONCLUSION: LUS with oxygen saturation might prove to be effective in prioritizing the hospital admission of COVID-19 patients, particularly in healthcare settings with limited resources.

A highly sensitive fluorimetric protocol based on isoindole formation for determination of gabapentin.

A new, simple, highly sensitive and selective spectrofluorimetric method was developed for determination of gabapentin through its derivatization with o-phthalaldehyde in the presence of 2-mercaptoethanol. The resulting product was highly fluorescent and its emission intensity was measured at 431 nm after excitation at 335 nm. The effect of different experimental parameters on the formation and stability of the fluorescent product was carefully studied and optimized. The fluorescence-concentration plot was rectilinear over the range of 25-125 ng mL-1. The lower detection and quantification limits were 3.4 mL-1 and 11.2 ng mL-1, respectively. The procedure was fully validated according to the guidelines of the International Conference on Harmonization. The proposed method was successfully applied for the determination of the investigated drug in its pharmaceutical capsules and the results were in agreement with those of the reported method, in terms of the accuracy and precision. The low cost of analysis and high sensitivity make the proposed method ideally suited for analysis of the investigated drug in quality control laboratories.

Interleukin-17 Gene Expression and Serum Levels in AsthmaDegenerative Model.

Asthma is one of the most common chronic respiratory diseases. It is associated with significant morbidity and shows an increasing prevalence over time. Accumulating evidence suggests that interleukin (IL)-17 has a key role in severe asthma. The aim of the study was to determine quantitatively gene expression of IL-17 in peripheral blood mononuclear cells (PBMN) & the level of IL-17 in the serum of asthmatic patients, to correlate the level of IL-17 with the severity of asthma and to compare between gene expression of IL-17 and its serum level. Forty (40) asthmatic patients were enrolled and subdivided into 2 subgroups; controlled & uncontrolled asthma according to GINA, 2014. In addition, twenty (20) healthy control subjects were included. Blood samples were subjected to real time PCR assays for IL-17 mRNA gene expression and serum was tested by ELISA for estimation of IL-17 serum levels. Significant higher serum IL-17 levels were found in patients with uncontrolled asthma compared to patients with controlled asthma and healthy control group. Mean serum IL-17 value was 87.24 pg/ml in uncontrolled asthma, 75.9 pg/ml in controlled asthma and 47.0 pg/ml in healthy group (P= 0.00). IL-17 mRNA gene expression levels (ΔΔ Ct) were also significantly elevated in uncontrolled asthma compared to patients with controlled asthma and healthy control group. Mean IL-17 mRNA gene expression levels were 33.7 units in uncontrolled asthma, 7.0 in controlled asthma and 0.30 in healthy group (P=0.00).

Development of spectrofluorimetric method for determination of certain antiepileptic drugs through condensation with ninhydrin and phenyl acetaldehyde.

A new and simple spectrofluorimetric method was developed and validated for determination of gabapentin and pregabalin in their pure forms and pharmaceutical formulations with high sensitivity and selectivity. The proposed method was based on the formation of fluorescent products as a result of condensation reaction of investigated drugs with ninhydrin and phenyl acetaldehyde in Teorell and Stenhagen buffer medium. The fluorescent products had emission maxima at 470 nm after excitation at 375 nm. Parameters affecting the progress of the reaction and stability of the formed products were carefully investigated individually and optimized. The fluorescence-concentration plots were rectilinear over the range of 5.0-25.0 µg ml-1 for gabapentin and 2.0-30.0 µg ml-1 for pregabalin with excellent correlation coefficients (0.9999 for gabapentin and pregabalin). The lower detection limits were 0.45 and 0.19 µg ml-1 for gabapentin and pregabalin, respectively. The developed method has been validated in respect to linearity, accuracy, precision, selectivity and sensitivity. In addition, the proposed method was further applied for quantitative analysis of drugs in their pharmaceutical formulations with high degree of accuracy and precision. The obtained results had an excellent agreement with the reference method, indicating no significant difference in accuracy and precision.

Evaluation of Percutaneous Tibial Nerve Stimulation for Treatment of Refractory Painful Bladder Syndrome.

OBJECTIVE: To evaluate the efficacy of intermittent percutaneous tibial nerve stimulation (PTNS) as a treatment modality for patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS). PATIENTS AND METHODS: Twenty female patients with IC/BPS (mean symptom duration of 4.5 ± 2.4 years) each had a 30-minute session of PTNS per week for 12 successive weeks and the symptoms were assessed before, during, and after the treatment sessions by voiding diary, visual analog scale (VAS) for pain, interstitial cystitis symptom and problem indices (ICSI and ICPI), and global response assessment (GRA) scale. The scores of the previous questionnaires were evaluated at weeks 0, 6, and 12. RESULTS: At week 0, the VAS, day time frequency, nocturia, and average voiding volume were 5.6 ± 1.1, 14.5 ± 4.0, 3.0 ± 0.9, and 131.8 ± 35.3 mL, respectively, meanwhile at week 12 these scores were 5.2 ± 1.5, 12.15 ± 3.7, 2.6 ± 0.7, and 141.0 ± 36.2, respectively. There was no statistically significant difference between the scores of the ICPI between weeks 0, 6, and 12 (P = .937). As regards the GRA score after the 12th session, 17 patients (85%) reported having no effect, 1 patient (5%) reported as having worse symptoms, and 2 patients (10%) reported having a mild good response. CONCLUSION: Intermittent PTNS is not a satisfactory treatment for refractory IC/BPS. However, it is recommended to perform more studies with other treatment protocol (maybe closer sessions) to confirm these results.