Hydrophilic catheters for intermittent catheterization and occurrence of urinary tract infections. A retrospective comparative study in patients with spinal cord Injury.

BACKGROUND: Neurogenic bladder dysfunction is a major problem for spinal cord injury (SCI) patients not only due to the risk of serious complications but also because of the impact on quality of life. The main aim of this study is to compare the rate of urinary tract infection (UTI) associated with hydrophilic-coated catheters versus uncoated polyvinyl chloride (PVC) catheters among SCI patients presenting with functional neurogenic bladder sphincter disorders. METHODOLOGY: This was a retrospective cohort study from 2005 to 2020 including adult male or female patients who have an SCI at least more than 1 month ago with neurogenic bladder dysfunction and were using intermittent catheterization (single-use hydrophilic-coated or the standard-of-care polyvinyl chloride uncoated standard catheters) at least 3 times a day to maintain bladder emptying. RESULTS: A total of 1000 patients were selected and recruited through a stratified random sampling technique with 467 (47.60%) patients in the uncoated catheter arm and 524 (52.60%) in the coated catheter groups. The three outcome measures, namely: symptomatic UTI, Bacteriuria, and pyuria were significantly higher in the group using uncoated polyvinyl chloride (PVC) catheters compared to hydrophilic-coated catheters at the rate of 79.60% vs.46.60%, 81.10% vs. 64.69, and 53.57% versus 41.79% respectively. Males, elder patients, longer duration, and severity of SCI were associated with increased risk of symptomatic UTI. CONCLUSIONS: The results indicate a beneficial effect regarding clinical UTI when using hydrophilic-coated catheters in terms of fewer cases of symptomatic UTI. Bacteriuria is inevitable in patients with long-term catheterization, however, treatment should not be started unless the clinical symptoms exist. More attention should be given to the high-risk group for symptomatic UTIs.

Galantamine mitigates testicular injury and disturbed spermatogenesis in adjuvant arthritic rats via modulating apoptosis, inflammatory signals, and IL-6/JAK/STAT3/SOCS3 signaling.

Rheumatoid arthritis (RA) affects the joints and the endocrine system via persistent immune system activation. RA patients have a higher frequency of testicular dysfunction, impotence, and decreased libido. This investigation aimed to evaluate the efficacy of galantamine (GAL) on testicular injury secondary to RA. Rats were allocated into four groups: control, GAL (2 mg/kg/day, p.o), CFA (0.3 mg/kg, s.c), and CFA + GAL. Testicular injury indicators, such as testosterone level, sperm count, and gonadosomatic index, were evaluated. Inflammatory indicators, such as interleukin-6 (IL-6), p-Nuclear factor kappa B (NF-κB p65), and anti-inflammatory cytokine interleukin-10 (IL-10), were assessed. Cleaved caspase-3 expression was immunohistochemically investigated. Protein expressions of Janus kinase (JAK), signal transducers and activators of transcription (STAT3), and Suppressors of Cytokine Signaling 3 (SOCS3) were examined by Western blot analysis. Results show that serum testosterone, sperm count, and gonadosomatic index were increased significantly by GAL. Additionally, GAL significantly diminished testicular IL-6 while improved IL-10 expression relative to CFA group. Furthermore, GAL attenuated testicular histopathological abnormalities by CFA and downregulated cleaved caspase-3 and NF-κB p65 expressions. It also downregulated JAK/STAT3 cascade with SOCS3 upregulation. In conclusion, GAL has potential protective effects on testicular damage secondary to RA via counteracting testicular inflammation, apoptosis, and inhibiting IL-6/JAK/STAT3/SOCS3 signaling.

Effect of an antimicrobial stewardship program in the prevention of antibiotic misuse in patients with spinal cord injury undergoing minor urologic procedures: a single-group, quasi-experiment study.

BACKGROUND: Antimicrobial stewardship programs (ASPs) are an internationally recognized strategy for reducing antimicrobial resistance while maintaining patient safety. ASP activities include the restriction of broad-spectrum antibiotics, the establishment of hospital guidelines based on antibiograms, and the promotion of appropriate antibiotic use. This study aimed to determine whether the implementation of antimicrobial stewardship practices improved the effects of a peri-procedure antibiotic prophylaxis prescribed by urologists for patients with spinal cord injury/disease (SCI/D) undergoing minor urological procedures at a tertiary care hospital. METHODS: This single-group, quasi-experiment study included adult patients with SCI/D who required minor urological procedures (cystoscopy, cytobotox, cystolitholapaxy, and urodynamic study) and who were hospitalized between 2012 and 2020. RESULTS: In total, 233 patients were included in each of the pre- and post-ASP implantation groups. There was a significant reduction in antibiotic use among patients who received a pre-procedure antimicrobial prophylaxis in the post- compared to the pre-implementation group (45.9% vs. 24.46%, p < 0.0001), and there was a highly significant reduction in the post- compared to the pre-implementation group in the number who received a post-procedure prophylaxis (16.7% vs. 1.2%, p < 0.0001). CONCLUSION: ASP implementation is a highly effective strategy for reducing the use of peri-procedure antimicrobial prophylaxes in patients with SCI/D injuries undergoing minor urological procedures.

Novel therapeutic modalities target cell signaling of Renin-Angiotensin system/NF-κB-induced cell cycle arrest and apoptosis in urethane-induced lung cancer in mice: An in vivo study.

BACKGROUND: Lung cancer has risen to the top of the list of cancer-related deaths worldwide. Aliskiren is a direct renin inhibitor. AIM: This study aims to investigate the impact of cell signaling of Renin-Angiotensin system (RAS)/NF-κB on lung cancer by investigating the potential therapeutic effects of aliskiren for lung cancer treatment in urethane-induced lung cancer in mice. METHODS: Male BALB/c mice were randomly assigned to one of five treatment groups for 150 days, including (1) normal control; (2) aliskiren (25 mg/kg/i.p) daily, (3) urethane at a dose of 1.5 g/kg (i.p) at Day 1 and 60 (nonsmall cell lung cancer[NSCLC] group) (4) NSCLC mice received carboplatin (15 mg/kg/i.p) every other day for the last 4 successive weeks and (5) NSCLC mice treated with aliskiren daily. Tumor size was determined based on blood sampling, and lungs were isolated for biochemical analysis, western blot analysis assay, and histopathological examination. RESULTS: Urethane demonstrated significant changes in all biochemical and molecular parameters and histological patterns. Aliskiren-treated mice had significantly lower levels of NF-κB p65, Bcl-2, cyclin D1, ICAM-1, MMP-2, and Nrf2, with an increase in the catalytic activity of caspase-3 due to its RAS inhibitory mechanism. The combined urethane administration with aliskiren demonstrated a significant improvement in the histopathological examination. CONCLUSION: RAS/NF-B cell signaling is a potential therapeutic target for preventing and treating lung adenocarcinoma, evidenced by the fundamental cytotoxic mechanism and attenuation of metastasis and angiogenesis induced by the treatment of NSCLC mice with aliskiren.

The modulatory effects of cinnamaldehyde on uric acid level and IL-6/JAK1/STAT3 signaling as a promising therapeutic strategy against benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a widespread disorder in elderly men. Cinnamaldehyde, which is a major constituent in the essential oil of cinnamon, has been previously reported to reduce xanthine oxidase activity, in addition to its anti-inflammatory, anti-oxidant, and anti-proliferative activities. Our study was designed to investigate the potential modulatory effects of cinnamaldehyde on testosterone model of BPH in rats through reduction of uric acid level, and suppression of IL-6/JAK1/STAT3 signaling pathway. Cinnamaldehyde (40 and 75 mg/kg) was orally administered to male Wistar rats for 3 weeks, and concurrently with testosterone (3 mg/kg, s.c.) from the second week. Cinnamaldehyde ameliorated the elevation in prostatic weight and index compared to rats treated with testosterone only, that was also confirmed by alleviation of histopathological changes in prostate architecture. The protective mechanisms of cinnamaldehyde were elucidated through inhibition of xanthine oxidase activity and reduced uric acid level. That was accompanied by reduction of the pro-inflammatory cytokines; interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-alpha (TNF-α), and the nuclear translocation of the transcription factor NF-κB p65, that could be attributed also to the enhanced anti-oxidant defense by cinnamaldehyde. The protein expression of JAK1, which is IL-6 receptor linked protein, was reduced with subsequently reduced activation of STAT3 protein. That eventually suppressed the formation of the proliferation protein cyclin D1, while elevated Bax/Bcl2 ratio. It can be concluded that reducing uric acid level through xanthine oxidase inhibition and suppression of the inflammatory signaling cascade; IL-6/JAK1/STAT3; by cinnamaldehyde could be a novel and promising therapeutic approach against BPH.

The potential hepatoprotective effects of lovastatin combined with oral hypoglycemic agents in streptozotocin-induced diabetes in rats.

Aims: Epidemiologic studies have shown that individuals with diabetes have a higher risk of hepatic diseases which represent a true clinical problem. The purpose of the present study was to assess the possible modulatory effect of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin on therapeutic efficiency of traditional antidiabetics, as metformin and gliclazide, regarding hepatic complications in streptozotocin (STZ)-induced diabetes in rats.Methods: Animals were divided into seven groups; normal control group, STZ control group (50 mg/kg, i.p., single dose), lovastatin group, metformin group, gliclazide group, lovastatin plus metformin group and lovastatin plus gliclazide group. Serum HMG-CoA reductase, in addition to serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) as hepatocyte integrity loss markers, hepatic tissue thiobarbituric acid reactive substances (TBARS), glutathione reduced (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase as oxidative stress markers, as well as serum tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) and hepatic nitric oxide end products (NOx) as inflammatory markers were assessed, coupled with a confirmatory histopathological study.Results: The combined effect of lovastatin with metformin or gliclazide was significantly better than either drug alone regarding serum AST, ALP and TNF-α, and hepatic TBARS, GSH, GST, SOD and NOx levels.Conclusions: Hepatic complications associated with diabetes could be improved by combination of metformin or gliclazide with lovastatin.

Perindopril ameliorates experimental Alzheimer's disease progression: role of amyloid ß degradation, central estrogen receptor and hyperlipidemic-lipid raft signaling.

Accumulating evidence indicates that over-stimulation of angiotensin-converting enzyme 1 (ACE1) activity is associated with ß-amyloid (Aß) and phosphorylated tau (p-tau)-induced apoptosis, oxido-nitrosative neuroinflammatory stress and neurodegeneration in Alzheimer's disease (AD). Alternatively, activation of the ACE2, the metalloprotease neprilysin (Neutral Endopeptidase; NEP) and the insulin-degrading enzyme (IDE) could oppose the effects of ACE1 activation. We aim to investigate the relationship between ACE1/ACE2/NEP/IDE and amyloidogenic/hyperlipidemic-lipid raft signaling in hyperlipidemic AD model. Induction of AD was performed in ovariectomized female rats with high-fat high fructose diet (HFFD) feeding after 4 weeks following D-galactose injection (150 mg/kg). The brain-penetrating ACE1 inhibitor perindopril (0.5 mg/kg/day, p.o.) was administered on a daily basis for 30 days. Perindopril significantly decreased hippocampal expression of ACE1 and increased expression of ACE2, NEP and IDE. Perindopril markedly decreased Aß1-42, improved lipid profile and ameliorated the lipid raft protein markers caveolin1 (CAV1) and flotillin 1 (FLOT1). This was accompanied by decreased expression of p-tau and enhancement of cholinergic neurotransmission, coupled with decreased oxido-nitrosative neuroinflammatory stress, enhancement of blood-brain barrier (BBB) functioning and lower expression of the apoptotic markers glial fibrillary acidic protein (GFAP), Bax and ß-tubulin. In addition, perindopril ameliorated histopathological damage and improved learning, cognitive and recognition impairment as well as depressive behavior in Morris water maze, Y maze, novel object recognition and forced swimming tests, respectively. Conclusively, perindopril could improve cognitive defects in AD rats, at least through activation of ACE2/NEP/IDE and inhibition of ACE1 and subsequent modulation of amyloidogenic/hyperlipidemic-lipid raft signaling and oxido-nitrosative stress.

Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways.

Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property.

Amlodipine alleviates cisplatin-induced nephrotoxicity in rats through gamma-glutamyl transpeptidase (GGT) enzyme inhibition, associated with regulation of Nrf2/HO-1, MAPK/NF-κB, and Bax/Bcl-2 signaling.

BACKGROUND: The therapeutic utility of the effective chemotherapeutic agent cisplatin is hampered by its nephrotoxic effect. We aimed from the current study to examine the possible protective effects of amlodipine through gamma-glutamyl transpeptidase (GGT) enzyme inhibition against cisplatin nephrotoxicity. METHODS: Amlodipine (5 mg/kg, po) was administered to rats for 14 successive days. On the 10th day, nephrotoxicity was induced by a single dose of cisplatin (6.5 mg/kg, ip). On the last day, blood samples were collected for estimation of kidney function, while kidney samples were used for determination of GGT activity, oxidative stress, inflammatory, and apoptotic markers, along with histopathological evaluation. RESULTS: Amlodipine alleviated renal injury that was manifested by significantly diminished serum creatinine and blood urea nitrogen levels, compared to cisplatin group. Amlodipine inhibited GGT enzyme, which participates in the metabolism of extracellular glutathione (GSH) and platinum-GSH-conjugates to a reactive toxic thiol. Besides, amlodipine diminished mRNA expression of NADPH oxidase in the kidney, while enhanced the anti-oxidant defense by activating Nrf2/HO-1 signaling. Additionally, it showed marked anti-inflammatory response by reducing expressions of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB), with subsequent down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1). Moreover, amlodipine reduced Bax/Bcl-2 ratio and elevated hepatocyte growth factor (HGF), thus favoring renal cell survival. CONCLUSIONS: Effective GGT inhibition by amlodipine associated with enhancement of anti-oxidant defense and suppression of inflammatory signaling and apoptosis support our suggestion that amlodipine could replace toxic GGT inhibitors in protection against cisplatin nephrotoxicity.

Physicians' choices in the first- and second-line management of type 2 diabetes in the Kingdom of Saudi Arabia.

OBJECTIVES: The DISCOVER study is a global, prospective, three- year- observational (non-interventional) study that was conducted in 37 countries throughout the world including Saudi Arabia and aimed to assess variations in treatment patterns and therapeutic outcomes in type 2 diabetic patients. The current manuscript is reporting data of DISCOVER study across different health sectors of various provinces in the Kingdom of Saudi Arabia. METHODS: In this study, 519 Saudi type 2 diabetics, non-insulin users, aged 18 years or older, initiating second line therapy, were selected from nine health institutes, in four out of five provinces in Saudi Arabia. Data was collected at baseline (initiation of 2nd line therapy) by the treating physician using an electronic case report form (eCRF) via a web-based data capture system. Each selected subject was asked to complete four self-administered questionnaires. RESULTS: The mean age of the studied population was 52.4 ± 11 years. Among the subjects selected from the nine medical centers, 55% were men, with almost 65% between the ages of 46 and 65 years. The oral agent used as 1st line in the majority of patients was metformin, prescribed in 89.2% of the study cohort. In the second line, sitagliptin was the most frequently used, at 61.8%. followed by gliclazide, glibenclamide, and glimepiride at 35.6%, 13.1%, and 12.7%, respectively. CONCLUSION: Metformin, with or without sulfonylureas, is the most commonly prescribed first-line treatment for patients with type 2 diabetes, managed either in governmental institutions, or in the private sector. The most common second line drugs were DPP4 inhibitors, mainly sitagliptin, followed by the third and second generation of sulfonylureas. Drug affordability was not an issue, since the vast majority of the patients received medication free of charge.

Antidiabetic and antioxidant effects of tannic acid and melatonin on streptozotocin induced diabetes in rats.

The present investigation aimed to study the possible antidiabetic and related antioxidant potentials of tannic acid and melatonin in streptozotocin (STZ) induced diabetes in rats. Four groups of rats received intraperitoneal one dose of 50mg/kg body weight STZ for the induction of diabetes. The first group served as diabetic control group and received the vehicle. Four days after induction of diabetes, the remaining three groups received glibenclamide (6mg/kg/day), tannic acid (1 g/kg/day) and melatonin (10 mg/kg/day) for two weeks. A fifth group served as vehicle control group. At the end of the experimental period, blood samples and liver samples were collected for the determination of diabetes correlated biomarkers. Treatment of diabetic rats with tannic acid or melatonin attenuated most of the changes associated with STZ induced diabetes. The present results evidenced the beneficial effects of tannic acid and melatonin in diabetes management.

Protective effects of vitamin D and losartan in complete Freund's adjuvant-induced arthritis in rats.

The current study was designed to explore the protecting effects of vitamin D and losartan in treatment of rheumatoid arthritis (RA). Animals were allotted to five groups: Group I received vehicles only (vehicle control). Group II was administered complete Freund's adjuvant (CFA) and did not receive any medication. The remaining three groups (III, IV, V) were given CFA followed by treatment with leflunomide, vitamin D or losartan, respectively for two weeks. Compelling increment in tumor necrosis factor (TNF-α), interleukin 6 (IL-6), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), malondialdehyde (MDA) level, white blood cells (WBCs), total cholesterol (TC) and triglycerides (TGs) was revealed in arthritic rats. This was associated with marked decline in glutathione (GSH) level, red blood cells (RBCs), hemoglobin (Hb), Platelets (Plts), hematocrit (Hct) and high density lipoprotein cholesterol (HDL). vitamin D or losartan significantly decreased TNF α, IL-6, RF, ESR, MDA, TC, TGs, WBCs and significantly increased RBCs, Hb, Hct, Plts and HDL. It could be concluded that vitamin D and losartan are able to repress the alterations associated with adjuvant-induced arthritis (AIA). This preserving effect might be partially attributed to antiarithritic, hypolipidemic and antianemic properties.

ASSESSMENT OF KNOWLEDGE, ATTITUDE AND PRACTICE TOWARDS CONSANGUINEOUS MARRIAGES AMONG A COHORT OF MULTIETHNIC HEALTH CARE PROVIDERS IN SAUDI ARABIA.

This study aimed to assess knowledge, attitude and practice related to consanguinity among multiethnic health care providers in the Kingdom of Saudi Arabia. Using a cross-sectional study design, a validated, self-administered close-ended questionnaire was randomly distributed to health care providers in different health institutions in the country between 1st August 2012 and 31st July 2013. A total of 1235 health care providers completed the study questionnaire. Of the 892 married participants (72.23% of total), 11.43% were married to a first cousin, and were predominantly Arabs, younger than 40 years and male. Only 17.80% of the patients seen by the health care providers requested consanguinity related counselling. A knowledge barrier was expressed by 27.49% of the participants, and 85.67% indicated their willingness to have more training in basic genetic counselling. A language barrier was expressed as a limiting factor to counselling for consanguinity among non-Arabs. The health care providers had a major dearth of knowledge that was reflected in their attitude and practice towards consanguinity counselling. This finding indicates the need for more undergraduate and postgraduate medical and nursing education and training in the counselling of consanguineous couples. It is recommended that consanguinity counselling is included in the current premarital screening and counselling programmes in the Kingdom.

Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation.

Cisplatin (CP) is one of the most effective chemotherapeutic agents. Unfortunately, CP-induced nephrotoxicity hampered its use. This study aims to investigate the effect of vitamin E (Vit E) on CP-induced nephrotoxicity. Male white albino rats were divided to four group's six rats each and received either, 1% tween 80 in normal saline or Vit E (75 mg/kg) per day for 14 consecutive days or a single injection of CP (6 mg/kg) alone or CP (6 mg/kg) together with Vit E (75 mg/kg per day for 14 consecutive days). Five days after the CP injection, rats were euthanized; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly increased serum levels of creatinine and urea. Moreover, reduced glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities were significantly reduced with concurrent increase in kidney malondialdehyde (MDA) content following CP treatment. Vit E successfully lowered serum levels of urea and creatinine, enhanced creatinine clearance and diuresis, and normalized relative kidney/body weight. Furthermore, Vit E successfully normalized renal MDA and nitrite concentrations, elevated GSH level, and restored CAT and SOD activities in renal tissues. Histopathological examination of rat kidney revealed that Vit E significantly mitigated CP-induced renal damage. Importantly, administration of Vit E reduced kidney total platinum concentration indicating a role of platinum renal accumulation on the ability of Vit E to protect against CP nephrotoxicity.

Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor.

Angiotensin II has pro-inflammatory and pro-oxidant potentials. We investigated the possible protective effects of the Angiotensin II receptor blocker telmisartan, compared with the superoxide scavenger tempol, on lipopolysaccharide (LPS)-induced cognitive decline and amyloidogenesis. Briefly, mice were allocated into a normal control group, an LPS control group, a tempol treatment group, and 2 telmisartan treatment groups. A behavioral study was conducted followed by a biochemical study via assessment of brain levels of beta amyloid (Aß) and brain-derived neurotropic factor (BDNF) as amyloidogenesis and neuroplasticity markers, tumor necrosis factor alpha (TNF-α), nitric oxide end products (NOx), neuronal and inducible nitric oxide synthase (nNOS and iNOS) as inflammatory markers, and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using routine and special Congo red stains. Tempol and telmisartan improved cognition, decreased brain Aß deposition and BDNF depletion, decreased TNF-α, NOx, nNOS, iNOS, MDA, and NT brain levels, and increased brain SOD and GSH contents, parallel to confirmatory histopathological evidences. In conclusion, tempol and telmisartan are promising drugs in managing cognitive impairment and amyloidogenesis, at least via upregulation of BDNF with inhibition of neuroinflammation and oxido-nitrosative stress.

Leaves of Cordia boissieri A. DC. as a potential source of bioactive secondary metabolites for protection against metabolic syndrome-induced in rats.

Cordia boissieri A. DC. (Boraginaceae) is traditionally used as an herbal remedy for diabetes by Hispanic women in Southwestern USA. A recent investigation showed the significant protective effect of ethyl acetate extract against metabolic syndrome (MS). However, the corresponding active principles responsible for this effect and relations between their structure and biological actions remain unclear. Thus, ethyl acetate extract was subjected to column chromatography, which yielded seven compounds identified on the basis of spectroscopic data as rutin, hesperidin, kaempferol-3-O-ß-d-glucopyranoside, rosmarinic acid, ß-sitosterol-3-O-ß-d-glucopyranoside, quercetin, and kaempferol. The isolated compounds (5 mg/kg/day) were tested in a fructose enriched-diet rat model using metformin as a standard drug. Blood samples were withdrawn for estimation of MS-associated biomarkers and liver samples were subjected to histopathological and immunohistochemical examination. The isolated compounds impaired most of the changes associated with MS as evidenced by improved insulin sensitivity, glucose tolerance, kidney function, lipid profiles and reduced oxidative stress and inflammation by different degrees. It is worth noting that quercetin and kaempferol showed the most potent effect. Structure-activity relationship study revealed that the presence of 2,3-double bond in ring C and ortho-hydroxylation in ring B increases the flavonoids activity while glycosylation or methylation decreased this activity.

Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice.

CONTEXT: Currently, the outcomes of the use of cisplatin in cancer therapy is limited by nephrotoxicity. OBJECTIVE: This study aims to investigate the nephroprotective role of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. MATERIALS AND METHODS: Adult female Wistar Albino mice were divided into eight groups (n = 8). Group I served as normal control. Groups II, III and IV received apigenin (3 mg/kg, i.p.), myricetin (3 mg/kg, i.p.) or their combination respectively, for seven days. Group V served as positive control group, received vehicles for seven days and cisplatin (7.5 mg/kg, i.p.) for three days starting at day five. Groups VI, VII and VIII received apigenin, myricetin or their combination, respectively for seven days as well as cisplatin injection for three days starting at day five. by the end of the experimental period, a biochemical study involving, nephrotoxicity markers [serum creatinine (Cr) and blood urea nitrogen (BUN)], apoptotic marker [caspase 3], inflammatory mediators [tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase I and II (COXI, COXII)] and oxidative stress biomarkers [malondialdehyde (MDA), reduced glutathione (GSH) and catalase] was conducted. In addition, renal histopathological alterations were evaluated. RESULTS: Apigenin, myricetin and their combination significantly reduced blood BUN, serum Cr, caspase-3TNF-α, IL-6, COXI and COXII, MDA levels and significantly increased GSH level and catalase activity parallel to, histopathological improvement in kidney tissues. DISCUSSION AND CONCLUSION: Apigenin and myricetin exhibited a protective and promising preventive strategy against cisplatin-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.

Assessment of the prevalence and risk factors of ophthalmoplegia among diabetic patients in a large national diabetes registry cohort.

BACKGROUND: There are limited data on the epidemiology and risk factors of ophthalmoplegia among diabetic patients. This study aims to determine the prevalence and important risk factors related to ophthalmoplegia among diabetic patients. METHODS: This is an observational registry-based study using the Saudi National Diabetes Registry (SNDR) database to select diabetic patients regardless of their diabetes type. A total of 64,351 Saudi diabetic patients aged more than 18 years and registered in SNDR between January 2000 and December 2010 were analyzed to identify ophthalmoplegic cases. Demographic, clinical, and biochemical parameters were studied and STROBE guidelines were used to design and report the results of this study. RESULTS: The overall prevalence of ophthalmoplegia cases was 0.32 %, further distributed into: 53.11 %, 36.36 %, and 2.8 % for cranial nerves VI, III, IV palsies respectively. Ophthalmoplegic cases were predominantly type 2 diabetic males with older age and longer diabetes duration. The most important and significant risk factors were age ≥ 45 years, diabetes duration ≥ 10 years, male gender and presence of retinopathy and nephropathy. CONCLUSIONS: Ophthalmoplegia is a rare entity associated mainly with type 2 diabetes. Clinicians have to consider its risk factors when screening or planning for prevention of this condition.

Predicting COVID-19 outcomes with the Edmonton Obesity Staging System.

BACKGROUND: Multiple studies have demonstrated a correlation between a high body mass index and discriminatory COVID-19 outcomes. Studies appear to indicate that there is a correlation between obesity-related comorbidities and less favorable outcomes. OBJECTIVES: The primary aim of the current investigation is to conduct a thorough assessment of the correlation between BMI and comorbidities associated with obesity, and their potential impact on the severity and consequences of COVID-19 infection among patients receiving care in a tertiary healthcare setting. DESIGN: Retrospective cohort. SETTINGS: Tertiary rehabilitation center, Riyadh, Saudi Arabia. PATIENTS AND METHODS: The study included all individuals who received medical treatment and tested positive for COVID-19 by means of RT-PCR during the period from March to September 2020. COVID-19 patients were classified using Edmonton Obesity Staging System (EOSS). MAIN OUTCOME MEASURES: COVID-19-related complications, including pneumonia and cytokine release syndrome, as well as the time length to COVID-19 negativization. SAMPLE SIZE: 315 patients. RESULTS: The median (25th-75th percentiles) age of the patients was 38 (31.5-49) years old. Males outnumbered females, and 66% of patients were non-Saudis. Forty-eight patients (15.2%) had obesity class I, whereas 13 patients (4.1%) had class II. Thirty-two patients (10.2%) were classified as EOSS stage 1, 105 patients (33.3%) were classified as EOSS stage 2, and 25 patients (7.9%) were assigned to EOSS stage 3. Males predominated in EOSS stages 1 and 2, whereas females predominated in stage 3. In EOSS stage 3, 52% of cases had moderate severity and 48% had severe illness. CONCLUSIONS: EOSS distinguishes the COVID-19 risks of poor outcomes beyond BMI. Patients who were overweight or obese but remained in the stage 1 of the EOSS had a lower risk of a poor COVID-19 outome than normal-weight patients. The health status of obese patients is a more precise indicator of the progression of COVID-19 during hospitalization than BMI alone. LIMITATIONS: Given the limited capacity of urgent care facilities to conduct a comprehensive evaluation of comorbidities and other relevant outcomes in all patients, it is plausible that certain patients may have been erroneously classified with an EOSS stage 2 diagnosis, when in fact they ought to have been assigned a stage 3 diagnosis.

The enteroprotective effect of nifuroxazide against methotrexate-induced intestinal injury involves co-activation of PPAR-γ, SIRT1, Nrf2, and suppression of NF-κB and JAK1/STAT3 signals.

Methotrexate (MTX) has long manifested therapeutic efficacy in several neoplastic and autoimmune disorders. However, MTX-associated intestinal toxicity restricts the continuation of treatment. Nifuroxazide (NIF) is an oral antibiotic approved for gastrointestinal infections as an effective antidiarrheal agent with a high safety profile. The current study was designed to explore the potential efficacy of NIF in alleviating intestinal toxicity associated with MTX chemotherapy with the elucidation of the proposed molecular mechanisms. Rats were administered NIF (50 mg/kg; p.o.) for ten days. On day five, a single i.p. injection of MTX (20 mg/kg) was given to induce intestinal intoxication. At the end of the experiment, duodenal tissue samples were isolated for biochemical, Western blotting, immunohistochemical (IHC), and histopathological analysis via H&E, PSA, and Alcian blue stains. NIF showed antioxidant enteroprotective effects against MTX intestinal intoxication through enhanced expression of the redox-sensitive signals of PPAR-γ, SIRT1, and Nrf2 estimated by IHC. Moreover, NIF down-regulated the pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6), NF-κB protein expression, and the phosphorylation of JAK1/STAT3 proteins, leading to mitigation of intestinal inflammation. In accordance, the histological investigation revealed that NIF ameliorated the intestinal pathological changes, preserved the goblet cells, and reduced the inflammatory cells infiltration. Therefore, NIF could be a promising candidate for adjunctive therapy with MTX to mitigate the associated intestinal injury and increase its tolerability.